McArdle Disease And Related Glycogen

Storage Disorders

Highly specialized National Service

Ros Quinlivan

Taunton 2018

Muscle glycogen metabolism disorders

Fixed muscle weakness

GSDII

Pompe Disease

GSDIII

GSDXV

Dynamic exercise intolerance

GSDV (MGP)

McArdle disease

GSDVII (PFK)

GSDIX (B kinase)

GSDXIII (beta enolase)

GSDIV (PGM1)

PGAM2

PGK

LDH

Average 20 year delay

between diagnosis and

patient first seeking a medical

opinion

Skeletal muscle energy metabolism

Greg Glassman 2003

-Creatine phosphate

8-10 seconds =100m

-Anaerobic glycolysis

30-90 seconds =200-400m

-Aerobic 800m-marathon

McArdle Disease

Autosomal Recessive

Prevalence

1100000 USA

1170000 Spain

1350000 Netherlands

Absence of MGP

Severely limited access to Glycogen stores

Inability to produce lactate during exercise

4

Haller RG Arch Neurol 2000 57923ndash924

Lucia A et alJ Neurol Neurosurg Psychiatr 2012

83322ndash328

van Alfen N et al Neuromuscul Disord 2002

12718ndash783

Godfrey Nature Neurol Rev 2016

Symptoms

Exercise intolerance (99)

Within 1-2 minutes of initiating aerobic activity

Immediate with isometric muscle activity

Canrsquot squat or run

Second wind (86)

Hyperuricaemia gout

Contracture

Acute rhabdomyolysis

Myoglobinuria (60)

Compartment syndrome

Acute renal failure (10)

Quinlivan JNNP 2010

Lucia JNNP 2012

Children

Difficulty crawling arms collapsing

Complain of leg pains as soon as they can walk want to

be carried everywhere

Unable to run more than a few metres get left behind by

other children in playground

Donrsquot understand second wind until 9-10 years (on

average)

Socially isolated and may have problems integrating in

school

May have some additional learning needs

6

Examination

Often normal

Muscle hypertrophy 40

Muscle wasting

Muscle weakness 20

shoulder girdle

axial paraspinal

7

Quinlivan et al JNNP 2010

Late onset axial wasting and weakness

Upper limb weakness scapular winging

Maximal exercise Isometric muscle contraction

bull Sprinting running

bull Lifting and carrying

bull Opening jars

bull Squattingcrouching

bull Muscle tension

Pain

Excitement

Fighting

Sex

bull Seizures

Brady et al BMJ 2014

All activities of daily

living are affected

Contracture and

compartment syndrome

Ocular involvement

Ptosis

Retinal detachment

Pattern Retinal dystrophy 10 patients all male and over 50yrs

Ophthalmology 11 Oct 2018

Mahroo OA Khan KN et al

12

Muscle glycogen metabolism disorders

Fixed muscle weakness

GSDII

Pompe Disease

GSDIII

GSDXV

Dynamic exercise intolerance

GSDV (MGP)

McArdle disease

GSDVII (PFK)

GSDIX (B kinase)

GSDXIII (beta enolase)

GSDIV (PGM1)

PGAM2

PGK

LDH

Average 20 year delay

between diagnosis and

patient first seeking a medical

opinion

Skeletal muscle energy metabolism

Greg Glassman 2003

-Creatine phosphate

8-10 seconds =100m

-Anaerobic glycolysis

30-90 seconds =200-400m

-Aerobic 800m-marathon

McArdle Disease

Autosomal Recessive

Prevalence

1100000 USA

1170000 Spain

1350000 Netherlands

Absence of MGP

Severely limited access to Glycogen stores

Inability to produce lactate during exercise

4

Haller RG Arch Neurol 2000 57923ndash924

Lucia A et alJ Neurol Neurosurg Psychiatr 2012

83322ndash328

van Alfen N et al Neuromuscul Disord 2002

12718ndash783

Godfrey Nature Neurol Rev 2016

Symptoms

Exercise intolerance (99)

Within 1-2 minutes of initiating aerobic activity

Immediate with isometric muscle activity

Canrsquot squat or run

Second wind (86)

Hyperuricaemia gout

Contracture

Acute rhabdomyolysis

Myoglobinuria (60)

Compartment syndrome

Acute renal failure (10)

Quinlivan JNNP 2010

Lucia JNNP 2012

Children

Difficulty crawling arms collapsing

Complain of leg pains as soon as they can walk want to

be carried everywhere

Unable to run more than a few metres get left behind by

other children in playground

Donrsquot understand second wind until 9-10 years (on

average)

Socially isolated and may have problems integrating in

school

May have some additional learning needs

6

Examination

Often normal

Muscle hypertrophy 40

Muscle wasting

Muscle weakness 20

shoulder girdle

axial paraspinal

7

Quinlivan et al JNNP 2010

Late onset axial wasting and weakness

Upper limb weakness scapular winging

Maximal exercise Isometric muscle contraction

bull Sprinting running

bull Lifting and carrying

bull Opening jars

bull Squattingcrouching

bull Muscle tension

Pain

Excitement

Fighting

Sex

bull Seizures

Brady et al BMJ 2014

All activities of daily

living are affected

Contracture and

compartment syndrome

Ocular involvement

Ptosis

Retinal detachment

Pattern Retinal dystrophy 10 patients all male and over 50yrs

Ophthalmology 11 Oct 2018

Mahroo OA Khan KN et al

12

Skeletal muscle energy metabolism

Greg Glassman 2003

-Creatine phosphate

8-10 seconds =100m

-Anaerobic glycolysis

30-90 seconds =200-400m

-Aerobic 800m-marathon

McArdle Disease

Autosomal Recessive

Prevalence

1100000 USA

1170000 Spain

1350000 Netherlands

Absence of MGP

Severely limited access to Glycogen stores

Inability to produce lactate during exercise

4

Haller RG Arch Neurol 2000 57923ndash924

Lucia A et alJ Neurol Neurosurg Psychiatr 2012

83322ndash328

van Alfen N et al Neuromuscul Disord 2002

12718ndash783

Godfrey Nature Neurol Rev 2016

Symptoms

Exercise intolerance (99)

Within 1-2 minutes of initiating aerobic activity

Immediate with isometric muscle activity

Canrsquot squat or run

Second wind (86)

Hyperuricaemia gout

Contracture

Acute rhabdomyolysis

Myoglobinuria (60)

Compartment syndrome

Acute renal failure (10)

Quinlivan JNNP 2010

Lucia JNNP 2012

Children

Difficulty crawling arms collapsing

Complain of leg pains as soon as they can walk want to

be carried everywhere

Unable to run more than a few metres get left behind by

other children in playground

Donrsquot understand second wind until 9-10 years (on

average)

Socially isolated and may have problems integrating in

school

May have some additional learning needs

6

Examination

Often normal

Muscle hypertrophy 40

Muscle wasting

Muscle weakness 20

shoulder girdle

axial paraspinal

7

Quinlivan et al JNNP 2010

Late onset axial wasting and weakness

Upper limb weakness scapular winging

Maximal exercise Isometric muscle contraction

bull Sprinting running

bull Lifting and carrying

bull Opening jars

bull Squattingcrouching

bull Muscle tension

Pain

Excitement

Fighting

Sex

bull Seizures

Brady et al BMJ 2014

All activities of daily

living are affected

Contracture and

compartment syndrome

Ocular involvement

Ptosis

Retinal detachment

Pattern Retinal dystrophy 10 patients all male and over 50yrs

Ophthalmology 11 Oct 2018

Mahroo OA Khan KN et al

12

McArdle Disease

Autosomal Recessive

Prevalence

1100000 USA

1170000 Spain

1350000 Netherlands

Absence of MGP

Severely limited access to Glycogen stores

Inability to produce lactate during exercise

4

Haller RG Arch Neurol 2000 57923ndash924

Lucia A et alJ Neurol Neurosurg Psychiatr 2012

83322ndash328

van Alfen N et al Neuromuscul Disord 2002

12718ndash783

Godfrey Nature Neurol Rev 2016

Symptoms

Exercise intolerance (99)

Within 1-2 minutes of initiating aerobic activity

Immediate with isometric muscle activity

Canrsquot squat or run

Second wind (86)

Hyperuricaemia gout

Contracture

Acute rhabdomyolysis

Myoglobinuria (60)

Compartment syndrome

Acute renal failure (10)

Quinlivan JNNP 2010

Lucia JNNP 2012

Children

Difficulty crawling arms collapsing

Complain of leg pains as soon as they can walk want to

be carried everywhere

Unable to run more than a few metres get left behind by

other children in playground

Donrsquot understand second wind until 9-10 years (on

average)

Socially isolated and may have problems integrating in

school

May have some additional learning needs

6

Examination

Often normal

Muscle hypertrophy 40

Muscle wasting

Muscle weakness 20

shoulder girdle

axial paraspinal

7

Quinlivan et al JNNP 2010

Late onset axial wasting and weakness

Upper limb weakness scapular winging

Maximal exercise Isometric muscle contraction

bull Sprinting running

bull Lifting and carrying

bull Opening jars

bull Squattingcrouching

bull Muscle tension

Pain

Excitement

Fighting

Sex

bull Seizures

Brady et al BMJ 2014

All activities of daily

living are affected

Contracture and

compartment syndrome

Ocular involvement

Ptosis

Retinal detachment

Pattern Retinal dystrophy 10 patients all male and over 50yrs

Ophthalmology 11 Oct 2018

Mahroo OA Khan KN et al

12

Symptoms

Exercise intolerance (99)

Within 1-2 minutes of initiating aerobic activity

Immediate with isometric muscle activity

Canrsquot squat or run

Second wind (86)

Hyperuricaemia gout

Contracture

Acute rhabdomyolysis

Myoglobinuria (60)

Compartment syndrome

Acute renal failure (10)

Quinlivan JNNP 2010

Lucia JNNP 2012

Children

Difficulty crawling arms collapsing

Complain of leg pains as soon as they can walk want to

be carried everywhere

Unable to run more than a few metres get left behind by

other children in playground

Donrsquot understand second wind until 9-10 years (on

average)

Socially isolated and may have problems integrating in

school

May have some additional learning needs

6

Examination

Often normal

Muscle hypertrophy 40

Muscle wasting

Muscle weakness 20

shoulder girdle

axial paraspinal

7

Quinlivan et al JNNP 2010

Late onset axial wasting and weakness

Upper limb weakness scapular winging

Maximal exercise Isometric muscle contraction

bull Sprinting running

bull Lifting and carrying

bull Opening jars

bull Squattingcrouching

bull Muscle tension

Pain

Excitement

Fighting

Sex

bull Seizures

Brady et al BMJ 2014

All activities of daily

living are affected

Contracture and

compartment syndrome

Ocular involvement

Ptosis

Retinal detachment

Pattern Retinal dystrophy 10 patients all male and over 50yrs

Ophthalmology 11 Oct 2018

Mahroo OA Khan KN et al

12

Children

Difficulty crawling arms collapsing

Complain of leg pains as soon as they can walk want to

be carried everywhere

Unable to run more than a few metres get left behind by

other children in playground

Donrsquot understand second wind until 9-10 years (on

average)

Socially isolated and may have problems integrating in

school

May have some additional learning needs

6

Examination

Often normal

Muscle hypertrophy 40

Muscle wasting

Muscle weakness 20

shoulder girdle

axial paraspinal

7

Quinlivan et al JNNP 2010

Late onset axial wasting and weakness

Upper limb weakness scapular winging

Maximal exercise Isometric muscle contraction

bull Sprinting running

bull Lifting and carrying

bull Opening jars

bull Squattingcrouching

bull Muscle tension

Pain

Excitement

Fighting

Sex

bull Seizures

Brady et al BMJ 2014

All activities of daily

living are affected

Contracture and

compartment syndrome

Ocular involvement

Ptosis

Retinal detachment

Pattern Retinal dystrophy 10 patients all male and over 50yrs

Ophthalmology 11 Oct 2018

Mahroo OA Khan KN et al

12

Examination

Often normal

Muscle hypertrophy 40

Muscle wasting

Muscle weakness 20

shoulder girdle

axial paraspinal

7

Quinlivan et al JNNP 2010

Late onset axial wasting and weakness

Upper limb weakness scapular winging

Maximal exercise Isometric muscle contraction

bull Sprinting running

bull Lifting and carrying

bull Opening jars

bull Squattingcrouching

bull Muscle tension

Pain

Excitement

Fighting

Sex

bull Seizures

Brady et al BMJ 2014

All activities of daily

living are affected

Contracture and

compartment syndrome

Ocular involvement

Ptosis

Retinal detachment

Pattern Retinal dystrophy 10 patients all male and over 50yrs

Ophthalmology 11 Oct 2018

Mahroo OA Khan KN et al

12

Late onset axial wasting and weakness

Upper limb weakness scapular winging

Maximal exercise Isometric muscle contraction

bull Sprinting running

bull Lifting and carrying

bull Opening jars

bull Squattingcrouching

bull Muscle tension

Pain

Excitement

Fighting

Sex

bull Seizures

Brady et al BMJ 2014

All activities of daily

living are affected

Contracture and

compartment syndrome

Ocular involvement

Ptosis

Retinal detachment

Pattern Retinal dystrophy 10 patients all male and over 50yrs

Ophthalmology 11 Oct 2018

Mahroo OA Khan KN et al

12

Upper limb weakness scapular winging

Maximal exercise Isometric muscle contraction

bull Sprinting running

bull Lifting and carrying

bull Opening jars

bull Squattingcrouching

bull Muscle tension

Pain

Excitement

Fighting

Sex

bull Seizures

Brady et al BMJ 2014

All activities of daily

living are affected

Contracture and

compartment syndrome

Ocular involvement

Ptosis

Retinal detachment

Pattern Retinal dystrophy 10 patients all male and over 50yrs

Ophthalmology 11 Oct 2018

Mahroo OA Khan KN et al

12

Maximal exercise Isometric muscle contraction

bull Sprinting running

bull Lifting and carrying

bull Opening jars

bull Squattingcrouching

bull Muscle tension

Pain

Excitement

Fighting

Sex

bull Seizures

Brady et al BMJ 2014

All activities of daily

living are affected

Contracture and

compartment syndrome

Ocular involvement

Ptosis

Retinal detachment

Pattern Retinal dystrophy 10 patients all male and over 50yrs

Ophthalmology 11 Oct 2018

Mahroo OA Khan KN et al

12

Contracture and

compartment syndrome

Ocular involvement

Ptosis

Retinal detachment

Pattern Retinal dystrophy 10 patients all male and over 50yrs

Ophthalmology 11 Oct 2018

Mahroo OA Khan KN et al

12

Ocular involvement

Ptosis

Retinal detachment

Pattern Retinal dystrophy 10 patients all male and over 50yrs

Ophthalmology 11 Oct 2018

Mahroo OA Khan KN et al

12

Atypical patients

Isolated progressive biceps weakness

Progressive proximal rimmed vacuolar myopathy

Moderate-severe axialshoulder weakness

LGMD phenotype

Late onset myopathy camptocormia and ptosis

Splice site mutation

mild phenotype 3 functioning enzyme

1Scarpelli M et al McArdle disease and sporadic inclusion body myositis Neuropath amp Applied

Neurobiol 35(4)442-5 2009)

2Witting N Duno M Piraud M Vissing J JAMA Neurology 71(1)88-90 2014)

Vissing J et al Brain 132(Pt 6)1545-52 2009)

3Cheraud et al Novel variant in the PYGM gene causing late-onset limb-girdle myopathy

ptosis and camptocormia Muscle Nerve 2017 e pub ahead of print

Co-morbidities in McArdle disease

N=118 McArdle

Disease

Adult male

population

Diabetes 8 67 48

Angina 10 85 48

MI 13 11 4

CVA 3 15 24

Gout 10 85 5

Sedentary lifestyle leading to chronic fatigue and chronic pain

Psychological issues

Obesity morbid obesity

High incidence of thyroid disease 11 hypothyroid

Thyroid medullary cancer 3 patients (prevalence 1-9100000)

Coronary artery disease

approx 100 asymptomatic patients screened

bull 18 asymptomatic coronary artery disease

bull 13 CAD requiring medical treatment

bull 5 required urgent intervention

bull 1x double bypass surgery

bull 3x stents

bull 1x Pacemaker

bull McArdle symptoms mask angina

Investigations Baseline Serum CK almost

always raised

16

Non-ischaemic forearm exercise test

17

Muscle Biopsy

Mc Ardle patient

Healthy individual

PYGM 11q12-132

20 exons

147 mutations

91 exonic 50 missense

18 deletions13 nonsense

11 splicing

19 (Nogales-Gadea et al Human mutation 2015 36 669ndash678)

[pR50 c148CgtT] Stop codon mutation in exon 1

Useful and inexpensive screening test

Nogales-Gadea 2015 Hum Mutat

Screening for R50X and G205S in UK patients prevents muscle biopsy

Minutes Heart Rate Walking

speed

kmhr

RPP

1 90 40 0

2 117 55 05

3 140 55 50

4 144 45 30

5 142 45 30

6 152 45 30

7 143 45 30

8 134 45 20

9 116 45 20

10 122 55 20

11 131 55 20

12 133 55 20

Borg RPP

Heart rate and perceived muscle pain responses to a functional walking test in McArdle disease Buckley JP Quinlivan RM Sim J Eston RG Short DS Journal of Sports Sciences 32(16)1561-9 2014

Co-morbidities in McArdle disease

N=118 McArdle

Disease

Adult male

population

Diabetes 8 67 48

Angina 10 85 48

MI 13 11 4

CVA 3 15 24

Gout 10 85 5

Sedentary lifestyle leading to chronic fatigue and chronic pain

Psychological issues

Obesity morbid obesity

High incidence of thyroid disease 11 hypothyroid

Thyroid medullary cancer 3 patients (prevalence 1-9100000)

Coronary artery disease

approx 100 asymptomatic patients screened

bull 18 asymptomatic coronary artery disease

bull 13 CAD requiring medical treatment

bull 5 required urgent intervention

bull 1x double bypass surgery

bull 3x stents

bull 1x Pacemaker

bull McArdle symptoms mask angina

Investigations Baseline Serum CK almost

always raised

16

Non-ischaemic forearm exercise test

17

Muscle Biopsy

Mc Ardle patient

Healthy individual

PYGM 11q12-132

20 exons

147 mutations

91 exonic 50 missense

18 deletions13 nonsense

11 splicing

19 (Nogales-Gadea et al Human mutation 2015 36 669ndash678)

[pR50 c148CgtT] Stop codon mutation in exon 1

Useful and inexpensive screening test

Nogales-Gadea 2015 Hum Mutat

Screening for R50X and G205S in UK patients prevents muscle biopsy

Minutes Heart Rate Walking

speed

kmhr

RPP

1 90 40 0

2 117 55 05

3 140 55 50

4 144 45 30

5 142 45 30

6 152 45 30

7 143 45 30

8 134 45 20

9 116 45 20

10 122 55 20

11 131 55 20

12 133 55 20

Borg RPP

Heart rate and perceived muscle pain responses to a functional walking test in McArdle disease Buckley JP Quinlivan RM Sim J Eston RG Short DS Journal of Sports Sciences 32(16)1561-9 2014

Coronary artery disease

approx 100 asymptomatic patients screened

bull 18 asymptomatic coronary artery disease

bull 13 CAD requiring medical treatment

bull 5 required urgent intervention

bull 1x double bypass surgery

bull 3x stents

bull 1x Pacemaker

bull McArdle symptoms mask angina

Investigations Baseline Serum CK almost

always raised

16

Non-ischaemic forearm exercise test

17

Muscle Biopsy

Mc Ardle patient

Healthy individual

PYGM 11q12-132

20 exons

147 mutations

91 exonic 50 missense

18 deletions13 nonsense

11 splicing

19 (Nogales-Gadea et al Human mutation 2015 36 669ndash678)

[pR50 c148CgtT] Stop codon mutation in exon 1

Useful and inexpensive screening test

Nogales-Gadea 2015 Hum Mutat

Screening for R50X and G205S in UK patients prevents muscle biopsy

Minutes Heart Rate Walking

speed

kmhr

RPP

1 90 40 0

2 117 55 05

3 140 55 50

4 144 45 30

5 142 45 30

6 152 45 30

7 143 45 30

8 134 45 20

9 116 45 20

10 122 55 20

11 131 55 20

12 133 55 20

Borg RPP

Heart rate and perceived muscle pain responses to a functional walking test in McArdle disease Buckley JP Quinlivan RM Sim J Eston RG Short DS Journal of Sports Sciences 32(16)1561-9 2014

Investigations Baseline Serum CK almost

always raised

16

Non-ischaemic forearm exercise test

17

Muscle Biopsy

Mc Ardle patient

Healthy individual

PYGM 11q12-132

20 exons

147 mutations

91 exonic 50 missense

18 deletions13 nonsense

11 splicing

19 (Nogales-Gadea et al Human mutation 2015 36 669ndash678)

[pR50 c148CgtT] Stop codon mutation in exon 1

Useful and inexpensive screening test

Nogales-Gadea 2015 Hum Mutat

Screening for R50X and G205S in UK patients prevents muscle biopsy

Minutes Heart Rate Walking

speed

kmhr

RPP

1 90 40 0

2 117 55 05

3 140 55 50

4 144 45 30

5 142 45 30

6 152 45 30

7 143 45 30

8 134 45 20

9 116 45 20

10 122 55 20

11 131 55 20

12 133 55 20

Borg RPP

Heart rate and perceived muscle pain responses to a functional walking test in McArdle disease Buckley JP Quinlivan RM Sim J Eston RG Short DS Journal of Sports Sciences 32(16)1561-9 2014

Non-ischaemic forearm exercise test

17

Muscle Biopsy

Mc Ardle patient

Healthy individual

PYGM 11q12-132

20 exons

147 mutations

91 exonic 50 missense

18 deletions13 nonsense

11 splicing

19 (Nogales-Gadea et al Human mutation 2015 36 669ndash678)

[pR50 c148CgtT] Stop codon mutation in exon 1

Useful and inexpensive screening test

Nogales-Gadea 2015 Hum Mutat

Screening for R50X and G205S in UK patients prevents muscle biopsy

Minutes Heart Rate Walking

speed

kmhr

RPP

1 90 40 0

2 117 55 05

3 140 55 50

4 144 45 30

5 142 45 30

6 152 45 30

7 143 45 30

8 134 45 20

9 116 45 20

10 122 55 20

11 131 55 20

12 133 55 20

Borg RPP

Heart rate and perceived muscle pain responses to a functional walking test in McArdle disease Buckley JP Quinlivan RM Sim J Eston RG Short DS Journal of Sports Sciences 32(16)1561-9 2014

Muscle Biopsy

Mc Ardle patient

Healthy individual

PYGM 11q12-132

20 exons

147 mutations

91 exonic 50 missense

18 deletions13 nonsense

11 splicing

19 (Nogales-Gadea et al Human mutation 2015 36 669ndash678)

[pR50 c148CgtT] Stop codon mutation in exon 1

Useful and inexpensive screening test

Nogales-Gadea 2015 Hum Mutat

Screening for R50X and G205S in UK patients prevents muscle biopsy

Minutes Heart Rate Walking

speed

kmhr

RPP

1 90 40 0

2 117 55 05

3 140 55 50

4 144 45 30

5 142 45 30

6 152 45 30

7 143 45 30

8 134 45 20

9 116 45 20

10 122 55 20

11 131 55 20

12 133 55 20

Borg RPP

Heart rate and perceived muscle pain responses to a functional walking test in McArdle disease Buckley JP Quinlivan RM Sim J Eston RG Short DS Journal of Sports Sciences 32(16)1561-9 2014

PYGM 11q12-132

20 exons

147 mutations

91 exonic 50 missense

18 deletions13 nonsense

11 splicing

19 (Nogales-Gadea et al Human mutation 2015 36 669ndash678)

[pR50 c148CgtT] Stop codon mutation in exon 1

Useful and inexpensive screening test

Nogales-Gadea 2015 Hum Mutat

Screening for R50X and G205S in UK patients prevents muscle biopsy

Minutes Heart Rate Walking

speed

kmhr

RPP

1 90 40 0

2 117 55 05

3 140 55 50

4 144 45 30

5 142 45 30

6 152 45 30

7 143 45 30

8 134 45 20

9 116 45 20

10 122 55 20

11 131 55 20

12 133 55 20

Borg RPP

Heart rate and perceived muscle pain responses to a functional walking test in McArdle disease Buckley JP Quinlivan RM Sim J Eston RG Short DS Journal of Sports Sciences 32(16)1561-9 2014

[pR50 c148CgtT] Stop codon mutation in exon 1

Useful and inexpensive screening test

Nogales-Gadea 2015 Hum Mutat

Screening for R50X and G205S in UK patients prevents muscle biopsy

Minutes Heart Rate Walking

speed

kmhr

RPP

1 90 40 0

2 117 55 05

3 140 55 50

4 144 45 30

5 142 45 30

6 152 45 30

7 143 45 30

8 134 45 20

9 116 45 20

10 122 55 20

11 131 55 20

12 133 55 20

Borg RPP

Heart rate and perceived muscle pain responses to a functional walking test in McArdle disease Buckley JP Quinlivan RM Sim J Eston RG Short DS Journal of Sports Sciences 32(16)1561-9 2014

Minutes Heart Rate Walking

speed

kmhr

RPP

1 90 40 0

2 117 55 05

3 140 55 50

4 144 45 30

5 142 45 30

6 152 45 30

7 143 45 30

8 134 45 20

9 116 45 20

10 122 55 20

11 131 55 20

12 133 55 20

Borg RPP

Heart rate and perceived muscle pain responses to a functional walking test in McArdle disease Buckley JP Quinlivan RM Sim J Eston RG Short DS Journal of Sports Sciences 32(16)1561-9 2014

Walking distance for n=75 patients tested 2014-

2015 (Richard Godfrey and Sherryl Chatfield)

Mean SF36v2 scores grouped by distance achieved on

12MWT at baseline (Jatin Pattni unpublished data)

Aerobic Training

Average increase in walking distance (from assessment to

follow-up) = 1173m

(39 follow-up patients)(Sherryl Chatfield)

SF 36 Change in Mental Component Score and

Physical Component Scores across 4 visits

(Jatin Pattni)

0

10

20

30

40

50

60

Visit 1 n 26 Visit 2 n 42 Visit 3 n 24 Visit 4 n 16

PCS MCS

Munguiacutea-Izquierdo D Santalla A Lucia A Cardiorespiratory fitness physical activity and quality of life in patients with McArdle disease Med Sci Sports Exerc 2015 Apr47(4)799-808

Mean SF36v2 scores grouped by distance achieved on

12MWT at baseline (Jatin Pattni unpublished data)

Aerobic Training

Average increase in walking distance (from assessment to

follow-up) = 1173m

(39 follow-up patients)(Sherryl Chatfield)

SF 36 Change in Mental Component Score and

Physical Component Scores across 4 visits

(Jatin Pattni)

0

10

20

30

40

50

60

Visit 1 n 26 Visit 2 n 42 Visit 3 n 24 Visit 4 n 16

PCS MCS

Munguiacutea-Izquierdo D Santalla A Lucia A Cardiorespiratory fitness physical activity and quality of life in patients with McArdle disease Med Sci Sports Exerc 2015 Apr47(4)799-808

Aerobic Training

Average increase in walking distance (from assessment to

follow-up) = 1173m

(39 follow-up patients)(Sherryl Chatfield)

SF 36 Change in Mental Component Score and

Physical Component Scores across 4 visits

(Jatin Pattni)

0

10

20

30

40

50

60

Visit 1 n 26 Visit 2 n 42 Visit 3 n 24 Visit 4 n 16

PCS MCS

Munguiacutea-Izquierdo D Santalla A Lucia A Cardiorespiratory fitness physical activity and quality of life in patients with McArdle disease Med Sci Sports Exerc 2015 Apr47(4)799-808

SF 36 Change in Mental Component Score and

Physical Component Scores across 4 visits

(Jatin Pattni)

0

10

20

30

40

50

60

Visit 1 n 26 Visit 2 n 42 Visit 3 n 24 Visit 4 n 16

PCS MCS

Munguiacutea-Izquierdo D Santalla A Lucia A Cardiorespiratory fitness physical activity and quality of life in patients with McArdle disease Med Sci Sports Exerc 2015 Apr47(4)799-808

Caution with isometric activity

Skeletal muscle energy metabolism

Greg Glassman 2003

-Creatine phosphate

8-10 seconds =100m

-Anaerobic glycolysis

30-90 seconds =200-400m

-Aerobic 800m-marathon

Resistance training in McArdle Disease

Aerobic warm up and

Glucose loading essential for

resistance training

Resistance (weight lifting) training in an adolescent with McArdle disease Garcia-Benitez S Fleck SJ Naclerio F Martin MA Lucia A Journal of Child Neurology 28(6)805-8 2013

Report on the EUROMAC McArdle Exercise Testing Workshop Madrid Spain 11-12 July 2014 Quinlivan R Lucia A Scalco RS Santalla A Pattni J Godfrey R Marti R Workshop Participants Neuromuscular Disorders 25(9)739-45 2015 Sep

Feasibility of resistance training in adult McArdle patients clinical outcomes and muscle strength and mass benefits Santalla A Munguia-Izquierdo D Brea-Alejo L Pagola-Aldazabal I Diez-Bermejo J Fleck SJ Ara I Lucia A Frontiers in aging neuroscience 6334 2014

Skeletal muscle energy metabolism

Greg Glassman 2003

-Creatine phosphate

8-10 seconds =100m

-Anaerobic glycolysis

30-90 seconds =200-400m

-Aerobic 800m-marathon

Resistance training in McArdle Disease

Aerobic warm up and

Glucose loading essential for

resistance training

Resistance (weight lifting) training in an adolescent with McArdle disease Garcia-Benitez S Fleck SJ Naclerio F Martin MA Lucia A Journal of Child Neurology 28(6)805-8 2013

Report on the EUROMAC McArdle Exercise Testing Workshop Madrid Spain 11-12 July 2014 Quinlivan R Lucia A Scalco RS Santalla A Pattni J Godfrey R Marti R Workshop Participants Neuromuscular Disorders 25(9)739-45 2015 Sep

Feasibility of resistance training in adult McArdle patients clinical outcomes and muscle strength and mass benefits Santalla A Munguia-Izquierdo D Brea-Alejo L Pagola-Aldazabal I Diez-Bermejo J Fleck SJ Ara I Lucia A Frontiers in aging neuroscience 6334 2014

Resistance training in McArdle Disease

Aerobic warm up and

Glucose loading essential for

resistance training

Resistance (weight lifting) training in an adolescent with McArdle disease Garcia-Benitez S Fleck SJ Naclerio F Martin MA Lucia A Journal of Child Neurology 28(6)805-8 2013

Report on the EUROMAC McArdle Exercise Testing Workshop Madrid Spain 11-12 July 2014 Quinlivan R Lucia A Scalco RS Santalla A Pattni J Godfrey R Marti R Workshop Participants Neuromuscular Disorders 25(9)739-45 2015 Sep

Feasibility of resistance training in adult McArdle patients clinical outcomes and muscle strength and mass benefits Santalla A Munguia-Izquierdo D Brea-Alejo L Pagola-Aldazabal I Diez-Bermejo J Fleck SJ Ara I Lucia A Frontiers in aging neuroscience 6334 2014

Phosphofructokinase deficiency

GSDVII (PFKM)

Severe exercise intolerance (nausea and

vomiting)

lsquoOut of wind phenomenonrsquo

Exercise is easier when fasted

Improved with aerobic exercise

Haemolytic anaemia

Gout

Cardiac involvement

Polyglucosan bodies seen on muscle biopsy

Sex CK 12 MWT

Myoglobinuria Age of onset

other

F 492 840 no child LV trabecular thickening Post partum haemorrhage Vomits with exercise

M 408 110 no child Haem anaemia LVH vomits with exercise

F 98 -unable no child SLE crohns Depression Hypertrophic LV

F 108 900 no child Vomits with exercise

F 891 -unable yes child Haem anaemia Mitral Valve replacement

M 480 446 yes child Gout haemolytic anaemia Vomits with exercise

PFKM mutations no genotype phenotype

correlation

Patient Allelle 1 Allele 2

1 Ashkenazi c450+1GgtA c2216del pPro738fs

2 Ashkenazi c450+1GgtA

c450+1GgtA

3 UK Caucasian pVal407 pVal407

4 Ashkenazi c450+1GgtA

c450+1GgtA

5 Pakistani c1340+5GgtA c1340+5GgtA

6 UK Caucasian c1087CgtT c1087CgtT

32

Management

Prevention of rhabdomyolysis

Gout preventiontreatment

Diet nutrition

Avoid glucose pre-exercise

Low carb

Fasting

Ketogenic diet

Strategies for exercise

bull Encourage aerobic exercise

Greg Glassman 2003

Enzyme Gene Inheritance Other features

Phosphorylase B kinase IX

PHKG1 AR

IX PHKA1 AR Exercise intol myoglobinuria

IX PHKA2 XL Liver and muscle disease

IX PHKB XL Liver and muscle disease

Phosphoglucomutase PGM1 AR Glycosylation disorder Abnormal transferrin glycoforms

Beta enolase 3

ENO3 AR Ex intolerance

Phosphoglycerate mutase PGAM2 AR Ex intol myoglobinuria Tubular aggregates

Phosphoglycerate kinase PGK XL Ex intol myoglobinuria Haemolytic anaemia Learning difficulty

Lactate dehydrogenase

LDHA AR Exercise intolerance myoglobinuria Skin rash

NGS panel

ACADVL AGL ALDOA CAV3 CPT1B CPT2 ENO3

ETFA EFTB ETFDH FBP2 GAA GBE1 GYG1

HADHA HADHB ISCU LDHA LPIN1 PFKM PGAM2

PGK1 PGM1 PYGM RBCK1 SLC22A5 PHKA1 RYR1

Cost pound1000

Result available in 4 months

Benefits large number of genes tested

Disadvantages false positive results not

all genes causing rhabdomyolysis

covered

Recurrent Rhabdomyolysis

28 year old male

Parents 1st cousins

Exercise induced pain and cramps since

childhood

Unable to sprint

Myalgia walking up hills

From 17 years recurrent episodes of

myoglobinuria

Maximum CK 75000 iul

Examination

bull Normal apart from mild

left sided scapular winging

bull 12 MWT 1000m

onset of pain at 12 mins

bull Decrease in lactate

from 22mmoll pre-exercise

to 10mmoll post exercise

MRI

Fatty infiltration soleus

Muscle biopsy

Acid phosphatase glycogen

Phosphorylase PFK B kinase

PGAM2 and RCE all normal

Dystrophin and sarcolemmal

Proteins normal

EM mild increase in Glycogen

Skin fibroblasts

normal FAOD

Genes sequenced

RYR1 LPIN1 PYGM PGM1 PFKM

Investigations

Resting CK 129mmoll

Carnitine acylcarnitines

normal

OA normal

CoQ10 normal

EMG NCS normal

Ischaemic forearm

exercise test

Time (minutes) 0 1 2 4 6 8 10

Lactate (mmolL 05-165) 142 279 294 298 216 206 187

Pyruvate (mmolL 45-150) 126 195 193 210 172 174 176

Ammonia (micromolL 11-32) 18 89 107 99 50 44 17

Lactatepyruvate ratio (10-20) 1127 1431 1523 1419 1256 1184 1063

Diagnosis GSDXIII

Homozygous mutations in Beta ENO3

p(Glu187Lys) c559GgtA

Skeletal muscle beta enolase concentration

007nmolminmg prot

Nr 066+- 01

(Ralph Wigley GOSH)

2nd

patient recently diagnosed

Highly Specialised Service for Mc Ardle

Disease and Related Disorders

Diagnosis and

management clinic

NHNN GOSH

Dr Quinlivan

Sherryl Chatfield

Dr Richard Godfrey

Dr Jatin Pattni

Clinical Fellow

Clinical Nurse

Specialist

Diagnosis

DNA testing

Dr Richard Kirk

Sheffield

Dr Carol Hardy

Birmingham

Muscle

biochemistry

(GOSH)

Professor Simon

Heales

Dr Ralph Wigley

40

Summary

Disorders of muscle glycogenolysis and glycolysis

present with exercise intolerance

Multi-system disorders

Symptoms occur within minutes of activity

Second wind occurs with GSDV

Out of wind occurs with GSDVII

Avoid carbs

Management includes preventing acute rhabdomyolysis

Progressive muscle atrophy and weakness

Ocular and cardiac involvement

Exercise is not harmful and is beneficial

41

Acknowledgements

NHNN ION

bull Sherryl Chatfield

bull Jatin Pattni

bull Andrew Wakelin

bull Suzanne Booth

bull Richard Godfrey

bull Charlotte Ellerton

bull Rachael Curruthers

bull Renata Scalco

bull Janice Holton

Sheffield Childrenrsquos Hospital

bull Richard Kirk

Birmingham Childrenrsquos Hospital

bull Mary Anne Preece

Great Ormond Street Hospital

bull Ralph Wigley

bull Simon Heales

Ramon Marti Toni Andreu Tomas Pinos

Xavier Ortager Alejandro Lucia Antonio

Toscano John Vissing Miguel Angel

MartinPascal Laforet Andrea Martinuzzi

Matthius Vorgerd Ron Haller Piraya Oflazer

Sabrina Sacconi

Sex CK 12 MWT

Myoglobinuria Age of onset

other

F 492 840 no child LV trabecular thickening Post partum haemorrhage Vomits with exercise

M 408 110 no child Haem anaemia LVH vomits with exercise

F 98 -unable no child SLE crohns Depression Hypertrophic LV

F 108 900 no child Vomits with exercise

F 891 -unable yes child Haem anaemia Mitral Valve replacement

M 480 446 yes child Gout haemolytic anaemia Vomits with exercise

PFKM mutations no genotype phenotype

correlation

Patient Allelle 1 Allele 2

1 Ashkenazi c450+1GgtA c2216del pPro738fs

2 Ashkenazi c450+1GgtA

c450+1GgtA

3 UK Caucasian pVal407 pVal407

4 Ashkenazi c450+1GgtA

c450+1GgtA

5 Pakistani c1340+5GgtA c1340+5GgtA

6 UK Caucasian c1087CgtT c1087CgtT

32

Management

Prevention of rhabdomyolysis

Gout preventiontreatment

Diet nutrition

Avoid glucose pre-exercise

Low carb

Fasting

Ketogenic diet

Strategies for exercise

bull Encourage aerobic exercise

Greg Glassman 2003

Enzyme Gene Inheritance Other features

Phosphorylase B kinase IX

PHKG1 AR

IX PHKA1 AR Exercise intol myoglobinuria

IX PHKA2 XL Liver and muscle disease

IX PHKB XL Liver and muscle disease

Phosphoglucomutase PGM1 AR Glycosylation disorder Abnormal transferrin glycoforms

Beta enolase 3

ENO3 AR Ex intolerance

Phosphoglycerate mutase PGAM2 AR Ex intol myoglobinuria Tubular aggregates

Phosphoglycerate kinase PGK XL Ex intol myoglobinuria Haemolytic anaemia Learning difficulty

Lactate dehydrogenase

LDHA AR Exercise intolerance myoglobinuria Skin rash

NGS panel

ACADVL AGL ALDOA CAV3 CPT1B CPT2 ENO3

ETFA EFTB ETFDH FBP2 GAA GBE1 GYG1

HADHA HADHB ISCU LDHA LPIN1 PFKM PGAM2

PGK1 PGM1 PYGM RBCK1 SLC22A5 PHKA1 RYR1

Cost pound1000

Result available in 4 months

Benefits large number of genes tested

Disadvantages false positive results not

all genes causing rhabdomyolysis

covered

Recurrent Rhabdomyolysis

28 year old male

Parents 1st cousins

Exercise induced pain and cramps since

childhood

Unable to sprint

Myalgia walking up hills

From 17 years recurrent episodes of

myoglobinuria

Maximum CK 75000 iul

Examination

bull Normal apart from mild

left sided scapular winging

bull 12 MWT 1000m

onset of pain at 12 mins

bull Decrease in lactate

from 22mmoll pre-exercise

to 10mmoll post exercise

MRI

Fatty infiltration soleus

Muscle biopsy

Acid phosphatase glycogen

Phosphorylase PFK B kinase

PGAM2 and RCE all normal

Dystrophin and sarcolemmal

Proteins normal

EM mild increase in Glycogen

Skin fibroblasts

normal FAOD

Genes sequenced

RYR1 LPIN1 PYGM PGM1 PFKM

Investigations

Resting CK 129mmoll

Carnitine acylcarnitines

normal

OA normal

CoQ10 normal

EMG NCS normal

Ischaemic forearm

exercise test

Time (minutes) 0 1 2 4 6 8 10

Lactate (mmolL 05-165) 142 279 294 298 216 206 187

Pyruvate (mmolL 45-150) 126 195 193 210 172 174 176

Ammonia (micromolL 11-32) 18 89 107 99 50 44 17

Lactatepyruvate ratio (10-20) 1127 1431 1523 1419 1256 1184 1063

Diagnosis GSDXIII

Homozygous mutations in Beta ENO3

p(Glu187Lys) c559GgtA

Skeletal muscle beta enolase concentration

007nmolminmg prot

Nr 066+- 01

(Ralph Wigley GOSH)

2nd

patient recently diagnosed

Highly Specialised Service for Mc Ardle

Disease and Related Disorders

Diagnosis and

management clinic

NHNN GOSH

Dr Quinlivan

Sherryl Chatfield

Dr Richard Godfrey

Dr Jatin Pattni

Clinical Fellow

Clinical Nurse

Specialist

Diagnosis

DNA testing

Dr Richard Kirk

Sheffield

Dr Carol Hardy

Birmingham

Muscle

biochemistry

(GOSH)

Professor Simon

Heales

Dr Ralph Wigley

40

Summary

Disorders of muscle glycogenolysis and glycolysis

present with exercise intolerance

Multi-system disorders

Symptoms occur within minutes of activity

Second wind occurs with GSDV

Out of wind occurs with GSDVII

Avoid carbs

Management includes preventing acute rhabdomyolysis

Progressive muscle atrophy and weakness

Ocular and cardiac involvement

Exercise is not harmful and is beneficial

41

Acknowledgements

NHNN ION

bull Sherryl Chatfield

bull Jatin Pattni

bull Andrew Wakelin

bull Suzanne Booth

bull Richard Godfrey

bull Charlotte Ellerton

bull Rachael Curruthers

bull Renata Scalco

bull Janice Holton

Sheffield Childrenrsquos Hospital

bull Richard Kirk

Birmingham Childrenrsquos Hospital

bull Mary Anne Preece

Great Ormond Street Hospital

bull Ralph Wigley

bull Simon Heales

Ramon Marti Toni Andreu Tomas Pinos

Xavier Ortager Alejandro Lucia Antonio

Toscano John Vissing Miguel Angel

MartinPascal Laforet Andrea Martinuzzi

Matthius Vorgerd Ron Haller Piraya Oflazer

Sabrina Sacconi

PFKM mutations no genotype phenotype

correlation

Patient Allelle 1 Allele 2

1 Ashkenazi c450+1GgtA c2216del pPro738fs

2 Ashkenazi c450+1GgtA

c450+1GgtA

3 UK Caucasian pVal407 pVal407

4 Ashkenazi c450+1GgtA

c450+1GgtA

5 Pakistani c1340+5GgtA c1340+5GgtA

6 UK Caucasian c1087CgtT c1087CgtT

32

Management

Prevention of rhabdomyolysis

Gout preventiontreatment

Diet nutrition

Avoid glucose pre-exercise

Low carb

Fasting

Ketogenic diet

Strategies for exercise

bull Encourage aerobic exercise

Greg Glassman 2003

Enzyme Gene Inheritance Other features

Phosphorylase B kinase IX

PHKG1 AR

IX PHKA1 AR Exercise intol myoglobinuria

IX PHKA2 XL Liver and muscle disease

IX PHKB XL Liver and muscle disease

Phosphoglucomutase PGM1 AR Glycosylation disorder Abnormal transferrin glycoforms

Beta enolase 3

ENO3 AR Ex intolerance

Phosphoglycerate mutase PGAM2 AR Ex intol myoglobinuria Tubular aggregates

Phosphoglycerate kinase PGK XL Ex intol myoglobinuria Haemolytic anaemia Learning difficulty

Lactate dehydrogenase

LDHA AR Exercise intolerance myoglobinuria Skin rash

NGS panel

ACADVL AGL ALDOA CAV3 CPT1B CPT2 ENO3

ETFA EFTB ETFDH FBP2 GAA GBE1 GYG1

HADHA HADHB ISCU LDHA LPIN1 PFKM PGAM2

PGK1 PGM1 PYGM RBCK1 SLC22A5 PHKA1 RYR1

Cost pound1000

Result available in 4 months

Benefits large number of genes tested

Disadvantages false positive results not

all genes causing rhabdomyolysis

covered

Recurrent Rhabdomyolysis

28 year old male

Parents 1st cousins

Exercise induced pain and cramps since

childhood

Unable to sprint

Myalgia walking up hills

From 17 years recurrent episodes of

myoglobinuria

Maximum CK 75000 iul

Examination

bull Normal apart from mild

left sided scapular winging

bull 12 MWT 1000m

onset of pain at 12 mins

bull Decrease in lactate

from 22mmoll pre-exercise

to 10mmoll post exercise

MRI

Fatty infiltration soleus

Muscle biopsy

Acid phosphatase glycogen

Phosphorylase PFK B kinase

PGAM2 and RCE all normal

Dystrophin and sarcolemmal

Proteins normal

EM mild increase in Glycogen

Skin fibroblasts

normal FAOD

Genes sequenced

RYR1 LPIN1 PYGM PGM1 PFKM

Investigations

Resting CK 129mmoll

Carnitine acylcarnitines

normal

OA normal

CoQ10 normal

EMG NCS normal

Ischaemic forearm

exercise test

Time (minutes) 0 1 2 4 6 8 10

Lactate (mmolL 05-165) 142 279 294 298 216 206 187

Pyruvate (mmolL 45-150) 126 195 193 210 172 174 176

Ammonia (micromolL 11-32) 18 89 107 99 50 44 17

Lactatepyruvate ratio (10-20) 1127 1431 1523 1419 1256 1184 1063

Diagnosis GSDXIII

Homozygous mutations in Beta ENO3

p(Glu187Lys) c559GgtA

Skeletal muscle beta enolase concentration

007nmolminmg prot

Nr 066+- 01

(Ralph Wigley GOSH)

2nd

patient recently diagnosed

Highly Specialised Service for Mc Ardle

Disease and Related Disorders

Diagnosis and

management clinic

NHNN GOSH

Dr Quinlivan

Sherryl Chatfield

Dr Richard Godfrey

Dr Jatin Pattni

Clinical Fellow

Clinical Nurse

Specialist

Diagnosis

DNA testing

Dr Richard Kirk

Sheffield

Dr Carol Hardy

Birmingham

Muscle

biochemistry

(GOSH)

Professor Simon

Heales

Dr Ralph Wigley

40

Summary

Disorders of muscle glycogenolysis and glycolysis

present with exercise intolerance

Multi-system disorders

Symptoms occur within minutes of activity

Second wind occurs with GSDV

Out of wind occurs with GSDVII

Avoid carbs

Management includes preventing acute rhabdomyolysis

Progressive muscle atrophy and weakness

Ocular and cardiac involvement

Exercise is not harmful and is beneficial

41

Acknowledgements

NHNN ION

bull Sherryl Chatfield

bull Jatin Pattni

bull Andrew Wakelin

bull Suzanne Booth

bull Richard Godfrey

bull Charlotte Ellerton

bull Rachael Curruthers

bull Renata Scalco

bull Janice Holton

Sheffield Childrenrsquos Hospital

bull Richard Kirk

Birmingham Childrenrsquos Hospital

bull Mary Anne Preece

Great Ormond Street Hospital

bull Ralph Wigley

bull Simon Heales

Ramon Marti Toni Andreu Tomas Pinos

Xavier Ortager Alejandro Lucia Antonio

Toscano John Vissing Miguel Angel

MartinPascal Laforet Andrea Martinuzzi

Matthius Vorgerd Ron Haller Piraya Oflazer

Sabrina Sacconi

32

Management

Prevention of rhabdomyolysis

Gout preventiontreatment

Diet nutrition

Avoid glucose pre-exercise

Low carb

Fasting

Ketogenic diet

Strategies for exercise

bull Encourage aerobic exercise

Greg Glassman 2003

Enzyme Gene Inheritance Other features

Phosphorylase B kinase IX

PHKG1 AR

IX PHKA1 AR Exercise intol myoglobinuria

IX PHKA2 XL Liver and muscle disease

IX PHKB XL Liver and muscle disease

Phosphoglucomutase PGM1 AR Glycosylation disorder Abnormal transferrin glycoforms

Beta enolase 3

ENO3 AR Ex intolerance

Phosphoglycerate mutase PGAM2 AR Ex intol myoglobinuria Tubular aggregates

Phosphoglycerate kinase PGK XL Ex intol myoglobinuria Haemolytic anaemia Learning difficulty

Lactate dehydrogenase

LDHA AR Exercise intolerance myoglobinuria Skin rash

NGS panel

ACADVL AGL ALDOA CAV3 CPT1B CPT2 ENO3

ETFA EFTB ETFDH FBP2 GAA GBE1 GYG1

HADHA HADHB ISCU LDHA LPIN1 PFKM PGAM2

PGK1 PGM1 PYGM RBCK1 SLC22A5 PHKA1 RYR1

Cost pound1000

Result available in 4 months

Benefits large number of genes tested

Disadvantages false positive results not

all genes causing rhabdomyolysis

covered

Recurrent Rhabdomyolysis

28 year old male

Parents 1st cousins

Exercise induced pain and cramps since

childhood

Unable to sprint

Myalgia walking up hills

From 17 years recurrent episodes of

myoglobinuria

Maximum CK 75000 iul

Examination

bull Normal apart from mild

left sided scapular winging

bull 12 MWT 1000m

onset of pain at 12 mins

bull Decrease in lactate

from 22mmoll pre-exercise

to 10mmoll post exercise

MRI

Fatty infiltration soleus

Muscle biopsy

Acid phosphatase glycogen

Phosphorylase PFK B kinase

PGAM2 and RCE all normal

Dystrophin and sarcolemmal

Proteins normal

EM mild increase in Glycogen

Skin fibroblasts

normal FAOD

Genes sequenced

RYR1 LPIN1 PYGM PGM1 PFKM

Investigations

Resting CK 129mmoll

Carnitine acylcarnitines

normal

OA normal

CoQ10 normal

EMG NCS normal

Ischaemic forearm

exercise test

Time (minutes) 0 1 2 4 6 8 10

Lactate (mmolL 05-165) 142 279 294 298 216 206 187

Pyruvate (mmolL 45-150) 126 195 193 210 172 174 176

Ammonia (micromolL 11-32) 18 89 107 99 50 44 17

Lactatepyruvate ratio (10-20) 1127 1431 1523 1419 1256 1184 1063

Diagnosis GSDXIII

Homozygous mutations in Beta ENO3

p(Glu187Lys) c559GgtA

Skeletal muscle beta enolase concentration

007nmolminmg prot

Nr 066+- 01

(Ralph Wigley GOSH)

2nd

patient recently diagnosed

Highly Specialised Service for Mc Ardle

Disease and Related Disorders

Diagnosis and

management clinic

NHNN GOSH

Dr Quinlivan

Sherryl Chatfield

Dr Richard Godfrey

Dr Jatin Pattni

Clinical Fellow

Clinical Nurse

Specialist

Diagnosis

DNA testing

Dr Richard Kirk

Sheffield

Dr Carol Hardy

Birmingham

Muscle

biochemistry

(GOSH)

Professor Simon

Heales

Dr Ralph Wigley

40

Summary

Disorders of muscle glycogenolysis and glycolysis

present with exercise intolerance

Multi-system disorders

Symptoms occur within minutes of activity

Second wind occurs with GSDV

Out of wind occurs with GSDVII

Avoid carbs

Management includes preventing acute rhabdomyolysis

Progressive muscle atrophy and weakness

Ocular and cardiac involvement

Exercise is not harmful and is beneficial

41

Acknowledgements

NHNN ION

bull Sherryl Chatfield

bull Jatin Pattni

bull Andrew Wakelin

bull Suzanne Booth

bull Richard Godfrey

bull Charlotte Ellerton

bull Rachael Curruthers

bull Renata Scalco

bull Janice Holton

Sheffield Childrenrsquos Hospital

bull Richard Kirk

Birmingham Childrenrsquos Hospital

bull Mary Anne Preece

Great Ormond Street Hospital

bull Ralph Wigley

bull Simon Heales

Ramon Marti Toni Andreu Tomas Pinos

Xavier Ortager Alejandro Lucia Antonio

Toscano John Vissing Miguel Angel

MartinPascal Laforet Andrea Martinuzzi

Matthius Vorgerd Ron Haller Piraya Oflazer

Sabrina Sacconi

Enzyme Gene Inheritance Other features

Phosphorylase B kinase IX

PHKG1 AR

IX PHKA1 AR Exercise intol myoglobinuria

IX PHKA2 XL Liver and muscle disease

IX PHKB XL Liver and muscle disease

Phosphoglucomutase PGM1 AR Glycosylation disorder Abnormal transferrin glycoforms

Beta enolase 3

ENO3 AR Ex intolerance

Phosphoglycerate mutase PGAM2 AR Ex intol myoglobinuria Tubular aggregates

Phosphoglycerate kinase PGK XL Ex intol myoglobinuria Haemolytic anaemia Learning difficulty

Lactate dehydrogenase

LDHA AR Exercise intolerance myoglobinuria Skin rash

NGS panel

ACADVL AGL ALDOA CAV3 CPT1B CPT2 ENO3

ETFA EFTB ETFDH FBP2 GAA GBE1 GYG1

HADHA HADHB ISCU LDHA LPIN1 PFKM PGAM2

PGK1 PGM1 PYGM RBCK1 SLC22A5 PHKA1 RYR1

Cost pound1000

Result available in 4 months

Benefits large number of genes tested

Disadvantages false positive results not

all genes causing rhabdomyolysis

covered

Recurrent Rhabdomyolysis

28 year old male

Parents 1st cousins

Exercise induced pain and cramps since

childhood

Unable to sprint

Myalgia walking up hills

From 17 years recurrent episodes of

myoglobinuria

Maximum CK 75000 iul

Examination

bull Normal apart from mild

left sided scapular winging

bull 12 MWT 1000m

onset of pain at 12 mins

bull Decrease in lactate

from 22mmoll pre-exercise

to 10mmoll post exercise

MRI

Fatty infiltration soleus

Muscle biopsy

Acid phosphatase glycogen

Phosphorylase PFK B kinase

PGAM2 and RCE all normal

Dystrophin and sarcolemmal

Proteins normal

EM mild increase in Glycogen

Skin fibroblasts

normal FAOD

Genes sequenced

RYR1 LPIN1 PYGM PGM1 PFKM

Investigations

Resting CK 129mmoll

Carnitine acylcarnitines

normal

OA normal

CoQ10 normal

EMG NCS normal

Ischaemic forearm

exercise test

Time (minutes) 0 1 2 4 6 8 10

Lactate (mmolL 05-165) 142 279 294 298 216 206 187

Pyruvate (mmolL 45-150) 126 195 193 210 172 174 176

Ammonia (micromolL 11-32) 18 89 107 99 50 44 17

Lactatepyruvate ratio (10-20) 1127 1431 1523 1419 1256 1184 1063

Diagnosis GSDXIII

Homozygous mutations in Beta ENO3

p(Glu187Lys) c559GgtA

Skeletal muscle beta enolase concentration

007nmolminmg prot

Nr 066+- 01

(Ralph Wigley GOSH)

2nd

patient recently diagnosed

Highly Specialised Service for Mc Ardle

Disease and Related Disorders

Diagnosis and

management clinic

NHNN GOSH

Dr Quinlivan

Sherryl Chatfield

Dr Richard Godfrey

Dr Jatin Pattni

Clinical Fellow

Clinical Nurse

Specialist

Diagnosis

DNA testing

Dr Richard Kirk

Sheffield

Dr Carol Hardy

Birmingham

Muscle

biochemistry

(GOSH)

Professor Simon

Heales

Dr Ralph Wigley

40

Summary

Disorders of muscle glycogenolysis and glycolysis

present with exercise intolerance

Multi-system disorders

Symptoms occur within minutes of activity

Second wind occurs with GSDV

Out of wind occurs with GSDVII

Avoid carbs

Management includes preventing acute rhabdomyolysis

Progressive muscle atrophy and weakness

Ocular and cardiac involvement

Exercise is not harmful and is beneficial

41

Acknowledgements

NHNN ION

bull Sherryl Chatfield

bull Jatin Pattni

bull Andrew Wakelin

bull Suzanne Booth

bull Richard Godfrey

bull Charlotte Ellerton

bull Rachael Curruthers

bull Renata Scalco

bull Janice Holton

Sheffield Childrenrsquos Hospital

bull Richard Kirk

Birmingham Childrenrsquos Hospital

bull Mary Anne Preece

Great Ormond Street Hospital

bull Ralph Wigley

bull Simon Heales

Ramon Marti Toni Andreu Tomas Pinos

Xavier Ortager Alejandro Lucia Antonio

Toscano John Vissing Miguel Angel

MartinPascal Laforet Andrea Martinuzzi

Matthius Vorgerd Ron Haller Piraya Oflazer

Sabrina Sacconi

NGS panel

ACADVL AGL ALDOA CAV3 CPT1B CPT2 ENO3

ETFA EFTB ETFDH FBP2 GAA GBE1 GYG1

HADHA HADHB ISCU LDHA LPIN1 PFKM PGAM2

PGK1 PGM1 PYGM RBCK1 SLC22A5 PHKA1 RYR1

Cost pound1000

Result available in 4 months

Benefits large number of genes tested

Disadvantages false positive results not

all genes causing rhabdomyolysis

covered

Recurrent Rhabdomyolysis

28 year old male

Parents 1st cousins

Exercise induced pain and cramps since

childhood

Unable to sprint

Myalgia walking up hills

From 17 years recurrent episodes of

myoglobinuria

Maximum CK 75000 iul

Examination

bull Normal apart from mild

left sided scapular winging

bull 12 MWT 1000m

onset of pain at 12 mins

bull Decrease in lactate

from 22mmoll pre-exercise

to 10mmoll post exercise

MRI

Fatty infiltration soleus

Muscle biopsy

Acid phosphatase glycogen

Phosphorylase PFK B kinase

PGAM2 and RCE all normal

Dystrophin and sarcolemmal

Proteins normal

EM mild increase in Glycogen

Skin fibroblasts

normal FAOD

Genes sequenced

RYR1 LPIN1 PYGM PGM1 PFKM

Investigations

Resting CK 129mmoll

Carnitine acylcarnitines

normal

OA normal

CoQ10 normal

EMG NCS normal

Ischaemic forearm

exercise test

Time (minutes) 0 1 2 4 6 8 10

Lactate (mmolL 05-165) 142 279 294 298 216 206 187

Pyruvate (mmolL 45-150) 126 195 193 210 172 174 176

Ammonia (micromolL 11-32) 18 89 107 99 50 44 17

Lactatepyruvate ratio (10-20) 1127 1431 1523 1419 1256 1184 1063

Diagnosis GSDXIII

Homozygous mutations in Beta ENO3

p(Glu187Lys) c559GgtA

Skeletal muscle beta enolase concentration

007nmolminmg prot

Nr 066+- 01

(Ralph Wigley GOSH)

2nd

patient recently diagnosed

Highly Specialised Service for Mc Ardle

Disease and Related Disorders

Diagnosis and

management clinic

NHNN GOSH

Dr Quinlivan

Sherryl Chatfield

Dr Richard Godfrey

Dr Jatin Pattni

Clinical Fellow

Clinical Nurse

Specialist

Diagnosis

DNA testing

Dr Richard Kirk

Sheffield

Dr Carol Hardy

Birmingham

Muscle

biochemistry

(GOSH)

Professor Simon

Heales

Dr Ralph Wigley

40

Summary

Disorders of muscle glycogenolysis and glycolysis

present with exercise intolerance

Multi-system disorders

Symptoms occur within minutes of activity

Second wind occurs with GSDV

Out of wind occurs with GSDVII

Avoid carbs

Management includes preventing acute rhabdomyolysis

Progressive muscle atrophy and weakness

Ocular and cardiac involvement

Exercise is not harmful and is beneficial

41

Acknowledgements

NHNN ION

bull Sherryl Chatfield

bull Jatin Pattni

bull Andrew Wakelin

bull Suzanne Booth

bull Richard Godfrey

bull Charlotte Ellerton

bull Rachael Curruthers

bull Renata Scalco

bull Janice Holton

Sheffield Childrenrsquos Hospital

bull Richard Kirk

Birmingham Childrenrsquos Hospital

bull Mary Anne Preece

Great Ormond Street Hospital

bull Ralph Wigley

bull Simon Heales

Ramon Marti Toni Andreu Tomas Pinos

Xavier Ortager Alejandro Lucia Antonio

Toscano John Vissing Miguel Angel

MartinPascal Laforet Andrea Martinuzzi

Matthius Vorgerd Ron Haller Piraya Oflazer

Sabrina Sacconi

Recurrent Rhabdomyolysis

28 year old male

Parents 1st cousins

Exercise induced pain and cramps since

childhood

Unable to sprint

Myalgia walking up hills

From 17 years recurrent episodes of

myoglobinuria

Maximum CK 75000 iul

Examination

bull Normal apart from mild

left sided scapular winging

bull 12 MWT 1000m

onset of pain at 12 mins

bull Decrease in lactate

from 22mmoll pre-exercise

to 10mmoll post exercise

MRI

Fatty infiltration soleus

Muscle biopsy

Acid phosphatase glycogen

Phosphorylase PFK B kinase

PGAM2 and RCE all normal

Dystrophin and sarcolemmal

Proteins normal

EM mild increase in Glycogen

Skin fibroblasts

normal FAOD

Genes sequenced

RYR1 LPIN1 PYGM PGM1 PFKM

Investigations

Resting CK 129mmoll

Carnitine acylcarnitines

normal

OA normal

CoQ10 normal

EMG NCS normal

Ischaemic forearm

exercise test

Time (minutes) 0 1 2 4 6 8 10

Lactate (mmolL 05-165) 142 279 294 298 216 206 187

Pyruvate (mmolL 45-150) 126 195 193 210 172 174 176

Ammonia (micromolL 11-32) 18 89 107 99 50 44 17

Lactatepyruvate ratio (10-20) 1127 1431 1523 1419 1256 1184 1063

Diagnosis GSDXIII

Homozygous mutations in Beta ENO3

p(Glu187Lys) c559GgtA

Skeletal muscle beta enolase concentration

007nmolminmg prot

Nr 066+- 01

(Ralph Wigley GOSH)

2nd

patient recently diagnosed

Highly Specialised Service for Mc Ardle

Disease and Related Disorders

Diagnosis and

management clinic

NHNN GOSH

Dr Quinlivan

Sherryl Chatfield

Dr Richard Godfrey

Dr Jatin Pattni

Clinical Fellow

Clinical Nurse

Specialist

Diagnosis

DNA testing

Dr Richard Kirk

Sheffield

Dr Carol Hardy

Birmingham

Muscle

biochemistry

(GOSH)

Professor Simon

Heales

Dr Ralph Wigley

40

Summary

Disorders of muscle glycogenolysis and glycolysis

present with exercise intolerance

Multi-system disorders

Symptoms occur within minutes of activity

Second wind occurs with GSDV

Out of wind occurs with GSDVII

Avoid carbs

Management includes preventing acute rhabdomyolysis

Progressive muscle atrophy and weakness

Ocular and cardiac involvement

Exercise is not harmful and is beneficial

41

Acknowledgements

NHNN ION

bull Sherryl Chatfield

bull Jatin Pattni

bull Andrew Wakelin

bull Suzanne Booth

bull Richard Godfrey

bull Charlotte Ellerton

bull Rachael Curruthers

bull Renata Scalco

bull Janice Holton

Sheffield Childrenrsquos Hospital

bull Richard Kirk

Birmingham Childrenrsquos Hospital

bull Mary Anne Preece

Great Ormond Street Hospital

bull Ralph Wigley

bull Simon Heales

Ramon Marti Toni Andreu Tomas Pinos

Xavier Ortager Alejandro Lucia Antonio

Toscano John Vissing Miguel Angel

MartinPascal Laforet Andrea Martinuzzi

Matthius Vorgerd Ron Haller Piraya Oflazer

Sabrina Sacconi

Examination

bull Normal apart from mild

left sided scapular winging

bull 12 MWT 1000m

onset of pain at 12 mins

bull Decrease in lactate

from 22mmoll pre-exercise

to 10mmoll post exercise

MRI

Fatty infiltration soleus

Muscle biopsy

Acid phosphatase glycogen

Phosphorylase PFK B kinase

PGAM2 and RCE all normal

Dystrophin and sarcolemmal

Proteins normal

EM mild increase in Glycogen

Skin fibroblasts

normal FAOD

Genes sequenced

RYR1 LPIN1 PYGM PGM1 PFKM

Investigations

Resting CK 129mmoll

Carnitine acylcarnitines

normal

OA normal

CoQ10 normal

EMG NCS normal

Ischaemic forearm

exercise test

Time (minutes) 0 1 2 4 6 8 10

Lactate (mmolL 05-165) 142 279 294 298 216 206 187

Pyruvate (mmolL 45-150) 126 195 193 210 172 174 176

Ammonia (micromolL 11-32) 18 89 107 99 50 44 17

Lactatepyruvate ratio (10-20) 1127 1431 1523 1419 1256 1184 1063

Diagnosis GSDXIII

Homozygous mutations in Beta ENO3

p(Glu187Lys) c559GgtA

Skeletal muscle beta enolase concentration

007nmolminmg prot

Nr 066+- 01

(Ralph Wigley GOSH)

2nd

patient recently diagnosed

Highly Specialised Service for Mc Ardle

Disease and Related Disorders

Diagnosis and

management clinic

NHNN GOSH

Dr Quinlivan

Sherryl Chatfield

Dr Richard Godfrey

Dr Jatin Pattni

Clinical Fellow

Clinical Nurse

Specialist

Diagnosis

DNA testing

Dr Richard Kirk

Sheffield

Dr Carol Hardy

Birmingham

Muscle

biochemistry

(GOSH)

Professor Simon

Heales

Dr Ralph Wigley

40

Summary

Disorders of muscle glycogenolysis and glycolysis

present with exercise intolerance

Multi-system disorders

Symptoms occur within minutes of activity

Second wind occurs with GSDV

Out of wind occurs with GSDVII

Avoid carbs

Management includes preventing acute rhabdomyolysis

Progressive muscle atrophy and weakness

Ocular and cardiac involvement

Exercise is not harmful and is beneficial

41

Acknowledgements

NHNN ION

bull Sherryl Chatfield

bull Jatin Pattni

bull Andrew Wakelin

bull Suzanne Booth

bull Richard Godfrey

bull Charlotte Ellerton

bull Rachael Curruthers

bull Renata Scalco

bull Janice Holton

Sheffield Childrenrsquos Hospital

bull Richard Kirk

Birmingham Childrenrsquos Hospital

bull Mary Anne Preece

Great Ormond Street Hospital

bull Ralph Wigley

bull Simon Heales

Ramon Marti Toni Andreu Tomas Pinos

Xavier Ortager Alejandro Lucia Antonio

Toscano John Vissing Miguel Angel

MartinPascal Laforet Andrea Martinuzzi

Matthius Vorgerd Ron Haller Piraya Oflazer

Sabrina Sacconi

MRI

Fatty infiltration soleus

Muscle biopsy

Acid phosphatase glycogen

Phosphorylase PFK B kinase

PGAM2 and RCE all normal

Dystrophin and sarcolemmal

Proteins normal

EM mild increase in Glycogen

Skin fibroblasts

normal FAOD

Genes sequenced

RYR1 LPIN1 PYGM PGM1 PFKM

Investigations

Resting CK 129mmoll

Carnitine acylcarnitines

normal

OA normal

CoQ10 normal

EMG NCS normal

Ischaemic forearm

exercise test

Time (minutes) 0 1 2 4 6 8 10

Lactate (mmolL 05-165) 142 279 294 298 216 206 187

Pyruvate (mmolL 45-150) 126 195 193 210 172 174 176

Ammonia (micromolL 11-32) 18 89 107 99 50 44 17

Lactatepyruvate ratio (10-20) 1127 1431 1523 1419 1256 1184 1063

Diagnosis GSDXIII

Homozygous mutations in Beta ENO3

p(Glu187Lys) c559GgtA

Skeletal muscle beta enolase concentration

007nmolminmg prot

Nr 066+- 01

(Ralph Wigley GOSH)

2nd

patient recently diagnosed

Highly Specialised Service for Mc Ardle

Disease and Related Disorders

Diagnosis and

management clinic

NHNN GOSH

Dr Quinlivan

Sherryl Chatfield

Dr Richard Godfrey

Dr Jatin Pattni

Clinical Fellow

Clinical Nurse

Specialist

Diagnosis

DNA testing

Dr Richard Kirk

Sheffield

Dr Carol Hardy

Birmingham

Muscle

biochemistry

(GOSH)

Professor Simon

Heales

Dr Ralph Wigley

40

Summary

Disorders of muscle glycogenolysis and glycolysis

present with exercise intolerance

Multi-system disorders

Symptoms occur within minutes of activity

Second wind occurs with GSDV

Out of wind occurs with GSDVII

Avoid carbs

Management includes preventing acute rhabdomyolysis

Progressive muscle atrophy and weakness

Ocular and cardiac involvement

Exercise is not harmful and is beneficial

41

Acknowledgements

NHNN ION

bull Sherryl Chatfield

bull Jatin Pattni

bull Andrew Wakelin

bull Suzanne Booth

bull Richard Godfrey

bull Charlotte Ellerton

bull Rachael Curruthers

bull Renata Scalco

bull Janice Holton

Sheffield Childrenrsquos Hospital

bull Richard Kirk

Birmingham Childrenrsquos Hospital

bull Mary Anne Preece

Great Ormond Street Hospital

bull Ralph Wigley

bull Simon Heales

Ramon Marti Toni Andreu Tomas Pinos

Xavier Ortager Alejandro Lucia Antonio

Toscano John Vissing Miguel Angel

MartinPascal Laforet Andrea Martinuzzi

Matthius Vorgerd Ron Haller Piraya Oflazer

Sabrina Sacconi

Investigations

Resting CK 129mmoll

Carnitine acylcarnitines

normal

OA normal

CoQ10 normal

EMG NCS normal

Ischaemic forearm

exercise test

Time (minutes) 0 1 2 4 6 8 10

Lactate (mmolL 05-165) 142 279 294 298 216 206 187

Pyruvate (mmolL 45-150) 126 195 193 210 172 174 176

Ammonia (micromolL 11-32) 18 89 107 99 50 44 17

Lactatepyruvate ratio (10-20) 1127 1431 1523 1419 1256 1184 1063

Diagnosis GSDXIII

Homozygous mutations in Beta ENO3

p(Glu187Lys) c559GgtA

Skeletal muscle beta enolase concentration

007nmolminmg prot

Nr 066+- 01

(Ralph Wigley GOSH)

2nd

patient recently diagnosed

Highly Specialised Service for Mc Ardle

Disease and Related Disorders

Diagnosis and

management clinic

NHNN GOSH

Dr Quinlivan

Sherryl Chatfield

Dr Richard Godfrey

Dr Jatin Pattni

Clinical Fellow

Clinical Nurse

Specialist

Diagnosis

DNA testing

Dr Richard Kirk

Sheffield

Dr Carol Hardy

Birmingham

Muscle

biochemistry

(GOSH)

Professor Simon

Heales

Dr Ralph Wigley

40

Summary

Disorders of muscle glycogenolysis and glycolysis

present with exercise intolerance

Multi-system disorders

Symptoms occur within minutes of activity

Second wind occurs with GSDV

Out of wind occurs with GSDVII

Avoid carbs

Management includes preventing acute rhabdomyolysis

Progressive muscle atrophy and weakness

Ocular and cardiac involvement

Exercise is not harmful and is beneficial

41

Acknowledgements

NHNN ION

bull Sherryl Chatfield

bull Jatin Pattni

bull Andrew Wakelin

bull Suzanne Booth

bull Richard Godfrey

bull Charlotte Ellerton

bull Rachael Curruthers

bull Renata Scalco

bull Janice Holton

Sheffield Childrenrsquos Hospital

bull Richard Kirk

Birmingham Childrenrsquos Hospital

bull Mary Anne Preece

Great Ormond Street Hospital

bull Ralph Wigley

bull Simon Heales

Ramon Marti Toni Andreu Tomas Pinos

Xavier Ortager Alejandro Lucia Antonio

Toscano John Vissing Miguel Angel

MartinPascal Laforet Andrea Martinuzzi

Matthius Vorgerd Ron Haller Piraya Oflazer

Sabrina Sacconi

Diagnosis GSDXIII

Homozygous mutations in Beta ENO3

p(Glu187Lys) c559GgtA

Skeletal muscle beta enolase concentration

007nmolminmg prot

Nr 066+- 01

(Ralph Wigley GOSH)

2nd

patient recently diagnosed

Highly Specialised Service for Mc Ardle

Disease and Related Disorders

Diagnosis and

management clinic

NHNN GOSH

Dr Quinlivan

Sherryl Chatfield

Dr Richard Godfrey

Dr Jatin Pattni

Clinical Fellow

Clinical Nurse

Specialist

Diagnosis

DNA testing

Dr Richard Kirk

Sheffield

Dr Carol Hardy

Birmingham

Muscle

biochemistry

(GOSH)

Professor Simon

Heales

Dr Ralph Wigley

40

Summary

Disorders of muscle glycogenolysis and glycolysis

present with exercise intolerance

Multi-system disorders

Symptoms occur within minutes of activity

Second wind occurs with GSDV

Out of wind occurs with GSDVII

Avoid carbs

Management includes preventing acute rhabdomyolysis

Progressive muscle atrophy and weakness

Ocular and cardiac involvement

Exercise is not harmful and is beneficial

41

Acknowledgements

NHNN ION

bull Sherryl Chatfield

bull Jatin Pattni

bull Andrew Wakelin

bull Suzanne Booth

bull Richard Godfrey

bull Charlotte Ellerton

bull Rachael Curruthers

bull Renata Scalco

bull Janice Holton

Sheffield Childrenrsquos Hospital

bull Richard Kirk

Birmingham Childrenrsquos Hospital

bull Mary Anne Preece

Great Ormond Street Hospital

bull Ralph Wigley

bull Simon Heales

Ramon Marti Toni Andreu Tomas Pinos

Xavier Ortager Alejandro Lucia Antonio

Toscano John Vissing Miguel Angel

MartinPascal Laforet Andrea Martinuzzi

Matthius Vorgerd Ron Haller Piraya Oflazer

Sabrina Sacconi

Highly Specialised Service for Mc Ardle

Disease and Related Disorders

Diagnosis and

management clinic

NHNN GOSH

Dr Quinlivan

Sherryl Chatfield

Dr Richard Godfrey

Dr Jatin Pattni

Clinical Fellow

Clinical Nurse

Specialist

Diagnosis

DNA testing

Dr Richard Kirk

Sheffield

Dr Carol Hardy

Birmingham

Muscle

biochemistry

(GOSH)

Professor Simon

Heales

Dr Ralph Wigley

40

Summary

Disorders of muscle glycogenolysis and glycolysis

present with exercise intolerance

Multi-system disorders

Symptoms occur within minutes of activity

Second wind occurs with GSDV

Out of wind occurs with GSDVII

Avoid carbs

Management includes preventing acute rhabdomyolysis

Progressive muscle atrophy and weakness

Ocular and cardiac involvement

Exercise is not harmful and is beneficial

41

Acknowledgements

NHNN ION

bull Sherryl Chatfield

bull Jatin Pattni

bull Andrew Wakelin

bull Suzanne Booth

bull Richard Godfrey

bull Charlotte Ellerton

bull Rachael Curruthers

bull Renata Scalco

bull Janice Holton

Sheffield Childrenrsquos Hospital

bull Richard Kirk

Birmingham Childrenrsquos Hospital

bull Mary Anne Preece

Great Ormond Street Hospital

bull Ralph Wigley

bull Simon Heales

Ramon Marti Toni Andreu Tomas Pinos

Xavier Ortager Alejandro Lucia Antonio

Toscano John Vissing Miguel Angel

MartinPascal Laforet Andrea Martinuzzi

Matthius Vorgerd Ron Haller Piraya Oflazer

Sabrina Sacconi

Summary

Disorders of muscle glycogenolysis and glycolysis

present with exercise intolerance

Multi-system disorders

Symptoms occur within minutes of activity

Second wind occurs with GSDV

Out of wind occurs with GSDVII

Avoid carbs

Management includes preventing acute rhabdomyolysis

Progressive muscle atrophy and weakness

Ocular and cardiac involvement

Exercise is not harmful and is beneficial

41

Acknowledgements

NHNN ION

bull Sherryl Chatfield

bull Jatin Pattni

bull Andrew Wakelin

bull Suzanne Booth

bull Richard Godfrey

bull Charlotte Ellerton

bull Rachael Curruthers

bull Renata Scalco

bull Janice Holton

Sheffield Childrenrsquos Hospital

bull Richard Kirk

Birmingham Childrenrsquos Hospital

bull Mary Anne Preece

Great Ormond Street Hospital

bull Ralph Wigley

bull Simon Heales

Ramon Marti Toni Andreu Tomas Pinos

Xavier Ortager Alejandro Lucia Antonio

Toscano John Vissing Miguel Angel

MartinPascal Laforet Andrea Martinuzzi

Matthius Vorgerd Ron Haller Piraya Oflazer

Sabrina Sacconi

Acknowledgements

NHNN ION

bull Sherryl Chatfield

bull Jatin Pattni

bull Andrew Wakelin

bull Suzanne Booth

bull Richard Godfrey

bull Charlotte Ellerton

bull Rachael Curruthers

bull Renata Scalco

bull Janice Holton

Sheffield Childrenrsquos Hospital

bull Richard Kirk

Birmingham Childrenrsquos Hospital

bull Mary Anne Preece

Great Ormond Street Hospital

bull Ralph Wigley

bull Simon Heales

Ramon Marti Toni Andreu Tomas Pinos

Xavier Ortager Alejandro Lucia Antonio

Toscano John Vissing Miguel Angel

MartinPascal Laforet Andrea Martinuzzi

Matthius Vorgerd Ron Haller Piraya Oflazer

Sabrina Sacconi