Cause
- Lysosomal enzyme deficiency → accumulation of abnormal metabolic products.
- ↑ incidence of Tay-Sachs, Niemann-Pick, and some forms of Gaucher disease in Ashkenazi Jews.
Major lysosomal storage disease
Disease | Findings | Deficient enzyme | Accumulated substrate | Inheritance | Clinical features |
Sphingolipidoses | ㅤ | ㅤ | ㅤ | ㅤ | ㅤ |
Tay-Sachs disease | Progressive neurodegeneration, developmental delay, hyperreflexia, hyperacusis, cherry-red spot on macula A (lipid accumulation in ganglion cell layer), lysosomes with onion skin, no hepatosplenomegaly (vs Niemann-Pick). | (1) Hexosaminidase A ("Tay-Sax") | GM₂ ganglioside | AR | ㅤ |
Fabry disease | Early: triad of episodic peripheral neuropathy, angiokeratomas B, hypohidrosis. Late: progressive renal failure, cardiovascular disease. | (2) α-galactosidase A | Ceramide trihexoside (globotriaosylceramide) | XR | ㅤ |
Gaucher disease | Most common. Hepatosplenomegaly, pancytopenia, osteoporosis, avascular necrosis of femur, bone crises, Gaucher cells (lipid-laden macrophages resembling crumpled tissue paper). | (5) Glucocerebrosidase (β-glucosidase); treat with recombinant glucocerebrosidase | Glucocerebroside | AR | ㅤ |
Niemann-Pick disease | (6) Sphingomyelinase | Sphingomyelin | AR | ㅤ | |
Leukodystrophies | ㅤ | ㅤ | ㅤ | ㅤ | ㅤ |
Metachromatic leukodystrophy | Central and peripheral demyelination with ataxia, dementia. | (3) Arylsulfatase A | Cerebroside sulfate | AR | ㅤ |
Krabbe disease | Peripheral neuropathy, destruction of oligodendrocytes, developmental delay, CN II atrophy, globoid cells. | (4) Galactocerebrosidase (galactosylceramidase) | Galactocerebroside, psychosine | AR | ㅤ |
Mucopolysaccharidoses | ㅤ | ㅤ | ㅤ | ㅤ | ㅤ |
Hurler syndrome | Developmental delay, hirsutism, skeletal anomalies, airway obstruction, clouded cornea, hepatosplenomegaly. | α-L-iduronidase | Heparan sulfate, dermatan sulfate | AR | Dwarfism, facial dysmorphism (Gargolylsm), mental retardation, Kyphosis, hearing loss, death by age 10 from respiratory/cardiac complications. |
Hunter syndrome | Mild Hurler + aggressive behavior, no corneal clouding. | Iduronate-2-sulfatase | Heparan sulfate, dermatan sulfate | XR | Facial deformity, mild mental retardation, no cardiomegally, no Kyphosis, hearing loss, Mongolian blue spot, X-linked recessive. |
Sanfilippo syndrome | ㅤ | 4 different types of enzyme, different types giving 4 types | Heparan sulfate | AR | Learning difficulties and behavioural problems, Dementia → vegetative → death |
Sanfilippo syndrome A | Initially symptom-free, then progressive intellectual decline/speech delay, hyperactivity and sleep disturbance followed by motor disease. Death in third decade. | Heparan sulfamidase | Heparan sulfate | ㅤ | ㅤ |
Sanfilippo syndrome B | ㅤ | N-Acetylglucosaminidase | ㅤ | ㅤ | ㅤ |
Sanfilippo syndrome C | ㅤ | Heparan-α-glucosaminide N-acetyltransferase | ㅤ | ㅤ | ㅤ |
Sanfilippo syndrome D | ㅤ | N-Acetylglucosamine-6-sulfatase | ㅤ | ㅤ | ㅤ |
Morquio syndrome | Severe skeletal dysplasia • Incompetence of the odontoid process • Os odontoideum short stature, cord compression, cardiac abnormalities, corneal clouding, death early age | Galactose-6-sulfate sulfatase | Keratan sulfate | AR | ㅤ |
Morquio syndrome A | Severe skeletal dysplasia, short stature, cord compression, cardiac abnormalities, corneal clouding, death at an early age. | Galactose-6-sulfate sulfatase | Keratan sulfate, chondroitin 6-sulfate | ㅤ | ㅤ |
Morquio syndrome B | ㅤ | β-Galactosidase | Keratan sulfate | ㅤ | ㅤ |
Maroteaux-Lamy syndrome | Normal intellectual development, but shares features of Hurler syndrome. | N-Acetylgalactosamine-4-sulfatase | Dermatan sulfate | ㅤ | ㅤ |
Sly syndrome | Hydrops fetalis but those that survive to birth have similar to Hurler syndrome | β-glucoronidase | Heparan sulfate, dermatan sulfate, chondroitin 6-sulfate | ㅤ | ㅤ |
Natowicz syndrome | Short stature, periarticular soft tissue masses | Hyaluronidase | Hyaluronic acid | ㅤ | ㅤ |
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