lysosomal disease.docx

8/16/2019 lysosomal disease.docx

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Table 4Print

Lysosomal Storage Disorders

Disease (OMIM

Number)

Defective Proteins

or Enzymes

Defective

Genes

(Chromoso

mal

Location)

Comments

Mucopolysaccharidosis (MPS)

MPS I-H (Hurler's

syndrome; 607014)

MPS I-S (Scheie's

syndrome; 607016)

MPS I H/S (Hurler-

Scheie syndrome;

60701)

!-l-Iduronid"se I#$%

(4&16)

Onset: In I-H* 1st yr

In I-S* + yr

In I-H/S* , yr

Urine

metabolites:#erm"t"n

sul."te*he&"rin

sul."te

linical !eatures:orne"l

cloudin* sti.. oints*

contr"ctures* dysostosis

multi&le2* co"rse ."cies*

co"rse h"ir*

m"crolossi"*

or"nome"ly*

intellectu"l dis"3ility ith

reression* 5"l5ul"r he"rt

dise"se* he"rin "nd

5ision im&"irment*

inuin"l "nd um3ilic"l

herni"* slee& "&ne"*

hydroce&h"lus

Treatment: Su&&orti5e

c"re* enyme

re&l"cement* stem cell or


2/30

3one m"rro

tr"ns&l"nt"tion

MPS II (Hunter's

syndrome; 000)

Iduron"te sul."te

sul."t"se

I#S (89:) Onset: :,4 yr

Urine

metabolites:#erm"t"n

sul."te*he&"rin

sul."te

linical !eatures:Simil"r

to Hurler's syndrome 3ut

milder "nd no corne"l

cloudin

In mild .orm* norm"l

intellience

In se5ere .orm*

&roressi5e intellectu"l

"nd &hysic"l dis"3ility*

de"th 3e.ore "e 1


c"re* stem cell or 3one

m"rro tr"ns&l"nt"tion

MPS III (S"n.ili&&o's

syndrome)

Onset: :,6 yr

Urine

metabolites:He&"rin

sul."te



ith se5ere intellectu"l

dis"3ility "nd mild

som"tic m"ni.est"tions

y&e III-% (::00) He&"r"n-S-sul."te

sul."mid"se

S


3/30

Treatment: Su&&orti5e c"re

y&e III-# (::40) N -"cetyl-

lucos"minine-6-

sul."te sul."t"se

S

(1:914)

MPS I@ (Mor9uio's

syndrome

Onset: 1,4 yr

Urine metabolites:Aer"tin

sul."te; in I@-=* "lso

chondroitin 6-sul."te



ith se5ere 3one

ch"nes includin

odontoid hy&o&l"si";

&ossi3ly norm"l

intellience


c"re

y&e I@-% (:000)


4/30

sul."te* chondroitin 4-* 6-

sul."te



re"ter 5"ri"tion in

se5erity




MPS I8

(hy"luronid"se

de.iciency; 6014:)

Hy"luronid"se

de.iciency

HE%?1

(&:1-

&:1:)

Onset: 6 mo

Urine metabolites:>one

linical !eatures:=il"ter"l

so.t-tissue &eri"rticul"r

m"sses* dysmor&hic

.e"tures* short st"ture*

norm"l intellience

Treatment: >ot

est"3lished

Mucolipidosis (ML)

M? I See Si"lidosis ty&e I

(3elo)

M? II (I-cell dise"se;

::00)

N -%cetyllucos"minyl-

1-

&hos&hotr"ns.eer"se

c"t"lytic su3unit

P%

(49:1-9:)

Onset: 1st yr

Urine metabolites: >o

muco&olys"cch"rides



more se5ere; &resence o.

&h"se-dense inclusion

3odies in .i3ro3l"sts (I-

cells)


c"re


5/30

M? III (&seudo-

Hurler's

&olydystro&hy)

>-"cetyllucos"minyl-

1-

&hos&hotr"ns.eer"se

Onset: :,4 yr



to M? II 3ut l"ter onset"nd &ossi3le sur5i5"l to

"dulthood


c"re

y&e III-% (::600) "t"lytic su3unit P%

(49:1-9:)

y&e III- (::60) Su3str"te-reconition

su3unit

P%<

(16&)

M? I@ See Si"loli&idosis

(3elo)

C C

Sphingolipidosis


6/30

dystoni"* loss o.

&sychomotor milestones*

mild 5iscerome"ly "nd

3one "3norm"lity


c"re

y&e III ("dult ty&e;

:060)

Type """ onset: ,0 yr


linical

!eatures: %nioFer"tom"

cor&oris di..usum*

s&ondyloe&i&hyse"ldys&l"si"* dys"rthri"*

cere3ell"r dys.unction; no

m"cul"r red s&ots or

5iscerome"ly


c"re

one

linical !eatures: #oll-liFe

."cies; cherry-red retin";

e"rly 3lindness;

e2"er"ted st"rtle

re.le2; initi"l hy&otoni"

.olloed 3y hy&ertoni";

&sychomotor ret"rd"tion

.olloed 3y reression*

seiures* "nd im&"ired

se"tin; de"th 3y "e

yr

In ty&e I* incre"sed

y&e I ("y-S"chs

dise"se; :7:00)

B-He2os"minid"se % HG8%

(19:-

9:4)

y&e II (S"ndho..'s

dise"se; :600)

B-He2os"minid"se = HG8=

(91)

y&e III (u5enile

ty&e)

B-He2os"minid"se % C


7/30

.re9uency in %shFen"i

es

iem"nn-PicF

dise"se (see "lso

>iem"nn-PicF

dise"se ty&es "nd

#* 3elo)

S&hinomyelin"se SMP#1

(11&14-

&11)

y&e % (:7:00) Onset: 6 mo

linical !eatures:P cells)*

de"th 3y "e yr




y&e = (607616) Onset: @"ri"3le


8/30

linical !eatures: Much

milder sym&toms* no

neuroloic in5ol5ement*

sur5i5"l to "dulthood

Incre"sed .re9uency in

%shFen"i es




one

linical

!eatures:He&"tos&lenom

e"ly* osteolytic lesions

ith 3one &"in* "5"scul"r

necrosis o. the .emor"l

he"d* 5erte3r"l

com&ression*throm3ocyto&eni"*

"nemi"

Incre"sed .re9uency in

%shFen"i es


c"re* s&lenectomy*

enyme re&l"cement*

3one m"rro or stem cell

tr"ns&l"nt"tion

y&e II (in."ntile .orm;

:000)

Onset: In."ncy


linical !eatures:In."ntile

hydro&s*


9/30

he&"tos&lenome"ly*

dys&h"i"* 3one lesions*

hy&ertonicity*

&seudo3ul3"r &"lsy*

l"ryne"l s&"sm*

ichthyosis*

de5elo&ment"l del"y*

hy&ers&lenism* de"th 3y

"e : yr


c"re

y&e III (u5enile

.orm* >orr3ottni"n

ty&e; :1000)

Onset: 4, yr



to ty&e II e2ce&t milder*

&ossi3le sur5i5"l into

"dulthood


c"re

J"r3er's dise"se(li&or"nulom"tosis;

::000)

er"mid"se %S%H (&::-&:1)

Onset: Jirst eeFs o. li.e

Urine

metabolites:er"mide

linical

!eatures:?i&or"nulom"t

osis* &eri"rticul"r

su3cut"neous nodules*

irrit"3ility* ho"rse cry*

&sychomotor "nd roth

del"y* res&ir"tory

insu..iciency* histiocytosis

in multi&le tissues*

ne&hro&"thy*

he&"tos&lenome"ly*

cherry-red m"cul"r s&ot


10/30

Milder 5"ri"nts sometimes

di5ided into 7 su3ty&es

"ccordin to se5erity


c"re

J"3ry's dise"se

(0100)

rihe2osylcer"mide !-

"l"ctosid"se


11/30

• ?"te in."ntile

.orm

• u5enile .orm

• %dult .orm

• Pseudode.icien

cy .orm

Jor "dult .orm* "ny "e

".ter &u3erty

Urine

metabolites:Sul."tides

linical !eatures: K&tic

"tro&hy* "ll 3l"dder

dys.unction* urin"ry

incontinence* hy&otoni"*

"it distur3"nce*

hy&ore.le2i" .olloed 3y

hy&erre.le2i"* 3ul3"r

&"lsies* "t"2i"* chore"*

demyelin"tion "ndde5elo&ment"l

reression* incre"sed

SJ &rotein

In "dult .orm* "lso

schio&hreni"-liFe

sym&toms

&seudode.iciency

ch"r"cteried 3y mild

decre"se in enyme

"cti5ity ithout neuroloic

deener"tion


c"re* consider"tion o.


tr"ns&l"nt"tion

Mucosul."tidosis

(multi&le sul."t"sede.iciency; :7::00)

Sul."t"se-modi.yin

."ctor-1

S$MJ1

(&:6)

Onset: In."ncy

Urine

metabolites:Sul."tides*

muco&olys"cch"rides


to l"te in."ntile .orm o.

met"chrom"tic


12/30

leuFodystro&hy* &lus

ichthyosis "nd dysostosis

multi&le2


c"re

Ar"33e's dise"se

(:4:00)

•

• In."ntile .orm

• ?"te in."ntile

.orm

• u5enile .orm

• %dult .orm

one

linical !eatures:


13/30

Urine

metabolites:Sul."tides

linical !eatures: In

s"&osin = de.iciency*

.e"tures simil"r to those

o. met"chrom"tic

leuFodystro&hy

In s"&osin de.iciency*

.e"tures simil"r to those

o. iem"nn-PicF

dise"se* ty&es %

"nd =* "3o5e)

Onset: Hihly 5"ri"3le

(e"rly or l"te in."ncy*

"dolescence* "dulthood)


linical !eatures:@ertic"l

"e &"lsy*

he&"tos&lenome"ly*

neon"t"l "undice*

dys&h"i"* hy&otoni"

.olloed 3y s&"sticity*

seiures* cere3ell"r

"t"2i"* dys"rthri"*

&sychomotor del"y "nd

y&e 1/y&e #

((:7::0)

>P1 &rotein >P1

(1911-91:)

y&e : (6076:) G&ididym"l secretory

&rotein 1 (HG1;

>P: &rotein)

>P:

(149:4)


14/30

deener"tion* &sychosis

"nd 3eh"5ior"l &ro3lem*

.et"l "scites* .o"m cells

"nd se"-3lue histiocytes

"s in >iem"nn-PicF

dise"se ty&es % "nd =?ysosom"l "cid li&"se

de.iciency (:7000)

•

• olm"n's

dise"se

• holesteryl

ester stor"edise"se(GS#)

?ysosom"l "cid li&"se ?IP% (109:4-

9:)

Onset: In olm"n's

dise"se* in."ncy

In GS#* 5"ri"3le


linical !eatures:


15/30

Treatment: Jor olm"n's

dise"se* no e..ecti5e

ther"&y

Jor GS#* st"tins &lus "

lo-cholesterol diet

hel&.ul

ere3rotendinous

2"nthom"tosis

(cholest"nol

li&idosis; :1700)

Sterol :7-hydro2yl"se EP:7%

(:9-9ter)

Onset: %dolescence

Urine

metabolites:Gle5"ted 7-

!-hydro2yl"ted 3ile

"lcohol

linical !eatures:u5enilec"t"r"cts* tendon "nd

sFin 2"nthom"s*

2"nthel"sm"* .r"ctures*

"therosclerosis*

dementi"* s&in"l cord

&"resis* cere3ell"r "t"2i"*

de5elo&ment"l dis"3ility*

&seudo3ul3"r &"r"lysis*

leuFodystro&hy*&eri&her"l neuro&"thy

Treatment:henodeo2ych

olic "cid* st"tins

>euron"l ceroid

li&o.uscinosis

Onset: In in."ntile .orm* 6,

1: mo

In l"te in."ntile .orm* :,4

yr

In u5enile .orms (includin

?>)* 4,10 yr

In "dult .orm* :0, yr

In 5"ri"nt in."ntile .orms*

4,7 yr

In."ntile .orm (?>1*

S"nt"5uori-H"lti"

dise"se; :670)

P"lmitoyl-&rotein

thioester"se-1

PP1 (1&:)

?"te in."ntile .orm

(?>:* "nsFy-

=ielschosFy

dise"se; :0400)

?ysosom"l &e&st"tin-

insensiti5e &e&tid"se

?>:

(11&1)


16/30

In &roressi5e e&ile&sy

.orm* ,10 yr


linical !eatures: In

in."ntile "nd l"te in."ntile

.orms* de5elo&ment"l

del"y* microce&h"ly* o&tic

"nd cere3r"l "tro&hy*

retin"l deener"tion*

3lindness* .le2ion

contr"ctures* hy&otoni"*

"t"2i"* myoclonus*

seiures* loss o. s&eech*

hy&ere2cit"3ility*

u5enile .orm (?>*

="tten dise"se*

@ot-S&ielmeyer

dise"se; :04:00)

?ysosom"l

tr"nsmem3r"ne

?> &rotein

?>

(16&1:1)

%dult .orm (?>4*

Au.s' dise"se;

:0400)

P"lmitoyl-&rotein

thioester"se-1

PP1 (1&:)

@"ri"nt l"te in."ntile

.orm* Jinnish ty&e

(?>; :671)

?ysosom"l

tr"nsmem3r"ne

?> &rotein

?>

(19:1-

9:)

@"ri"nt l"te in."ntile

.orm (?>6;

60170)

r"nsmem3r"ne ?>6

&rotein

?>6

(19:1-

9:)

Proressi5e e&ile&sy

ith intellectu"l

dis"3ility (60014)

r"nsmem3r"ne ?>

&rotein

?> (&ter-

&::)

?> (600) C C

Oligosaccharidosis and related disorders

Si"lidosis (:60) >eur"minid"se 1

(si"lid"se)

>G$1

(6&:1)y&e I (cherry-red

m"cul"r s&ot-

myoclonus

syndrome* mild

.orm)

Onset: ,: yr

Urine

metabolites:Incre"sed

si"lylolios"cch"rides

linical !eatures:herry-


17/30

red m"cul"r s&ot*

insidious 5ision loss*

c"t"r"cts* &roressi5e

myoclonus "nd "t"2i"*

norm"l intellience*

incre"sed dee& tendon

re.le2


c"re

y&e II (conenit"l*

in."ntile* u5enile*

"nd childhood

.orms)

Onset: In conenit"l .orm*

in utero

In in."ntile .orm* 3irth to 1:

mo

In u5enile "nd childhood

.orms* :,:0 yr

Urine


si"lylolios"cch"rides

linical !eatures: %ll o.

.e"tures o. ty&e I &lus

co"rse ."cies* hy&otoni"*

he&"tome"ly* "scites*

inuin"l herni"* roth

del"y* muscle "stin*

l"rynom"l"ci"*

dysostosis multi&le2


c"re


18/30

de.iciency; :640)

•

• >eon"t"l .orm

• ?"te in."ntile

.orm

• u5enile/"dult

.orm

ide 5"ri"3ility

Urine

metabolites:Gle5"ted

si"lylolios"cch"rides 3ut

no .ree si"lic "cid

linical !eatures:o"rse

."cies* corne"l cloudin*

cherry-red m"cul"r s&ot*

intellectu"l dis"3ility*

seiures* dysostosis

multi&le2* he"rin loss*

hem"niom"s* 5"l5ul"r

he"rt dise"se


c"re

Si"loli&idosis

(&hos&holi&idosis;

mucoli&idosis I@*

=erm"n dise"se;

::60)

MK?>1

(1&1-

&1:)

Onset: 1st yr

Urine metabolites: >o

muco&olys"cch"rides

linical !eatures:Se5ere

(=erm"n dise"se) "nd

mild .orms

#e5elo&ment"l del"y*

corne"l o&"cities* 5isu"l

de.iciency* str"3ismus*

hy&otoni"* incre"sed

dee& tendon re.le2es; no

r"dior"&hic sFelet"l

"3norm"lity*

m"croce&h"ly* or

or"nome"ly


c"re

M"nnosidosis Onset: In ty&e I* ,1: mo


19/30

In ty&e II* 1,4 yr

Urine

metabolites:M"nnose-

rich olios"cch"rides


."cies* m"croce&h"ly*

m"crolossi"* c"t"r"cts*

ini5"l hy&ertro&hy*

sliht

he&"tos&lenome"ly*

dysostosis multi&le2*

hy&otoni"* he"rin loss*

3oed .emur*&"ncyto&eni"* recurrent

res&ir"tory in.ections*

immunode.iciency "nd

"utoimmunity*

de5elo&ment"l dis"3ilities




tr"ns&l"nt"tion

!-M"nnosidosis

(:400)* ty&e I

(se5ere) or II (mild)

!-#-M"nnosid"se M%>:=1

(1cen-

91:)

B-M"nnosidosis

(:410)

B-#-M"nnosid"se M%>=%

(49::-9:)

Onset: 1,6 yr

Urine

metabolites:#is"cch"rid

es* m"nnosyl-(1-4)-N -

"cetyllucos"mine*he&"ri

n

sul."te


."cies* de".ness* del"yed

s&eech* hy&er"cti5ity*

enit"l "nioFer"tom"*


20/30

tortuous conuncti5"l

5essels




tr"ns&l"nt"tion

Jucosidosis (:0000)

•

• y&e I (se5ere

in."ntile .orm)

•

• y&e II (mild

.orm)

!-?-Jucosid"se J$%1

(1&4)

Onset: In ty&e I* ,1 mo

In ty&e II* 1,: yr

Urine

metabolites:Klios"cch"

rides

linical !eatures: Short

st"ture* roth del"y*

co"rse ."cies*

m"crolossi"*

c"rdiome"ly* recurrent

res&ir"tory in.ections*

dysostosis multi&le2*

herni"s*

he&"tos&lenome"ly*

"nioFer"tom"*

"nhidrosis "nd ele5"ted

se"t chloride*

de5elo&ment"l dis"3ility*

hy&otoni" ch"nin to

hy&ertoni"* cere3r"l

"tro&hy* seiures* s&"stic

9u"dri&lei"* 5"cuol"ted

lym&hocytes

Most &"tients .rom It"ly or

southestern $S




tr"ns&l"nt"tion


21/30

%s&"rtyllucos"minur

i" (:0400)

N -

%s&"rtyllucos"minid

"se

%


22/30

Fy&hoscoliosis* 5erte3r"l

com&ression* c"r&ot"rs"l

osteolysis* "nFylosis o.

sm"ll oints o. .eet*

di..use thicFened sFin*

hy&er&iment"tion*

hy&ertrichosis


c"re

Schindler's dise"se N -%cetyl-

"l"ctos"minid"se

!->%


23/30


."cies* de".ness*

conuncti5"l "nd retin"l

5"scul"r tortuosity*

"nioFer"tom" cor&oris

di..usum* tel"niect"si"*

lym&hedem"* mild

intellectu"l im&"irment*

&eri&her"l "2on"l

neuro&"thy


c"re

y&e III (intermedi"te

.orm; 60:41)

Onset: hildhood

Urine

metabolites:Klios"cch"

rides "nd K-linFed

si"lo&e&tides

linical

!eatures:Intermedi"te

3eteen ty&es I "nd II;

5"ri"3le "nd r"nin .romseiures "nd moder"te

&sychomotor ret"rd"tion

to mild "utistic .e"tures

ith s&eech "nd

l"nu"e del"y


c"re

onenit"l disorderso. N -lycosyl"tion*

ty&e I (&re-


24/30

neuroloic "nd

neuroloic-

multi5iscer"l .orms;

:1:06)

e-: (16&1-

&1:)

hih-"rched or cle.t &"l"te*

str"3ismus* retinitis

&imentos"* &eric"rdi"l

e..usion* c"rdiomyo&"thy*

he&"tome"ly* 5omitin*

di"rrhe"* li5er .i3rosis*

&rim"ry o5"ri"n ."ilure*

ren"l cysts* ne&hrosis*

&ro2im"l tu3ulo&"thy*

Fy&hosis* oint

contr"ctures* ecto&ic ."t

&"ds* or"ne-&eel sFin*

muscle e"Fness*

hy&otoni"* stroFeliFe

e&isodes* seiures*

oli5o&ontine hy&o&l"si"*

&eri&her"l neuro&"thy*

hy&othyroidism*

hy&erinsulinism* ."ctor 8I

de.iciency* "ntithrom3in III

de.iciency*

throm3ocytosis*

decre"sed I% "nd I


25/30

M"nnosyltr"ns.er"se (9::)

#< I (600) $#P-%cLdolichyl-

P >%c


26/30

In."ntile si"lic "cid

stor"e disorder

(:6:0)

>" &hos&h"te

cotr"ns&orter

S?17%

(6914-91)

Onset: %t 3irth

Urine


.ree si"lic "cid

linical !eatures:


27/30

e&imer"se/N -

"cetylm"nnos"mine

Fin"se

Urine


.ree si"lic "cid


."cies ith norm"l

roth* de5elo&ment"l

del"y* slee& "&ne"*

hy&o&l"stic ni&&les*

he&"tos&lenome"ly*

inuin"l herni"s*

ener"lied hirsutism*

seiures

Treatment: Su&&orti5ec"re

>euron"l ceroid

li&o.uscinosis

(?>* ?>*

?>6* ?>)

See Kther li&idoses*

"3o5e

ystinosis ystinosin (lysosom"l

cystine tr"ns&orter)

>S

(17&1)

In."ntile ne&hro&"thic

.orm (:100)

Onset: 1st yr

Urine metabolites:Den"l

J"nconi syndrome

linical !eatures:


28/30

myo&"thy* dys&h"i"*

cere3r"l "tro&hy* norm"l

intellience 3ut

neuroloic deterior"tion

in lon-term sur5i5ors

ystine "ccumul"tion

throuhout

reticuloendotheli"l

system* =* "nd

corne"

Treatment:De&l"cement

ther"&y .or J"nconi

syndrome* ren"ltr"ns&l"nt .or ."ilure*

cyste"mine or"lly or "s

eyedro&s* roth

hormone

?"te-onset u5enile

.orm (:100)

Onset: 1:,1 yr


J"nconi syndrome


to in."ntile .orm 3ut

milder

Treatment: Simil"r to th"t

.or in."ntile .orm

%dult non-

ne&hro&"thic .orm

(:170)

Onset: G"rly teens to

"dulthood


J"nconi syndrome


to in."ntile .orm 3ut no

ren"l disorders

Treatment: yste"mine

or"lly or "s eyedro&s*


29/30

roth hormone

Other lysosomal disorders

Pycnodysostosis

(:600)

"the&sin A SA

(19:1)

Onset: G"rly childhood


linical !eatures: Short

st"ture* .ront"l "nd

occi&it"l &rominence*

del"yed closure o.

"nterior .ont"nel*

micron"thi"* n"rro

&"l"te* del"yed eru&tion

"nd &ersistence o.deciduous teeth*

hy&odonti"* "&l"si" or

hy&o&l"si" o. cl"5icles*

osteosclerosis*

susce&ti3ility to .r"cture*

scoliosis* s&ondylolysis*

3r"chyd"ctyly* roo5ed

n"ils


c"re* roth hormone

&ossi3ly hel&.ul


30/30

."ilure* de5elo&ment"l

dis"3ilities


c"re

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