# Sphingolipidoses

Sphingolipidoses are a class of lipid storage disorders or degenerative storage disorders caused by deficiency of an enzyme that is required for the catabolism of lipids that contain ceramide, also relating to sphingolipid metabolism. The main members of this group are Niemann–Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay–Sachs disease and metachromatic leukodystrophy. They are generally inherited in an autosomal recessive fashion, but notably Fabry disease is X-linked recessive. Taken together, sphingolipidoses have an incidence of approximately 1 in 10,000, but substantially more in certain populations such as Ashkenazi Jews. Enzyme replacement therapy is available to treat mainly Fabry disease and Gaucher disease, and people with these types of sphingolipidoses may live well into adulthood. The other types are generally fatal by age 1 to 5 years for infantile forms, but progression may be mild for juvenile- or adult-onset forms.

## Accumulated products

* Gangliosides: Gangliosidosis
** GM1 gangliosidoses
** GM2 gangliosidoses
*** Tay–Sachs disease
*** Sandhoff disease
*** GM2-gangliosidosis, AB variant
* Glycolipids
** Fabry's disease
** Krabbe disease
** Metachromatic leukodystrophy
* Glucocerebrosides
** Gaucher's disease

## Comparison

Comparison of the main sphingolipidoses :
| Disease | Deficient enzyme | Accumulated products | Symptoms | Inheritance | Incidence | Generally accepted treatments | Prognosis |
| Niemann-Pick disease | Sphingomyelinase | Sphingomyelin in brain and RBCs | Mental retardation Spasticity Seizures Hepatosplenomegaly Thrombocytopenia Ataxia | Autosomal recessive | 1 in 100,000 | Limited | Highly variable, infantile neurovisceral Niemann Pick disease (Type A ASMD) is usually fatal before 3 years of age. Estimasted mortality before adulthood for the Chronic visceral form (type B) is around 15-25%. Many live well into adulthood and may reach a normal lifespan. Diagnosis have been made in the 7th decade of life. |
| Fabry disease | α-galactosidase A | Glycolipids, particularly ceramide trihexoside, in brain, heart, kidney | Ischemic infarction in affected organs Acroparesthesia Angiokeratomas hypohidrosis | X-linked | Between 1 in 40,000 to 1 in 120,000 live births for males | Enzyme replacement therapy (but expensive) | Life expectancy among males of approximately 60 years |
| Krabbe disease | Galactocerebrosidase | Glycolipids, particularly galactocerebroside, in oligodendrocytes | Spasticity Neurodenegeration (leading to death) Hypertonia Hyperreflexia Decerebration-like posture Blindness Deafness | Autosomal recessive | About 1 in 100,000 births | Bone marrow transplant (high risk, potential failure, effectively provides enzyme replacement to the central nervous system from six months post-transplant, if done in the earliest stages; less effective enzyme replacement provision for the peripheral nervous system) | Untransplanted, and in the case of a failed transplant, generally fatal before age 2 for infants |
| Gaucher disease | Glucocerebrosidase | Glucocerebrosides in RBCs, liver and spleen | Hepatosplenomegaly Pancytopenia Bone pain Erlenmeyer flask deformity | Autosomal recessive | About 1 in 20,000 live births, more among Ashkenazi Jews | Enzyme replacement therapy (but expensive) | May live well into adulthood |
| Tay–Sachs disease | Hexosaminidase A | GM2 gangliosides in neurons | Neurodegeneration Developmental disability Early death | Autosomal recessive | Approximately 1 in 320,000 newborns in the general population, more in Ashkenazi Jews | None | Death by approx. 4 years for infantile Tay–Sachs |
| Metachromatic leukodystrophy (MLD) | Arylsulfatase A or prosaposin | Sulfatide compounds in neural tissue | Demyelination in CNS and PNS: Mental retardation Motor dysfunction Ataxia Hyporeflexia Seizures | Autosomal recessive | 1 in 40,000 to 1 in 160,000 | Bone marrow transplant (high risk, potential failure, effectively provides enzyme replacement to the central nervous system from six months post-transplant, if done in the earliest stages; less effective enzyme replacement provision for the peripheral nervous system) | Untransplanted, and in the case of a failed transplant, death by approx. 5 years for infantile MLD |