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
It is inherited as an autosomal recessive traits, witha predilection in the Ashkenazi Jewishpopulation, where the carrier frequency is about1/25.
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.
Tay Sach Disease: Clinical symptoms and Classication Adult/Late Onset TSD. rare form of the disorder occurs in patients in their 20s and early 30s.It is characterized by unsteadiness of gait and progressive neurological deterioration.Symptoms of LOTS, include speech and swallowing difficulties, unsteadiness of gait, spasticity, cognitive decline, and psychiatric illness
This disease is a multisystem lipidosis characterized by hematological changes, organomegaly and skeletalinvolvement, manifested in the form of bone pains and multiple fractures. It is the most common geneticdisorder among Ashkenazi Jews.It is the commonest Lysosomal storage disease.
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.
Type 2-• less common,• characterized by neurodegeneration, extreme visceral involvement• death within 2 years of life. Type 3-• is intermediate in presentation to type 1 and 2.• Neurological involvement is there but occurs later in life with decreased severity as compared to Type 2.
• 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
Niemann Pick disease: Inheritance• Is a 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
Niemann Pick disease :Clinical manifestationTypeA Niemann Pick disease: there is progressive mental retardation, hepatosplenomegaly because of progressive accumulation of sphingomyelin• Children die within 2 years of lifeType B: there is no involvement of brain but sphingomyelin is present in excessive amount in liver, spleen, and bone marrow.• Death occurs within 20 years of life• Treatment: only symptomatic• treatment is given.
Disease Enzyme Lipid Accumulating Clinical Symptoms DeficiencyTay Sach’s Disease Hexosaminidase GM2 Ganglioside Mental retardation, blindness, A muscular weaknessFabrys disease α-Galactosidase Globotriaosylceramid Skin rash, kidney failure (full e symptoms only in males; X- linked recessive).Metachromatic leukodystrophy Arylsulfatase A Sulfogalactosylceram Mental retardation and ide Psychologic disturbances in adults; demyelination.Krabbes disease β-Galactosidase Galactosylceramide Mental retardation; myelin almost absent.Gauchers disease β -Glycosidase Glucosyl ceramide Enlarged liver and spleen, erosion of long bones, mental retardation in infants.Niemann-Pick disease Sphingomyelina Sphigomyelin Enlarged liver and spleen, se mental retardation; fatal in early life.Farbers disease Ceramidase Ceramide Hoarseness, dermatitis, skeletal deformation, mental retardation; fatal in early life