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
Genetics All are inherited in autosomal recessive mendelian fashion except for the X- linked Fabry’s disease.
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
Tay Sach disease: InheritanceIt is inherited as an autosomal recessivetraits, with a predilection in the AshkenaziJewish population, where the carrierfrequency is about 1/25.
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.
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.
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.
No cure for this disease. Symptomatic treatment is given. Enzyme replacementtherapy and Gene therapy are under trial.
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
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.
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
Ultrasonography Hip MRI may be useful in revealing early avascular necrosis.Skeletalradiography Liver biopsy
TreatmentEnzyme 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.
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
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
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