Sunday, October 28, 2012

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.

DiseaseEnzyme DeficiencyLipid AccumulatingClinical Symptoms
Tay Sach’s DiseaseHexosaminidase AGM2 GangliosideMental retardation, blindness, muscular weakness
Fabry’s diseaseα-GalactosidaseGlobotriaosylceramideSkin rash, kidney failure (full symptoms only in males; X-linked recessive).
Metachromatic leukodystrophyArylsulfatase ASulfogalactosylceramideMental retardation and Psychologic disturbances in adults; demyelination.
Krabbe’s diseaseβ-GalactosidaseGalactosylceramideMental retardation; myelin almost absent.
Gaucher’s diseaseβ -GlycosidaseGlucosyl ceramideEnlarged liver and spleen, erosion of long bones, mental retardation in infants.
Niemann-Pick diseaseSphingomyelinase SphigomyelinEnlarged liver and spleen, mental retardation; fatal in early life.
Farber’s diseaseCeramidaseCeramideHoarseness, dermatitis, skeletal deformation, mental retardation; fatal in early life

------------------------------------------ Best Wishes: Dr.Ehab Aboueladab, Tel:01007834123, ------------------------------------------
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