sphingolipidoses for under graduate medical students

1. Sphingolipidoses
Dr.S.Sethupathy, M.D.,Ph.D.,
Department of Biochemistry,
Rajah Muthiah Medical College,
Annamalai University

2. 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.

5. Globoside

6. PAPS synthase

7. Lysosomal storage diseases
The lysosomal storage diseases are
a rare class of neurometabolic
disorders.
Metabolites of complex lipids
accumulate within neurons.
Mostly autosomal recessive fashion
For genetic counseling and for
monitoring future pregnancies.

8. 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.

9. Cherry red spot

13. 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.

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

15. 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.

20. 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.

21. 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