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Biochemistry For Medicshttp://www.namrata.co/

Published in Students corner

By- Shivanee Dunneram

Lipid StorageDiseases

http://www.namrata.co/http://www.namrata.co/

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Presented by;ShivaneeDunneramRoll no:18

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Introduction

Tay Sach Disease

Gaucher Disease

Niemann Pick Disease

Other lipid storageDiseases

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Tay Sach Disease: Biomedical defect

This is an inborn error of metabolism

due to failure of degradation ofgangliosides.

The enzyme hexosaminidase A

is deficient.composed of an and subunits

Mutation in subunit,15q23

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It is inherited as an autosomal recessive traits, witha predilection in the Ashkenazi Jewish population,where the carrier frequency is about 1/25.

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Tay Sach Disease: Clinical Symptoms and classification

Tay-Sachs disease is classified in variant forms, based onthe 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.

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Tay Sach Disease: Clinical symptoms and

Classication

Juvenile TSD extremely rare

presents itself in children between 2 - 10 yearsdevelop cognitive,

motor, speech difficulties (dysarthria),

swallowing difficulties (dysphagia),

unsteadiness of gait (ataxia),

and spasticity.

Patients with Juvenile TSD usually

die between 515 years.

S h i Cli i l d

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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

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This disease is a multisystem lipidosis

characterized by hematological changes,organomegaly and skeletal involvement,

manifested in the form of bone pains andmultiple fractures.

It is the most common geneticdisorder among Ashkenazi Jews.

It is the commonest Lysosomal

storage disease.

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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 reticuloendothelialsystem.

-

Glucocerebrosidase

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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.

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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.

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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

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Hip MRI maybe useful inrevealing earlyavascularnecrosis.

Ultrasonography

Skeletal

radiography Liver biopsy

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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

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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 Enzyme Lipid Accumulating Clinical Symptoms

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Disease Enzyme

Deficiency

Lipid Accumulating Clinical Symptoms

Tay Sachs Disease Hexosaminidase

A

GM2 Ganglioside Mental retardation, blindness,

muscular weakness

Fabry's disease -Galactosidase Globotriaosylceramid

e

Skin rash, kidney failure (full

symptoms only in males; X-

linked recessive).

Metachromatic leukodystrophy Arylsulfatase A Sulfogalactosylceram

ide

Mental retardation and

Psychologic disturbances in

adults; demyelination.

Krabbe's disease -Galactosidase Galactosylceramide Mental retardation; myelin

almost absent.

Gaucher's disease -Glycosidase Glucosyl ceramide Enlarged liver and spleen,

erosion of long bones, mental

retardation in infants.

Niemann-Pick disease Sphingomyelina

se

Sphigomyelin Enlarged liver and spleen,

mental retardation; fatal in early

life.

Farber's disease Ceramidase Ceramide Hoarseness, dermatitis, skeletal

deformation, mental retardation;

fatal in early life

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Class

notes

Internet

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