Sphingolipidoses

Dr.S.Sethupathy, M.D.,Ph.D.,

Department of Biochemistry,

Rajah Muthiah Medical College,

Annamalai University

Sphingolipids

The sphingolipids a complex range of lipids in which fatty acids are linked via amide bonds to a long-chain base or sphingoid.

They are also found in a few bacterial genera -Sphingomonas and Sphingobacterium.

Globoside

PAPS synthase

Lysosomal storage diseases

The lysosomal storage diseases are a rare class of neurometabolicdisorders.

Metabolites of complex lipids accumulate within neurons.

Mostly autosomal recessive fashion

For genetic counseling and for monitoring future pregnancies.

Sphingolipidoses

They are characterized by a progressive degenerative disease of the nervous system, with blindness, dementia, epilepsy, ataxia, paralysis, and hyperreflexia.

A cherry-red spot at the macula and optic atrophy are the most common signs

Ophthalmologic examination - an important clue to the diagnosis.

Cherry red spot

Gangliosides

Gangliosides are important constituents of gray matter.

They are glycosphingolipids that contain sialic acid in the oligosaccharide chain.

The metabolism of ganglioside involves the removal of the terminal galactose to convert GM1-ganglioside to GM2-ganglioside.

GM2-ganglioside is then hydrolyzed to GM3-ganglioside by the removal of N-acetylgalactosamine.

D.Blue –GLU, L.Blue- sialic acid,W-NAcGal, Y- Gal

Gangliosidoses

They are neuronal lipid storage disorders due to deficiencies of certain lysosomal hydrolases.

Autosomal recessive inheritance

Progressive mental and motor deterioration

Due to the storage of GM1- or GM2-ganglioside in neurons.

Prognosis

Lysosomal storage diseases are ultimately fatal

There is no effective treatment.

Almost all the disorders diagnosed by enzyme analysis.

Leukocytes and cultured skin fibroblasts or serum can be assayed for enzyme activity

Prenatal diagnosis is also possible.

Disease Enzyme Diagnostic Sample(s)

GM2-gangliosidosis

Tay-Sachs disease Hex A deficient Leukocyte serum

Sandhoff's disease Hex A and B deficient Leukocyte serum

AB variant Hex A, B normal GM2loading studies in

fibroblasts

B1variant Hex A deficient with sulfated

substrate

Leukocyte fibroblasts

Juvenile GM2-

gangliosidosis

Partial Hex A deficiency Leukocyte serum

Infantile GM1-

gangliosidosis

ß-Galactosidase deficient Leukocyte fibroblasts

Niemann-Pick disease

Type A, infantile Sphingomyelinase deficient Leukocyte fibroblasts

Type B Sphingomyelinase deficient Leukocyte fibroblasts

Farber's

lipogranulomatosis

Ceramidase Leukocyte fibroblasts

Sialidoses

Type 1 Sialidase deficient Fresh fibroblasts

Type 2 Sialidase and ß-galactosidase

deficient

Fresh fibroblasts