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LIPID STORAGE DISEASES MUHAMMAD MUSTANSAR FJMC LAHORE
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LIPID STORAGE DISEASES MUHAMMAD MUSTANSAR FJMC LAHORE

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LIPID STORAGE DISEASES

LIPID STORAGE DISEASES

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  • 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. Genetics All are inherited in autosomal recessive mendelian fashion except for the X- linked Fabry’s disease.
  • 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. 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. 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. 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. 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. Niemann-Pick Disease
  • 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. No cure for this disease. Symptomatic treatment is given. Enzyme replacementtherapy and Gene therapy are under trial.
  • 11. Gaucher disease
  • 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. 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.  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. Ultrasonography Hip MRI may be useful in revealing early avascular necrosis.Skeletalradiography Liver biopsy
  • 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. 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. 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. Niemann Pick disease :Clinical manifestation
  • 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. Gaucher’s Disease
  • 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.  The spleen in Gaucher disease. Typical Gaucher cells have foamy cytoplasm and eccentrically located nuclei.
  • 24. Fabry’s Disease X-linked recessive sphyngolipidosis α-galactosidase deficiency Ceramide trihexose in kidneys Renal failure, purpuric skin lesions, CNS symptoms
  • 25.  
  • 26. THANK YOU

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