SSIEM 2016

IN PILLOLE

Mitocondrio

Pearson syndromesideroblastic anemia exocrine pancreas dysfunction (steatorrhea)usually fatal in infancy

Kearns-Sayre syndrome (KSS) obligatory triad:1)Onset before age 20 years2)Pigmentary retinopathy FOO atypical "salt and pepper" retinopathy; ERG often reveals retinal dystrophy3) Progressive external ophthalmoplegia (PEO)

At least one of the following must also be present:Cardiac conduction blockCerebrospinal fluid protein concentration greater than 100 mg/dLCerebellar ataxia

PEOPtosisophthalmoplegia oropharyngeal weakness, variably severe proximal limb weakness

Mitochondrial DNA Deletion Syndromes

Oa 9 pz

5 KSS

NORMALE O POCO SIGNIFICATIVO

4 PMS

3 IDROSSIBUTIRRATO

2 METIL – 3 OH BUTIRRATO

NB AO NORMALI NON ESCLUDE MUTAZIONI MT

DNA

20 pz

Mut. in 12 (60%)

67/113

NB

Detection rate circa 60%

POLIMICROGIRIA?

10 pz con MD

CISTI CEREBELLARI?

2 m

Drug resistent EE

Develop Delay

Seconday microc.

MPS of Infancy

↓ I – IV complex

Difetti nella biosintesi di CQ?

80 pz

Dai 4 mesi

-Ipotono

-Ritardo motorio

-Deterioramento in corso di infezioni intercorrenti

-Acrocianosi / Petecchie

-Diarrea emorragica

-Dismorfismi

-Acidosi lattica + ↑ C4 e C5

-Aciduria Etilmalonica

MNGIE: deoxyribonucleosideEE: sulfide

↑S2H

↓SCAD e COX

sulfite

FARS2

..in addition, double immunostaining with the antibodies against FARS2 and COX IV, a mitochondria marker, revealed that FARS2 was colocalized with COX IV..

6 m motor delay

9 m motor regression

15 m myoclonic seizures

Subsequent spastic paraplegia

Aminoacyl-tRNA synthetases (aaRSs) form a set of housekeeping enzymes that play a crucial role in cellular translation. aaRSs chemically ligate tRNAs with their cognate amino acids producing the aminoacyl-tRNAs (aa-tRNAs) that subsequently bind to the elongation factor, facilitating delivery to the ribosome for mRNA decoding

FARS2 (6p25.1)encodes mitochondrial phenylalanyltRNAsynthetase, which catalyzes the attachment of phenylalanine to itscognate mitochondrial tRNA,

Ma

creatina

1) 17 yrs

- 6 m: develop.delay + Feb seizures > DR epilepsy

- 21 m: gen. dystonic movements

2) 11 yrs (1 cusin)

- 13 m dystonic limb movements

Increased GAA - 80 pts Mental retardation + behavioural disturnbance (Autism,ADHD)

Expressive speech delayHypotonia in young children and later ataxia and dystonia (chorea and episodic ataxia aneddoctal)

Seizures (absence, tonic clonic, myoclonic, focal, generalized but expecially head drop seizures, myoclonic, mycolconic astatic, spasms)

EEG aspecific or high amplitude theta/delta, several cases with multifocal spikesBasal ganglia changes in globus pallidum

TP

Nuove malattie / Nuovi geni

7 GENI

AA

22q11.2 del syndrome

PRODH (prol. oxidase)

17 yrs

Previously

Psycomotor delay

OCD

Mild dysmorphic

NO seizures

And than

Schizophrenia

PRODH (22q11) mut

PROLINA da considerare in particolare se dist. psichiatrico è anticipato da RM e epilessia

ucd

ROUTINE in ASD?

AA plasma?

Ac orotico urina?

Ammonio AST ALT?

ASD

1) 12 AA

2) 15 AA

vit

1) 9m rit.psicomot. + corea + a. megal. (madre anemia pernic)

2) 23m diff. alim. + rit. Psicomot + tremore + (alim. esclusiva seno)

3) 9aa debolezza progress. + parestesia AA inf + pancitopenia + sedia a rotelle

4) 15aa anemia perniciosa + dol. addome+ vomito intermittente + astenia + vertigine

5) 18aa debolezza + diff. cammino + parestesie

DG (MMA e cbl)

malnutrizione severa

anemia perniciosa

abuso N2-O

HC transcobalamina 1

TCII transcobalamina 2