Table 4

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Lysosomal Storage Disorders

Disease (OMIM
Number)

Defective Proteins Defective

Comments
or Enzymes
Genes
(Chromoso
mal
Location)

Mucopolysaccharidosis (MPS)

MPS I-H (Hurler's

syndrome; 607014)
MPS I-S (Scheie's
syndrome; 607016)
MPS I H/S (HurlerScheie syndrome;

-l-Iduronidase

IDUA
(4p16.3)*

Onset: In I-H, 1st yr

In I-S, > 5 yr
In I-H/S, 38 yr
Urine
metabolites:Dermatan
sulfate,heparin

607015)

sulfate
Clinical features:Corneal
clouding, stiff joints,
contractures, dysostosis
multiplex, coarse facies,
coarse hair,
macroglossia,
organomegaly,
intellectual disability with
regression, valvular heart
disease, hearing and
vision impairment,
inguinal and umbilical
hernia, sleep apnea,
hydrocephalus
Treatment: Supportive
care, enzyme
replacement, stem cell or

bone marrow
transplantation
MPS II (Hunter's
syndrome; 309900)

Iduronate sulfate

IDS (Xq28)*

sulfatase

Onset: 24 yr
Urine
metabolites:Dermatan
sulfate,heparin

sulfate
Clinical features:Similar
to Hurler's syndrome but
milder and no corneal
clouding
In mild form, normal
intelligence
In severe form,
progressive intellectual
and physical disability,
death before age 15
Treatment: Supportive
care, stem cell or bone
marrow transplantation
MPS III (Sanfilippo's

Onset: 26 yr

syndrome)
Type III-A (252900)

Urine
Heparan-S-sulfate
sulfamidase

Type III-B (252920)

N-acetyl-Dglucosaminidase

SGSH

metabolites:Heparin

(17q25.3)*
NAGLU
(17q21)*

sulfate
Clinical features:Similar
to Hurler's syndrome but

Type III-C (252930)

Acetyl-CoA-

(14)

with severe intellectual

glucosaminide N-

disability and mild

acetyltransferase

somatic manifestations

Type III-D (252940)

N-acetylglucosaminine-6-

GNS
(12q14)*
Treatment: Supportive care

sulfate sulfatase
MPS IV (Morquio's

Onset: 14 yr

syndrome
Type IV-A (253000)

Urine metabolites:Keratin
Galactosamine-6sulfate sulfatase

GALNS
(16q24.3)*

sulfate; in IV-B, also

chondroitin 6-sulfate
Clinical features:Similar

Type IV-B (253010)

-Galactosidase

GLB1

to Hurler's syndrome but

(3p21.33*

with severe bone

see also

changes including

GM1

odontoid hypoplasia;

gangliosido

possibly normal

sis, below)

intelligence
Treatment: Supportive
care

MPS VI (Maroteaux-

N-Acetyl

Lamy syndrome;

galactosamine -4-

253200)

sulfate sulfatase

ARSB (5q11q13)*

Onset: Variable but can be

similar to Hurler's
syndrome

(arylsulfatase B)

Urine
metabolites:Dermatan
sulfate
Clinical features:Similar
to Hurler's syndrome but
normal intelligence
Treatment: Supportive
care

MPS VII (Sly's

syndrome; 253220)

-Glucuronidase

GUSB
(7q21.11)*

Onset: 14 yr
Urine
metabolites:Dermatan
sulfate,heparin

sulfate, chondroitin 4-, 6sulfate

Clinical features:Similar
to Hurler's syndrome but
greater variation in
severity
Treatment: Supportive
care, stem cell or bone
marrow transplantation
MPS IX
(hyaluronidase

Hyaluronidase
deficiency

deficiency; 601492)

HYAL1
(3p21.3p21.2)*

Onset: 6 mo
Urine metabolites:None
Clinical features:Bilateral
soft-tissue periarticular
masses, dysmorphic
features, short stature,
normal intelligence
Treatment: Not
established

Mucolipidosis (ML)

ML I

See Sialidosis type I

(below)

ML II (I-cell disease;
252500)

N-Acetylglucosaminyl1phosphotransfeerase
catalytic subunit

GNPTA
(4q21-q23)

Onset: 1st yr
Urine metabolites: No
mucopolysaccharides
Clinical features:Similar
to Hurler's syndrome but
more severe; presence of
phase-dense inclusion
bodies in fibroblasts (Icells)
Treatment: Supportive
care

ML III (pseudo-

N-acetylglucosaminyl-

Hurler's

1-

polydystrophy)

phosphotransfeerase

Type III-A (252600)

Catalytic subunit

Onset: 24 yr
Urine metabolites:None
Clinical features:Similar
GNPTA
(4q21-q23)*

to ML II but later onset

and possible survival to
adulthood

Type III-C (252605)

Substrate-recognition
subunit

ML IV

See Sialolipidosis

GNPTAG
(16p)*

Treatment: Supportive
care

GLB1

(below)
Sphingolipidosis

GM1 gangliosidosis,
generalized

Ganglioside galactosidase

(3p21.33*;
allelic to

Type I (230500)

MPS IVB)

Type I onset: 06 mo
Urine metabolites:None
Clinical features:Coarse
facies; clear cornea,
cherry-red macular spot,
gingival hyperplasia,
organomegaly,
dysostosis multiplex,
hypertrichosis,
angiokeratoma corporis
diffusum, cerebral
degeneration; death in
infancy
Treatment: Supportive
care

Type II (juvenile type;

230600)

Type II onset: 612 mo

Urine metabolites:None
Clinical features: Gait
disturbance, spasticity,

dystonia, loss of
psychomotor milestones,
mild visceromegaly and
bone abnormality
Treatment: Supportive
care
Type III (adult type;

Type III onset: 350 yr

230650)

Urine metabolites:None
Clinical
features:Angiokeratoma
corporis diffusum,
spondyloepiphyseal
dysplasia, dysarthria,
cerebellar dysfunction; no
macular red spots or
visceromegaly
Treatment: Supportive
care

GM2 gangliosidosis

Onset: In types I and II, 5

6 mo

Type I (Tay-Sachs

-Hexosaminidase A

disease; 272800)

HEXA
(15q23q24)*

In type III, 26 yr
Urine metabolites:None
Clinical features: Doll-like

Type II (Sandhoff's

-Hexosaminidase B

disease; 268800)
Type III (juvenile
type)

HEXB
(5q13)*

-Hexosaminidase A

facies; cherry-red retina;

early blindness;
exaggerated startle
reflex; initial hypotonia
followed by hypertonia;
psychomotor retardation
followed by regression,
seizures, and impaired
sweating; death by age 5
yr
In type I, increased

frequency in Ashkenazi
Jews
GM2 activator protein GM2 activator protein

GM2A

Treatment: Supportive

deficiency (Tay-

(5q31.3-

care, stem cell or bone

Sachs disease AB

q33.1)*

marrow transplantation

variant, GM2A;

Same as that for GM2

272750)

types I and II

Niemann-Pick

Sphingomyelinase

SMPD1

disease (see also

(11p15.4-

Niemann-Pick

p15.1)*

disease types C and

D, below)
Type A (257200)

Onset:< 6 mo
Clinical features:Growth
delay, cherry-red retina,
frequent respiratory
infections,
hepatosplenomegaly,
vomiting, constipation,
osteoporosis,
lymphadenopathy,
hypotonia followed by
spasticity, sea-blue
histiocytes on tissue
biopsies, large
vacuolated foam cells in
bone marrow (NP cells),
death by age 3 yr
Treatment: Supportive
care, stem cell or bone
marrow transplantation

Type B (607616)

Onset: Variable

Clinical features: Much

milder symptoms, no
neurologic involvement,
survival to adulthood
Increased frequency in
Ashkenazi Jews
Treatment: Supportive
care, stem cell or bone
marrow transplantation
Gaucher's disease

Glucosylceramide -

GBA (1q21)*

glucosidase
Type I (adult or
chronic form;
230800)

Onset: Childhood or
adolescence
Urine metabolites:None
Clinical
features:Hepatosplenom
egaly, osteolytic lesions
with bone pain, avascular
necrosis of the femoral
head, vertebral
compression,
thrombocytopenia,
anemia
Increased frequency in
Ashkenazi Jews
Treatment: Supportive
care, splenectomy,
enzyme replacement,
bone marrow or stem cell
transplantation

Type II (infantile form;

230900)

Onset: Infancy
Urine metabolites:None
Clinical features:Infantile
hydrops,

hepatosplenomegaly,
dysphagia, bone lesions,
hypertonicity,
pseudobulbar palsy,
laryngeal spasm,
ichthyosis,
developmental delay,
hypersplenism, death by
age 2 yr
Treatment: Supportive
care
Type III (juvenile

Onset: 48 yr

form, Norrbottnian

Urine metabolites:None

type; 231000)

Clinical features:Similar
to type II except milder,
possible survival into
adulthood
Treatment: Supportive
care

Farber's disease
(lipogranulomatosis;
228000)

Ceramidase

ASAH (8p22- Onset: First weeks of life

p21.3)*

Urine
metabolites:Ceramide
Clinical
features:Lipogranulomat
osis, periarticular
subcutaneous nodules,
irritability, hoarse cry,
psychomotor and growth
delay, respiratory
insufficiency, histiocytosis
in multiple tissues,
nephropathy,
hepatosplenomegaly,
cherry-red macular spot

Milder variants sometimes

divided into 7 subtypes
according to severity
Treatment: Supportive
care
Fabry's disease
(301500)

Trihexosylceramide -

GLA (Xq22)*

galactosidase

Onset: Childhood or
adolescence
Urine
metabolites:Globosylcer
amide
Clinical features:Painful
crisis involving
extremities and abdomen
precipitated by stress,
fatigue, or exercise;
angiokeratoma; growth
and pubertal delay;
corneal dystrophy; renal
failure; cardiomyopathy;
MI and heart failure,
hypertension;
lymphedema; obstructive
lung disease; strokes;
seizures; death
Generally, only males
affected but occasionally
females
Treatment: Supportive
care, enzyme
replacement

Metachromatic
leukodystrophy
(250100)

Arylsulfatase A

ARSA
(22q13.31)*

Onset: For late infantile

form, 12 yr
For juvenile form, 4 yr to
puberty

Late infantile
form

Juvenile form

Adult form

Pseudodeficien
cy form

For adult form, any age

after puberty
Urine
metabolites:Sulfatides
Clinical features: Optic
atrophy, gall bladder
dysfunction, urinary
incontinence, hypotonia,
gait disturbance,
hyporeflexia followed by
hyperreflexia, bulbar
palsies, ataxia, chorea,
demyelination and
developmental
regression, increased
CSF protein
In adult form, also
schizophrenia-like
symptoms
pseudodeficiency
characterized by mild
decrease in enzyme
activity without neurologic
degeneration
Treatment: Supportive
care, consideration of
bone marrow or stem cell
transplantation

Mucosulfatidosis
(multiple sulfatase
deficiency; 272200)

Sulfatase-modifying
factor-1

SUMF1
(3p26)*

Onset: Infancy
Urine
metabolites:Sulfatides,
mucopolysaccharides
Clinical features:Similar
to late infantile form of
metachromatic

leukodystrophy, plus
ichthyosis and dysostosis
multiplex
Treatment: Supportive
care
Krabbe's disease
(245200)

Galactosylceramide - GALC
galactosidase

(14q31)*

Onset: In infantile form, 3

6 mo
In late infantile and

Infantile form

juvenile forms, 15 mo17

Late infantile
form

yr

Juvenile form

In adult form, variable

Adult form

Urine metabolites: None

Clinical features:Growth
delay, developmental
delay followed by
regression, deafness,
blindness, vomiting,
hyperirritability,
hypersensitivity to stimuli,
increased deep-tendon
reflex, and spasticity;
seizures; diffuse cerebral
atrophy and
demyelination; elevated
CSF protein; peripheral
neuropathy; episodic
fever
In adult form, mentation
generally preserved
Treatment: Supportive
care, bone marrow or
stem cell transplantation

Sphingolipid activator
protein deficiencies

Onset: Infancy to early

childhood

Prosaposin deficiency Prosaposin

(176801)
Saposin B deficiency

PSAP
(10q22.1)*

Saposin B

(sulfatide activator

PSAP
(10q22.1)*

deficiency)
Saposin C deficiency

Urine
metabolites:Sulfatides
Clinical features: In
saposin B deficiency,
features similar to those
of metachromatic

Saposin C

(Gaucher's activator

PSAP
(10q22.1)*

leukodystrophy
In saposin C deficiency,
features similar to those

deficiency)

of Gaucher's disease
type III
In prosaposin deficiency,
features of saposin B and
C deficiencies
Treatment: Supportive
care; consideration of
bone marrow or stem cell
transplantation; for
features of Gaucher's
disease, consideration of
enzyme replacement
Other lipidoses

Niemann-Pick

Onset: Highly variable

disease (see also

(early or late infancy,

Niemann-Pick

adolescence, adulthood)

disease, types A

Urine metabolites:None

and B, above)
Type C1/Type D

Clinical features:Vertical
NPC1 protein

((257220)

NPC1

gaze palsy,

(18q11-

hepatosplenomegaly,

q12)*

neonatal jaundice,
dysphagia, hypotonia

Type C2 (607625)

Epididymal secretory
protein 1 (HE1;
NPC2 protein)

NPC2
(14q24.3)*

followed by spasticity,
seizures, cerebellar
ataxia, dysarthria,
psychomotor delay and

degeneration, psychosis
and behavioral problem,
fetal ascites, foam cells
and sea-blue histiocytes
as in Niemann-Pick
Lysosomal acid lipase Lysosomal acid lipase
deficiency (278000)

LIPA (10q24q25)*

disease types A and B

Onset: In Wolman's
disease, infancy
In CESD, variable

Wolman's
disease

Cholesteryl
ester storage
disease
(CESD)

Urine metabolites:None
Clinical features:Growth
failure; vomiting;
diarrhea; steatorrhea;
hepatosplenomegaly;
hepatic fibrosis;
pulmonary hypertension;
adrenal calcification;
xanthomatous changes in
liver, adrenal glands,
lymph nodes, bone
marrow, small intestine,
lungs, and thymus;
hypercholesterolemia
and normal to elevated
plasma lipids; foam cells
in marrow
In Wolman's disease,
death during infancy
In CESD, premature
atherosclerosis

Treatment: For Wolman's

disease, no effective
therapy
For CESD, statins plus a
low-cholesterol diet
helpful
Cerebrotendinous

Sterol 27-hydroxylase

xanthomatosis

CYP27A

Onset: Adolescence

(2q33-qter)* Urine

(cholestanol

metabolites:Elevated 7-

lipidosis; 213700)

-hydroxylated bile
alcohol
Clinical features:Juvenile
cataracts, tendon and
skin xanthomas,
xanthelasma, fractures,
atherosclerosis,
dementia, spinal cord
paresis, cerebellar ataxia,
developmental disability,
pseudobulbar paralysis,
leukodystrophy,
peripheral neuropathy
Treatment:Chenodeoxych
olic acid, statins

Neuronal ceroid

Onset: In infantile form, 6

lipofuscinosis

12 mo

Infantile form (CLN1,

Palmitoyl-protein

Santavuori-Haltia

thioesterase-1

PPT1 (1p32)*

In late infantile form, 24

yr
In juvenile forms (including

disease; 256730)

CLN9), 410 yr
Late infantile form
(CLN2, JanskyBielschowsky
disease; 204500)

Lysosomal pepstatininsensitive peptidase

CLN2
(11p15.5)*

In adult form, 2039 yr

In variant infantile forms,
47 yr

Juvenile form (CLN3,

Lysosomal

Batten disease,

transmembrane

Vogt-Spielmeyer

CLN3 protein

CLN3
(16p12.1)*

In progressive epilepsy
form, 510 yr

disease; 204200)
Adult form (CLN4,
Kufs' disease;

Palmitoyl-protein

PPT1 (1p32)*

thioesterase-1

204300)
Variant late infantile

Lysosomal

CLN5

form, Finnish type

transmembrane

(13q21-

(CLN5; 256731)

CLN5 protein

q32)*

Variant late infantile

form (CLN6;

Transmembrane CLN6 CLN6

protein

601780)
Progressive epilepsy
with intellectual

(15q21q23)*

Transmembrane CLN8 CLN8 (8pterprotein

p22)*

Urine metabolites:None
Clinical features: In

disability (600143)

infantile and late infantile

CLN9 (609055)

forms, developmental
delay, microcephaly, optic
and cerebral atrophy,
retinal degeneration,
blindness, flexion
contractures, hypotonia,
ataxia, myoclonus,
seizures, loss of speech,
hyperexcitability,

Oligosaccharidosis and related disorders

Sialidosis (256550)

Neuraminidase 1
(sialidase)

Type I (cherry-red
macular spot-

NEU1
(6p21.3)*
Onset: 825 yr
Urine

myoclonus

metabolites:Increased

syndrome, mild

sialyloligosaccharides

form)

Clinical features:Cherry-

red macular spot,

insidious vision loss,
cataracts, progressive
myoclonus and ataxia,
normal intelligence,
increased deep tendon
reflex
Treatment: Supportive
care
Type II (congenital,

Onset: In congenital form,

infantile, juvenile,

in utero

and childhood

In infantile form, birth to 12

forms)

mo
In juvenile and childhood
forms, 220 yr
Urine
metabolites:Increased
sialyloligosaccharides
Clinical features: All of
features of type I plus
coarse facies, hypotonia,
hepatomegaly, ascites,
inguinal hernia, growth
delay, muscle wasting,
laryngomalacia,
dysostosis multiplex
Treatment: Supportive
care

Galactosialidosis

Protective

(Goldberg's

protein/cathepsin A

syndrome,

(PPCA)

combined
neuraminidase
and -galactosidase

PPGB
(20q13.1)*

Onset: In neonatal form,

birth to 3 mo
In late infantile form, 1st
mo
In juvenile/adult form,
adolescence but with

deficiency; 256540)

wide variability

Urine

Neonatal form

metabolites:Elevated

Late infantile
form

sialyloligosaccharides but

Juvenile/adult
form

no free sialic acid

Clinical features:Coarse
facies, corneal clouding,
cherry-red macular spot,
intellectual disability,
seizures, dysostosis
multiplex, hearing loss,
hemangiomas, valvular
heart disease
Treatment: Supportive
care

Sialolipidosis

MCOLN1

(phospholipidosis;

(19p13.3-

mucolipidosis IV,

p13.2)*

Berman disease;
252650)

Onset: 1st yr
Urine metabolites: No
mucopolysaccharides
Clinical features:Severe
(Berman disease) and
mild forms
Developmental delay,
corneal opacities, visual
deficiency, strabismus,
hypotonia, increased
deep tendon reflexes; no
radiographic skeletal
abnormality,
macrocephaly, or
organomegaly
Treatment: Supportive
care

Mannosidosis

Onset: In type I, 312 mo

-Mannosidosis

-D-Mannosidase

MAN2B1

(248500), type I

(19cen-

(severe) or II (mild)

q12)*

In type II, 14 yr
Urine
metabolites:Mannoserich oligosaccharides
Clinical features:Coarse
facies, macrocephaly,
macroglossia, cataracts,
gingival hypertrophy,
slight
hepatosplenomegaly,
dysostosis multiplex,
hypotonia, hearing loss,
bowed femur,
pancytopenia, recurrent
respiratory infections,
immunodeficiency and
autoimmunity,
developmental disabilities
Treatment: Supportive
care, consideration of
bone marrow or stem cell
transplantation

-Mannosidosis
(248510)

-D-Mannosidase

MANBA

Onset: 16 yr

(4q22-q25)* Urine
metabolites:Disaccharid
es, mannosyl-(1-4)-Nacetylglucosamine,hepari
n

sulfate
Clinical features:Coarse
facies, deafness, delayed
speech, hyperactivity,
genital angiokeratoma,

tortuous conjunctival
vessels
Treatment: Supportive
care, consideration of
bone marrow or stem cell
transplantation
Fucosidosis (230000) -L-Fucosidase

(1p34)*

Type I (severe
infantile form)

Onset: In type I, 318 mo

In type II, 12 yr
Urine
metabolites:Oligosaccha

FUCA1

Type II (mild
form)

rides
Clinical features: Short
stature, growth delay,
coarse facies,
macroglossia,
cardiomegaly, recurrent
respiratory infections,
dysostosis multiplex,
hernias,
hepatosplenomegaly,
angiokeratoma,
anhidrosis and elevated
sweat chloride,
developmental disability,
hypotonia changing to
hypertonia, cerebral
atrophy, seizures, spastic
quadriplegia, vacuolated
lymphocytes
Most patients from Italy or
southwestern US
Treatment: Supportive
care, consideration of
bone marrow or stem cell
transplantation

Aspartylglucosaminur Nia (208400)

Aspartylglucosaminid

AGA (4q32q33)*

ase

Onset: 26 yr
Urine
metabolites:Aspartylgluc
osamine
Clinical features:Growth
delay, microcephaly,
cataracts, coarse facies,
macroglossia, mitral
insufficiency,
hepatomegaly, diarrhea,
hernias, recurrent
respiratory infections,
macro-orchidism, mild
dysostosis multiplex,
angiokeratoma corporis
diffusum, acne,
developmental
disabilities, hypotonia,
spasticity, cerebral
atrophy, seizures, speech
delay, hoarse voice
Increased frequency in
Finnish populations
Treatment: Supportive
care, consideration of
bone marrow or stem cell
transplantation

Winchester syndrome Metalloproteinase-2

(277950)

MMP2
(16q13)*

Onset: Early infancy

Urine metabolites:None
Clinical features: Short
stature, coarse facies,
corneal opacities,
gingival hyperplasia, joint
contractures,
osteoporosis,

kyphoscoliosis, vertebral
compression, carpotarsal
osteolysis, ankylosis of
small joints of feet,
diffuse thickened skin,
hyperpigmentation,
hypertrichosis
Treatment: Supportive
care
Schindler's disease

N-Acetylgalactosaminidase

Type I (infantile
severe form;
609241)

-NAGA
(22q13)*
Onset: 815 mo
Urine
metabolites:Oligosaccha
rides and O-linked
sialopeptides
Clinical features:Cortical
blindness, optic atrophy,
nystagmus, strabismus,
osteopenia, joint
contracture, muscular
atrophy, developmental
delay and regression,
myoclonus, seizures,
spasticity, hyperreflexia,
decorticate posturing,
neuraxonal dystrophy
Treatment: Supportive
care

Type II (Kanzaki
disease, adult-onset
form; 609242)

Onset: Adulthood
Urine
metabolites:Oligosaccha
rides and O-linked
sialopeptides

Clinical features:Coarse
facies, deafness,
conjunctival and retinal
vascular tortuosity,
angiokeratoma corporis
diffusum, telangiectasia,
lymphedema, mild
intellectual impairment,
peripheral axonal
neuropathy
Treatment: Supportive
care
Type III (intermediate

Onset: Childhood

form; 609241)

Urine
metabolites:Oligosaccha
rides and O-linked
sialopeptides
Clinical
features:Intermediate
between types I and II;
variable and ranging from
seizures and moderate
psychomotor retardation
to mild autistic features
with speech and
language delay
Treatment: Supportive
care

Congenital disorders

Onset: Mostly infancy or

ofN-glycosylation,

childhood

type I (pre-Golgi

Clinical features (some or

glycosylation

most of the following):

defects)

Growth failure, prominent

CDG Ia (solely

Phosphomannomutas

PMM2

forehead with large ears,

neurologic and

e-2

neurologic-

(16p13.3-

high-arched or cleft palate,

p13.2)*

strabismus, retinitis

multivisceral forms;

pigmentosa, pericardial

212065)

effusion, cardiomyopathy,
hepatomegaly, vomiting,

CDG Ib (602579)

Mannose (Man)
phosphate (P)

MPI (15q22qter)*

isomerase
CDG Ic (603147)

Dolicho-PGlc:Man9GlcNAc2-

ALG6
(1p22.3)*

Man:Man5GlcNAc2-

ALG3
(3q27)*

synthase

contractures, ectopic fat

hypotonia, strokelike
episodes, seizures,
olivopontine hypoplasia,
peripheral neuropathy,

mannosyltransferase
Dolichol-P-mannose

kyphosis, joint

muscle weakness,

PP-dolichol

CDG Ie (608799)

proximal tubulopathy,

pads, orange-peel skin,

glucosyltransferase
Dolicho-P-

primary ovarian failure,

renal cysts, nephrosis,

PP-dolichol

CDG Id (601110)

diarrhea, liver fibrosis,

hypothyroidism,
DPM1
(20q13.31)*

hyperinsulinism, factor XI
deficiency, antithrombin III
deficiency,

CDG If (609180)

Protein involved in

MPUD1

thrombocytosis,

mannose-P-dolichol

(17p13.1-

decreased IgA and IgG,

utilization

p12)*

leukocyte adhesion defect

(in type IIc),

CDG Ig (607143)

CDG Ih (608104)

Dolichyl-P-

ALG12 (22)*

mannose:Man-7-

hypocholesterolemia,

GlcNAc-2-PP-

increased

dolichyl--6-

disialotransferrin and

mannosyltransferase

asialotransferrin bands

Dolichyl-P-

ALG8

glucose:Glc-1-Man-

(11pter-

9-GlcNAc-2-PP-

p15.5)*

dolichyl--3glucosyltransferase
CDG Ii (607906)

hypoalbuminemia,

-1,3-

ALG2

when isoelectric focusing

of serum transferrin is
done
Treatment: Supportive care

CDG Ij (608093)

Mannosyltransferase

(9q22)*

UDP-GlcNAc:dolichyl-

DPAGT1

P NAcGlc

(11q23.3)*

phosphotransferase
CDG Ik (608540)

-1,4Mannosyltransferase

CDG Il (608776)

-1,2Mannosyltransferase

ALG1
(16p13.3)*
ALG9
(11q23)*

Congenital disorders

Same as for type I, except

ofN-glycosylation,

isoelectric focusing of

type II (Golgi

serum transferrin shows

defects)

increased
monosialotransferrin,

CDG IIa (212066)

Mannosyl--1,6glycoprotein--1,2-N-

MGAT2
(14q21)*

acetylglucosminyltran

Glucosidase I

For type IIb, normal

GCS1 (1p13p12)*

CDG IIc (RambamHasharon

GDP-fucose
transporter-1

FUCT1
(11p11.2)*

syndrome; 266265
CDG IId (607091)

-1,4Galactosyltransferas

B4GALT1
(9p13)*

e
CDG IIe (608779)

Oligomeric Golgi
complex-7

Lysosomal transport defects

Sialuria

trisialotransferrin, and
asialotransferrin bands

sferase
CDG IIb (606056)

disialotransferrin,

COG7 (16p)*

pattern

Infantile sialic acid

Na phosphate

storage disorder

cotransporter

SLC17A5

Onset: At birth

(6q14-q15)* Urine

(269920)

metabolites:Increased
free sialic acid
Clinical features:Growth
failure, coarse facial
features, dysostosis
multiplex, nystagmus,
ptosis, gingival
hypertrophy,
cardiomegaly, heart
failure,
hepatosplenomegaly,
nephrosis, death at about
age 1 yr
Treatment: Supportive
care

Finnish type (Salla

Na phosphate

disease; 604369)

cotransporter

SLC17A5

Onset: 69 mo

(6q14-q15)* Urine
metabolites:Increased
free sialic acid
Clinical features:Growth
failure, developmental
disability, ataxia,
hypotonia, hypotonia,
spasticity, dyspraxia,
dysarthria, seizures, gait
problems, athetosis;
increased frequency in
Finland
Treatment: Supportive
care

French type (269921) UDP-Nacetylglucosamine-2-

GNE (9p12p11)*

Onset: Infancy to early

childhood

epimerase/N-

Urine

acetylmannosamine

metabolites:Increased

kinase

free sialic acid

Clinical features:Coarse
facies with normal
growth, developmental
delay, sleep apnea,
hypoplastic nipples,
hepatosplenomegaly,
inguinal hernias,
generalized hirsutism,
seizures
Treatment: Supportive
care

Neuronal ceroid
lipofuscinosis

See Other lipidoses,

above

(CLN3, CLN5,
CLN6, CLN8)
Cystinosis

Cystinosin (lysosomal
cystine transporter)

Infantile nephropathic
form (219800)

CTNS
(17p13)*
Onset: 1st yr
Urine metabolites:Renal
Fanconi syndrome
Clinical features:Growth
failure, frontal bossing,
photophobia, peripheral
retinopathy with
decreased acuity, corneal
crystals and erosion,
rickets,
hepatosplenomegaly,
pancreatic insufficiency,
renal calculi, renal failure,
renal Fanconi syndrome,
decreased sweating,

myopathy, dysphagia,
cerebral atrophy, normal
intelligence but
neurologic deterioration
in long-term survivors
Cystine accumulation
throughout
reticuloendothelial
system, WBC, and
cornea
Treatment:Replacement
therapy for Fanconi
syndrome, renal
transplant for failure,
cysteamine orally or as
eyedrops, growth
hormone
Late-onset juvenile
form (219900)

Onset: 1215 yr
Urine metabolites:Renal
Fanconi syndrome
Clinical features:Similar
to infantile form but
milder
Treatment: Similar to that
for infantile form

Adult nonnephropathic form

(219750)

Onset: Early teens to

adulthood
Urine metabolites:Renal
Fanconi syndrome
Clinical features:Similar
to infantile form but no
renal disorders
Treatment: Cysteamine
orally or as eyedrops,

growth hormone
Other lysosomal disorders

Pycnodysostosis

Cathepsin K

(265800)

CTSK
(1q21)*

Onset: Early childhood

Urine metabolites:None
Clinical features: Short
stature, frontal and
occipital prominence,
delayed closure of
anterior fontanel,
micrognathia, narrow
palate, delayed eruption
and persistence of
deciduous teeth,
hypodontia, aplasia or
hypoplasia of clavicles,
osteosclerosis,
susceptibility to fracture,
scoliosis, spondylolysis,
brachydactyly, grooved
nails
Treatment: Supportive
care, growth hormone
possibly helpful

Glutamyl ribose-5phosphate storage

disease (305920)

ADP-ribose protein
hydrolase

Onset: 1st yr
Urine
metabolites:Proteinuria
Clinical features:Coarse
facies, hypotonia, muscle
wasting and atrophy, loss
of speech and vision,
seizures, neurologic
deterioration, optic
atrophy, nephrosis,
hypertension, renal

failure, developmental
disabilities
Treatment: Supportive
care
Glycogen storage
disease type 2

See
Table2sec19ch296

(Pompe's disease)
*Gene has been identified, and molecular basis has been elucidated.
OMIM = online mendelian inheritance in man (see database at http://www.ncbi.nlm.nih.gov/omim).

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