Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Sphingolipidoses

319 views

Published on

sphingolipidoses for under graduate medical students

Published in: Education
  • Be the first to comment

  • Be the first to like this

Sphingolipidoses

  1. 1. Sphingolipidoses Dr.S.Sethupathy, M.D.,Ph.D., Department of Biochemistry, Rajah Muthiah Medical College, Annamalai University
  2. 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.
  3. 3. Globoside
  4. 4. PAPS synthase
  5. 5. 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.
  6. 6. 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.
  7. 7. Cherry red spot
  8. 8. 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.
  9. 9. D.Blue –GLU, L.Blue- sialic acid, W-NAcGal, Y- Gal
  10. 10. 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.
  11. 11. 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.
  12. 12. 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

×