Important lipid storage diseases

1. Lipid Storage
Diseases
Published in Students corner
Biochemistry For Medics
http://www.namrata.co/
By- Shivanee Dunneram

2. Presented by;
Shivanee
Dunneram
Roll no:18

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

5. 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 α and β subunits
 Mutation in α subunit,15q23

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

7. 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.

8. 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.

9. 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

13. 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.

14. 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

15. 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.

16. 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.

17. • 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

18. Ultrasonography
Hip MRI may
be useful in
revealing early
avascular
necrosis.
Skeletal
radiography Liver biopsy

21. 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

22. 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.

23. Disease Enzyme Lipid Accumulating Clinical Symptoms
Deficiency
Tay Sach’s Disease Hexosaminidase GM2 Ganglioside Mental retardation, blindness,
A muscular weakness
Fabry's 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.
Krabbe's disease β-Galactosidase Galactosylceramide Mental retardation; myelin
almost absent.
Gaucher's 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.
Farber's disease Ceramidase Ceramide Hoarseness, dermatitis, skeletal
deformation, mental retardation;
fatal in early life

25. Class
notes
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