Lipid Storage Diseases

Published in Students corner Biochemistry For Medics http://www.namrata.co/

By- Shivanee Dunneram

Presented by; Shivanee Dunneram Roll no:18

Introduction Tay Sach Disease Gaucher Disease Niemann Pick Disease Other lipid storage Diseases

Tay Sach Disease: Biomedical defect

This is an inborn error of metabolism due to failure of degradation of gangliosides. The enzyme hexosaminidase A is deficient. composed of an and subunits Mutation in subunit,15q23

It is inherited as an autosomal recessive traits, with a predilection in the Ashkenazi Jewish population, where the carrier frequency 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 515 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 skeletal involvement, manifested in the form of bone pains and multiple fractures.

It is the most common genetic disorder among Ashkenazi Jews.

It is the commonest Lysosomal storage disease.

Gaucher disease :Biochemical defect

results from deficient activity of Lysosomal Hydrolase, - Glucocerebrosidase. enzyme defect results in accumulation of undegraded glycolipid in the form of Glucosyl ceramide in the cells of reticuloendothelial system.

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

Ultrasonography

Hip MRI may be useful in revealing early avascular necrosis.

Skeletal radiography

Liver biopsy

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 manifestation

TypeA Niemann Pick disease: there is progressive mental retardation, hepatosplenomegaly because of progressive accumulation of sphingomyelin Children die within 2 years of life Type 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 Tay Sachs Disease Fabry's disease

Enzyme Deficiency

Lipid Accumulating

Clinical Symptoms Mental retardation, blindness, muscular weakness

Hexosaminidase GM2 Ganglioside A

-Galactosidase Globotriaosylceramid Skin rash, kidney failure (full e symptoms only in males; Xlinked recessive). Arylsulfatase A Sulfogalactosylceram Mental retardation and ide Psychologic disturbances in adults; demyelination. Mental retardation; myelin almost absent. Enlarged liver and spleen, erosion of long bones, mental retardation in infants. Enlarged liver and spleen, mental retardation; fatal in early life. Hoarseness, dermatitis, skeletal deformation, mental retardation; fatal in early life

Metachromatic leukodystrophy

Krabbe's disease Gaucher's disease

-Galactosidase Galactosylceramide -Glycosidase Glucosyl ceramide

Niemann-Pick disease

Sphingomyelina se Ceramidase

Sphigomyelin

Farber's disease

Ceramide

Class notes

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