Lysosomal enzymes break down macromolecules, either those from the cell itself (eg, when cellular structural components are being recycled) or those acquired outside the cell. Inherited defects or deficiencies of lysosomal enzymes (or other lysosomal components) can result in accumulation of undegraded metabolites. Because there are numerous specific deficiencies, storage diseases are usually grouped biochemically by the accumulated metabolite. Subgroups include
See also Approach to the Patient With a Suspected Inherited Disorder of Metabolism.
The most important are the mucopolysaccharidoses and sphingolipidoses. Type 2 glycogenosis is a lysosomal storage disorder, but most glycogenoses are not.
Because reticuloendothelial cells (eg, in the spleen) are rich in lysosomes, reticuloendothelial tissues are involved in a number of lysosomal storage disorders, but, generally, tissues richest in the substrate are most affected. Thus the brain, which is rich in gangliosides, is particularly affected by gangliosidoses, whereas mucopolysaccharidoses affect many tissues because mucopolysaccharides are present throughout the body.
Mucopolysaccharidoses (MPS)
MPS are inherited deficiencies of enzymes involved in glycosaminoglycan breakdown. Glycosaminoglycans (previously termed mucopolysaccharides) are polysaccharides abundant on cell surfaces and in extracellular matrix and structures. Enzyme deficiencies that prevent glycosaminoglycan breakdown cause accumulation of glycosaminoglycan fragments in lysosomes and cause extensive bone, soft tissue, and central nervous system changes. Inheritance is usually autosomal recessive (except for MPS type II).
Age at presentation, clinical manifestations, and severity vary by type (see table Mucopolysaccharidosis (MPS)). Common manifestations include coarse facial features, neurodevelopmental delays and regression, joint contractures, organomegaly, stiff hair, progressive respiratory insufficiency (caused by airway obstruction and sleep apnea), cardiac valvular disease, skeletal changes, and cervical vertebral subluxation.
Diagnosis of mucopolysaccharidoses is suggested by history, physical examination, bone abnormalities (eg, dysostosis multiplex) found during skeletal survey, and elevated total and fractionated urinary glycosaminoglycans. Diagnosis is confirmed by DNA analysis and/or enzyme analysis of cultured fibroblasts (prenatal) or peripheral white blood cells (postnatal). (See also testing for suspected inherited disorders of metabolism.) Additional testing is required to monitor organ-specific changes (eg, echocardiography for valvular disease, audiometry for hearing changes).
Mucopolysaccharidosis (MPS)
Disease (OMIM Number) | Defective Proteins or Enzymes | Comments |
|---|---|---|
MPS IH (Hurler syndrome; 607014*) MPS IS (Scheie syndrome; 607016*) MPS IH/S (Hurler-Scheie syndrome; 607015*) | Alpha-L-iduronidase | Onset: In IH, first year In IS, > 5 years In IH/S, 3–8 years Urine metabolites: 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: |
MPS II (Hunter syndrome; 309900*) | Iduronate sulfate sulfatase | Onset: 2–4 years Urine metabolites: Clinical features: Similar to Hurler 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: |
MPS III (Sanfilippo syndrome) | Onset: 2–6 years Urine metabolites: Clinical features: Similar to Hurler syndrome but with severe intellectual disability and mild somatic manifestations Treatment: Supportive care | |
Type IIIA (252900*) | Heparan N-sulfatase | |
Type IIIB (252920*) | Alpha-N-acetylglucosaminidase | |
Type IIIC (252930*) | Acetyl CoA:alpha-glucosaminide acetyltransferase | |
Type IIID (252940*) | N-acetylglucosaminine-6-sulfatase | |
MPS IV (Morquio syndrome) | Onset: 1–4 years Urine metabolites: Keratin sulfate; in IVB, also chondroitin 6-sulfate Clinical features: Similar to Hurler syndrome but with severe bone changes including odontoid hypoplasia; possibly normal intelligence Treatment: Supportive care | |
Type IVA (253000*) | Galactosamine-6-sulfate sulfatase | |
Type IVB (253010*) | Beta-galactosidase | |
MPS VI (Maroteaux-Lamy syndrome; 253200*) | N-Acetylgalactosamine-4sulfatase (arylsulfatase B) | Onset: Variable but can be similar to Hurler syndrome Urine metabolites: Dermatan sulfate Clinical features: Similar to Hurler syndrome but normal intelligence Treatment: |
MPS VII (Sly syndrome; 253220*) | Beta-glucuronidase | Onset: 1–4 years Urine metabolites: Dermatan sulfate, heparan sulfate, chondroitin 4-sulfate, chondroitin 6-sulfate Clinical features: Similar to Hurler syndrome but greater variation in severity Treatment: Supportive care, stem cell or bone marrow transplantation |
Onset: 6 months Urine metabolites: None Clinical features: Bilateral soft-tissue periarticular masses, dysmorphic features, short stature, normal intelligence Treatment: Not established | ||
* For complete gene, molecular, and chromosomal location information, see the Online Mendelian Inheritance in Man (OMIM) database. | ||
Sphingolipidoses
Sphingolipids are normal lipid components of cell membranes; they accumulate in lysosomes and cause extensive neuronal, bone, and other changes when enzyme deficiencies prevent their breakdown. Although incidence is low, carrier rate of some forms is high.
There are many types of sphingolipidosis (see table Some Sphingolipidoses); the most common sphingolipidosis is
Others sphingolipidoses include
Some Sphingolipidoses
Disease (OMIM Number) | Defective Proteins or Enzymes | Comments |
|---|---|---|
GM1 gangliosidosis, generalized | Ganglioside beta-galactosidase | |
Type I (infantile type; 230500*) | Type I onset: 0–6 months 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: 6–12 months 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; 230650*) | Type III onset: 3–50 years 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 months In type III, 2–6 years Urine metabolites: None Clinical features: Doll-like facies; cherry-red retina; early blindness; exaggerated startle reflex; initial hypotonia followed by hypertonia; psychomotor retardation followed by regression, seizures, and impaired sweating; in types I and II, death by age 5 years; death later in type III In type I, increased frequency in people of Ashkenazi Jewish ancestry Treatment: Supportive care | |
Type I (Tay-Sachs disease; 272800*) | Beta-hexosaminidase A | |
Type II (Sandhoff disease; 268800*) | Beta-hexosaminidase B | |
Type III (juvenile type) | Beta-hexosaminidase A | |
GM2 activator protein deficiency (Tay-Sachs disease AB variant, GM2A; 272750*) | GM2 activator protein | Onset, urine metabolites, and clinical features: Similar to Tay-Sachs Treatment: Supportive care, stem cell or bone marrow transplantation |
Niemann-Pick disease (see also Niemann-Pick disease types C and D in table Other Lipidoses) | Sphingomyelinase | |
Type A (257200*) | Onset:< 6 months 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 years 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 people of Ashkenazi Jewish ancestry Treatment: Supportive care, stem cell or bone marrow transplantation | |
Glucosylceramide beta-glucosidase | ||
Type I (adult or chronic form; 230800*) | Onset: Childhood to adulthood Urine metabolites: None Clinical features: Hepatosplenomegaly, osteolytic lesions with bone pain, avascular necrosis of the femoral head, vertebral compression, thrombocytopenia, anemia Increased frequency in people of Ashkenazi Jewish ancestry Treatment: Supportive care Splenectomy 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 years Treatment: Supportive care | |
Type III (juvenile form, Norrbottnian type; 231000*) | Onset: 4–8 years Urine metabolites: None Clinical features: Similar to type II except milder, possible survival into adulthood Treatment: | |
Farber disease (lipogranulomatosis; 228000*) | Ceramidase | Onset: First weeks of life Urine metabolites: Ceramide Clinical features: Lipogranulomatosis, 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 disease (301500*) | Onset: Childhood or adolescence Urine metabolites: Globosylceramide Clinical features: Painful crisis involving extremities and abdomen precipitated by stress, fatigue, or exercise; angiokeratoma; growth and pubertal delay; corneal dystrophy; renal failure; cardiomyopathy; myocardial infarction and heart failure, hypertension; lymphedema; obstructive lung disease; strokes; seizures; death Generally, only males affected but occasionally females Treatment: | |
Metachromatic leukodystrophy (250100*)
| Arylsulfatase A | Onset: For late infantile form, 1–2 years For juvenile form, 4 years to puberty 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 cerebrospinal fluid 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 in patients who have mildly symptomatic forms Therapeutic options under investigation, primarily in late infantile forms, include gene therapy, enzyme replacement therapy, substrate reduction therapy, and enzyme enhancement therapy |
Mucosulfatidosis (multiple sulfatase deficiency; 272200*) | Sulfatase-modifying factor-1 | 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 disease (245200*)
| Galactosylceramide beta-galactosidase | Onset: In infantile form, 3–6 months In late infantile and juvenile forms, 15 months–17 years In adult form, variable 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 cerebrospinal fluid protein; peripheral neuropathy; episodic fever In adult form, mentation generally preserved Treatment: Supportive care; bone marrow or stem cell transplantation for infantile and late infantile forms prolongs life span and improves functional abilities |
Sphingolipid activator protein deficiencies | Onset: Infancy to early childhood Urine metabolites: Sulfatides Clinical features: In saposin B deficiency, features similar to those of metachromatic leukodystrophy In saposin C deficiency, features similar to those of Gaucher 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 disease, consideration of enzyme replacement | |
Prosaposin deficiency (176801*) | Prosaposin | |
Saposin B deficiency (sulfatide activator deficiency) | Saposin B | |
Saposin C deficiency (Gaucher activator deficiency) | Saposin C | |
* For complete gene, molecular, and chromosomal location information, see the Online Mendelian Inheritance in Man (OMIM) database. | ||
MPS = mucopolysaccharidosis. | ||
Mucolipidoses and Other Lysosomal Disorders
In addition to mucolipidoses, there are many other lysosomal disorders including
Mucolipidosis (ML)
Disease (OMIM Number) | Defective Proteins or Enzymes | Comments |
|---|---|---|
ML I | See Sialidosis type I in table Oligosaccharidosis and Related Disorders | — |
ML II (I-cell disease; 252500*) | N-Acetylglucosaminyl-1-phosphotransfeerase catalytic subunit | Onset: First year of life Urine metabolites: No mucopolysaccharides Clinical features: Similar to Hurler syndrome but more severe; presence of phase-dense inclusion bodies in fibroblasts (I-cells) Treatment: Supportive care |
ML III (pseudo-Hurler polydystrophy) | N-Acetylglucosaminyl-1-phosphotransfeerase | Onset: 2–4 years Urine metabolites: None Clinical features: Similar to ML II but later onset and possible survival to adulthood Treatment: Supportive care |
Type III-A (252600*) | Catalytic subunit | |
Type III-C (252605*) | Substrate-recognition subunit | |
ML IV | See Sialolipidosis in table Oligosaccharidosis and Related Disorders | — |
* For complete gene, molecular, and chromosomal location information, see the Online Mendelian Inheritance in Man (OMIM) database. | ||
Other Lipidoses
Disease (OMIM Number) | Defective Proteins or Enzymes | Comments |
|---|---|---|
Niemann-Pick disease (see also Niemann-Pick disease, types A and B in table Some Sphingolipidoses) | Onset: Highly variable (early or late infancy, adolescence, adulthood) Urine metabolites: None Clinical features: Vertical gaze palsy, hepatosplenomegaly, neonatal jaundice, dysphagia, hypotonia 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 disease types A and B Earlier onset associated with faster progression and shorter lifespan Treatment: Hematopoietic stem cell transplantation may be effective in young patients with NPC2 mutations | |
Type C1/Type D (257220*) | NPC1 protein | |
Type C2 (607625*) | Epididymal secretory protein 1 (HE1; NPC2 protein) | |
| Lysosomal acid lipase | Onset: In Wolman disease, infancy In CESD, variable 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 disease, death during infancy if untreated In CESD, premature atherosclerosis Treatment: |
Cerebrotendinous xanthomatosis (cholestanol lipidosis; 213700*) | Sterol 27-hydroxylase | Onset: Adolescence Urine metabolites: Elevated 7-alpha-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: Chenodeoxycholic acid, statins |
Sitosterolemia (210250*, 618666*) | Microsomal HMG-CoA reductase ABC transporter proteins | Onset: First two decades of life Urine metabolites: None Clinical features: Atherosclerosis, premature coronary artery disease, abnormal red blood cells, xanthomas on tendons Treatment: Reducing intake of foods rich in plant fats |
Neuronal ceroid lipofuscinosis | Onset: In infantile form, 6–12 months In late infantile form, 2–4 years In juvenile forms (including CLN9), 4–10 years In adult form, 20–39 years In variant infantile forms, 4–7 years In progressive epilepsy form, 5–10 years Urine metabolites: None Clinical features: In infantile and late infantile forms, developmental delay, microcephaly, optic and cerebral atrophy, retinal degeneration, blindness, flexion contractures, hypotonia, ataxia, myoclonus, seizures, loss of speech, hyperexcitability, autofluorescence in neurons, granular osmiophilic deposits in cells, increased serum arachidonic acid, decreased linoleic acid In juvenile and adult forms, features of above forms plus extrapyramidal signs, progressive loss of walking ability, school and behavioral difficulties Treatment: Supportive care | |
Infantile form (CLN1, Santavuori-Haltia disease; 256730*) | Palmitoyl-protein thioesterase-1 | |
Late infantile form (CLN2, Jansky-Bielschowsky disease; 204500*) | Lysosomal pepstatin-insensitive peptidase | |
Juvenile form (CLN3, Batten disease, Vogt-Spielmeyer disease; 204200*) | Lysosomal transmembrane CLN3 protein | |
Adult form (CLN4, Kufs disease; 204300*) | Palmitoyl-protein thioesterase-1 | |
Variant late infantile form, Finnish type (CLN5; 256731*) | Lysosomal transmembrane CLN5 protein | |
Variant late infantile form (CLN6; 601780*) | Transmembrane CLN6 protein | |
Progressive epilepsy with intellectual disability (600143*) | Transmembrane CLN8 protein | |
CLN9 (609055*) | — | |
* For complete gene, molecular, and chromosomal location information, see the Online Mendelian Inheritance in Man (OMIM) database. | ||
Oligosaccharidosis and Related Disorders
Disease (OMIM Number) | Defective Proteins or Enzymes | Comments |
|---|---|---|
Sialidosis (256550*) | Neuraminidase 1 (sialidase) | |
Type I (cherry-red macular spot-myoclonus syndrome, mild form) | Onset: 8–25 years Urine metabolites: Increased sialyloligosaccharides 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, infantile, juvenile, and childhood forms) | Onset: In congenital form, in utero In infantile form, birth to 12 months In juvenile and childhood forms, 2–20 years 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 (Goldberg syndrome, combined neuraminidase and beta-galactosidase deficiency; 256540*)
| Protective protein/cathepsin A (PPCA) | Onset: In neonatal form, birth to 3 months In late infantile form, first year In juvenile/adult form, adolescence but with wide variability Urine metabolites: Elevated sialyloligosaccharides but 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 (phospholipidosis; mucolipidosis IV, Berman disease; 252650*) | Onset: First year 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, 3–12 months In type II, 1–4 years Urine metabolites: Mannose-rich 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 | |
Alpha-mannosidosis (248500*), type I (severe) or II (mild) | Alpha-D-mannosidase | |
Beta-mannosidosis (248510*) | Beta-D-mannosidase | Onset: 1–6 years Urine metabolites: Disaccharides, mannosyl-(1-4)-N-acetylglucosamine, heparan 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*)
| Alpha-L-fucosidase | Onset: In type I, 3–18 months In type II, 1–2 years Urine metabolites: Oligosaccharides 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 United States Treatment: Supportive care, consideration of bone marrow or stem cell transplantation |
Aspartylglucosaminuria (208400*) | N-Aspartylglucosaminidase | Onset: 2–6 years Urine metabolites: Aspartylglucosamine 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 (277950*) | Metalloproteinase-2 | 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 disease | N-Acetyl-galactosaminidase | |
Type I (infantile severe form; 609241*) | Onset: 8–15 months Urine metabolites: Oligosaccharides 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: Oligosaccharides 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 form; 609241*) | Onset: Childhood Urine metabolites: Oligosaccharides 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 of N-glycosylation (CDG), type I (pre-Golgi glycosylation defects) | Onset: Mostly infancy or childhood Clinical features Treatment: Supportive care | |
CDG Ia (solely neurologic and neurologic-multivisceral forms; 212065*) | Phosphomannomutase-2 | |
CDG Ib (602579*) | Mannose (Man) phosphate (P) isomerase | |
CDG Ic (603147*) | Dolichyl-P-Glc:Man(9)GlcNAc(2)-PP-dolichol glucosyltransferase | |
CDG Id (601110*) | Dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichol mannosyltransferase | |
CDG Ie (608799*) | Dolichyl-P-mannose synthase | |
CDG If (609180*) | Protein involved in mannose-P-dolichol utilization | |
CDG Ig (607143*) | Dolichyl-P-mannose:Man-7-GlcNAc-2-PP-dolichyl-alpha-6-mannosyltransferase | |
CDG Ih (608104*) | Dolichyl-P-glucose:Glc-1-Man-9-GlcNAc-2-PP-dolichyl-alpha-3-glucosyltransferase | |
CDG Ii (607906*) | Alpha-1,3-mannosyltransferase | |
CDG Ij (608093*) | UDP-GlcNAc:dolichyl-phosphate N-acetylglucosamine phosphotransferase | |
CDG Ik (608540*) | Beta-1,4-mannosyltransferase | |
CDG Il (608776*) | Alpha-1,2-mannosyltransferase | |
Congenital disorders of N-glycosylation, type II (Golgi defects) | Same as for type I, except isoelectric focusing of serum transferrin shows increased monosialotransferrin, disialotransferrin, trisialotransferrin, and asialotransferrin bands For type IIb, normal pattern | |
CDG IIa (212066*) | Mannosyl-alpha-1,6-glycoprotein-beta-1,2-N-acetylglucosminyltransferase | |
CDG IIb (606056*) | Glucosidase I | |
CDG IIc (Rambam-Hasharon syndrome; 266265*) | GDP-fucose transporter-1 | |
CDG IId (607091*) | Beta-1,4-galactosyltransferase | |
CDG IIe (608779*) | Oligomeric Golgi complex-7 | |
* For complete gene, molecular, and chromosomal location information, see the Online Mendelian Inheritance in Man (OMIM) database. | ||
Lysosomal Transport Defects
Disease (OMIM Number) | Defective Proteins or Enzymes | Comments |
|---|---|---|
Sialuria | ||
Infantile sialic acid storage disorder (269920*) | Sodium phosphate cotransporter | Onset: At birth Urine 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 year Treatment: Supportive care |
Finnish type (Salla disease; 604369*) | Sodium phosphate cotransporter | Onset: 6–9 months 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-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase | Onset: Infancy to early childhood Urine metabolites: Increased 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 (CLN3, CLN5, CLN6, CLN8) | See table Other Lipidoses | — |
Cystinosis | Cystinosin (lysosomal cystine transporter) | |
Infantile nephropathic form (219800*) | Onset: First year 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, white blood cells, and corneas Treatment: | |
Late-onset juvenile or adolescent form (219900*) | Onset: 12–15 years Urine metabolites: Renal Fanconi syndrome Clinical features: Similar to infantile form but milder Treatment: Similar to that for infantile form | |
Adult non-nephropathic form (219750*) | Onset: Early adolescence to adulthood Urine metabolites: Renal Fanconi syndrome Clinical features: Similar to infantile form but no renal disorders Treatment: | |
* For complete gene, molecular, and chromosomal location information, see the Online Mendelian Inheritance in Man (OMIM) database. | ||
Other Lysosomal Disorders
Disease (OMIM Number) | Defective Proteins or Enzymes | Comments |
|---|---|---|
Pycnodysostosis (265800*) | Cathepsin K | 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-5-phosphate storage disease (305920*) | ADP-ribose protein hydrolase | Onset: First year 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 (Pompe disease; 232300*) | See table Glycogen Storage Diseases and Disorders of Gluconeogenesis | — |
* For complete gene, molecular, and chromosomal location information, see the Online Mendelian Inheritance in Man (OMIM) database. | ||
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Online Mendelian Inheritance in Man (OMIM) database: Complete gene, molecular, and chromosomal location information
