Overview of sphingolipidosis (Lipid storage Diseases)

he sphingolipidosis (lipid storage diseases) are a group of inherited diseases that are caused by a genetic defect in the catabolism of lipids containing sphingosine. They are part of a larger group of lysosomal disorders and exhibit several constant features:

(1) Complex lipids containing ceramide accumulate in cells, particularly neurons, causing neuro degeneration and shortening the life span.

(2) The rate of synthesis of the stored lipid is normal.

(3) The enzymatic defect is in the lysosomal degradation pathway of sphingolipids.

(4) The extent to which the activity of the affected enzyme is decreased is similar in all tissues.

There is no effective treatment for many of the diseases, although some success has been achieved with enzyme replacement therapy and bone marrow transplantation in the treatment of Gaucher’s and Fabry’s diseases. Other promising approaches are substrate deprivation therapy to inhibit the synthesis of sphingolipids and chemical chaperone therapy. Gene therapy for lysosomal disorders is also currently under investigation.

Disease	Enzyme Deficiency	Lipid Accumulating	Clinical Symptoms
Tay Sach’s Disease	Hexosaminidase A	GM2 Ganglioside	Mental retardation, blindness, muscular weakness
Fabry’s disease	α-Galactosidase	Globotriaosylceramide	Skin rash, kidney failure (full symptoms only in males; X-linked recessive).
Metachromatic leukodystrophy	Arylsulfatase A	Sulfogalactosylceramide	Mental retardation and Psychologic disturbances in adults; demyelination.
Krabbe’s disease	β-Galactosidase	Galactosylceramide	Mental retardation; myelin almost absent.
Gaucher’s disease	β -Glycosidase	Glucosyl ceramide	Enlarged liver and spleen, erosion of long bones, mental retardation in infants.
Niemann-Pick disease	Sphingomyelinase	Sphigomyelin	Enlarged liver and spleen, mental retardation; fatal in early life.
Farber’s disease	Ceramidase	Ceramide	Hoarseness, dermatitis, skeletal deformation, mental retardation; fatal in early life

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