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  1. 1. Introduction Lipid storage diseases (Lipidoses) are a group of diseases that arise from a deficiency of a specific lysosomal hydrolase with a resulting accumulation of the enzyme’s specific substrate. They are examples of lysosomal storage diseases. The substrates share the ceramide molecule. Clinical symptoms of these disorders are mainly from accumulation of the substrates in various body organ-systems
  2. 2. Genetics All are inherited in autosomal recessive mendelian fashion except for the X- linked Fabry’s disease.
  3. 3. Inborn Errors of Lipid Metabolism: Lysosomal (or Lipid) Storage Diseases.Disease Enzyme Defect Accumulated Tissues Involved LipidTay–Sachs disease1 Hexosaminidase A GM2 Brain, retina gangliosideGauchers disease1 –Glucosidase Glucocerebros Liver, spleen, bone (glucocerebrosidase) ide marrow, brainNeimann–Pick Sphingomyelinase Sphingomyeli Brain, liver, spleendisease1 nMetachromatic Arylsulfatase A Sulfatide Brain, kidney, liver,leukodystrophy peripheral nervesFabrys disease –Galactosidase Ceramide Skin, kidney trihexosideKrabbes disease Galactosylceramidase Galactocerebr Brain oside
  4. 4. Tay Sach Disease: Biomedical defect This is an inborn error of metabolismdue to failure of degradation ofgangliosides. The enzyme hexosaminidase A is deficient. composed of an α and β subunits Mutation in α subunit,15q23
  5. 5. Tay Sach disease: InheritanceIt is inherited as an autosomal recessivetraits, with a predilection in the AshkenaziJewish population, where the carrierfrequency is about 1/25.
  6. 6. Tay Sach Disease: Clinical Symptoms and classification Tay-Sachs disease is classified in variant forms, based on the time of onset of neurological symptoms. Infantile TSD  Birth: normal but develop  Loss of motor skills  Increased startle reaction  Macullar pallor and retinal cherry red spot  5-6 months  Decreased eye contact  Hyperacusis  Progressive development of idiocy and blindness  are diagnostic of this disease and they are due to wide spread injury to ganglion cells, in brain and retina.
  7. 7. Tay Sach Disease: Clinical symptoms and Classication Juvenile TSD extremely rare presents itself in children between 2 - 10 years develop cognitive, motor, speech difficulties (dysarthria), swallowing difficulties (dysphagia), unsteadiness of gait (ataxia), and spasticity. Patients with Juvenile TSD usually die between 5–15 years.
  8. 8. Niemann-Pick Disease
  9. 9. Diagnosis of Tay-Sach disease is usually suspected in an infant with neurologic features and a cherry-red spot. Enzymatic Assays-Definitive diagnosis is by determination of the level of ß- hexosaminidase A in isolated blood leukocytes. Fine needle Aspiration Cytology of brain tissue – can show the degree of neuronal degeneration. FNAC has a great potential for diagnosis and follow-up of Tay-Sachs disease Prenatal screening-Future at-risk pregnancies for both disorders can be monitored by prenatal diagnosis by amniocentesis or chorionic villus sampling.
  10. 10. No cure for this disease. Symptomatic treatment is given. Enzyme replacementtherapy and Gene therapy are under trial.
  11. 11. Gaucher disease
  12. 12. Gaucher disease :Biochemical defect results from deficient activity of Lysosomal Hydrolase, β- Glucocerebrosidase. enzyme defect results in accumulation of undegraded glycolipid in the form of Glucosyl ceramide in the cells of reticuloendothelial system.β-Glucocerebrosidase
  13. 13. There are three clinical subtypes 1)Type-1- (from early childhood- adulthood) easy bruising due to thrombocytopenia, chronic fatigue due to anemia, hepatomegaly Progressive enlargement of spleen Clinical bone involvement in the form of bone pains, or pathological fractures. 
  14. 14.  Enzyme activity testing:A finding of less than 15%of mean normal activity is diagnostic. Genotype testing:Molecular diagnosis can be helpful,Especially in Ashkenazi patients. Complete blood count: to assess the degree of cytopenia. Liver function enzyme testing:the presence of jaundice or impaired hepatocellular synthetic function
  15. 15. Ultrasonography Hip MRI may be useful in revealing early avascular necrosis.Skeletalradiography Liver biopsy
  16. 16. TreatmentEnzyme replacement therapy(ERT)by recombinant β- Glucocerebrosidaseis currently done. Surgical Care:Partial and total Splenectomy was once advocated in thetreatment of patients with Gaucher disease. Bone marrow transplant is also helpful. Gene replacement is the permanent cure.
  17. 17. Niemann Pick disease: clinical significance Occurs due to impaired degradation of shingomyelins. There is deficiency of sphingomyelinase enzyme. Due to non degradation, there is accumulation of shingomyelin in liver, spleen, bone marrow, and brain
  18. 18. Niemann Pick disease: Inheritance Isa congenital disease Autosomal recessive in nature There are 2 types: A and B Type A: more common present in 1/40000 population Type B: present in 1/80000 population More common in Jewish population
  19. 19. Niemann Pick disease :Clinical manifestation
  20. 20. Gaucher’s Disease A kind of lipid storage disease β-glucocerebrosidase deficiency Macrophage (wrinkled, striated) with lipid in lymph nodes, spleen, liver Type 2 (infantile) and type 3 (juvenile) have worse prognosis Type 1 (adult) can live longer Pseudo-Gaucher cell seen in CML with cholesterol from cell turn over
  21. 21. Gaucher’s Disease
  22. 22. The distended phagocytic cells,known as Gaucher cells, are found in the spleen, liver, bone marrow, lymph nodes, tonsils, thymus, and Peyer patches .
  23. 23.  The spleen in Gaucher disease. Typical Gaucher cells have foamy cytoplasm and eccentrically located nuclei.
  24. 24. Fabry’s Disease X-linked recessive sphyngolipidosis α-galactosidase deficiency Ceramide trihexose in kidneys Renal failure, purpuric skin lesions, CNS symptoms
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  26. 26. THANK YOU