LIPID STORAGE DISEASES

2. 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

3. Genetics
 All are inherited in autosomal recessive
mendelian fashion except for the X-
linked Fabry’s disease.

4. Inborn Errors of Lipid Metabolism: Lysosomal (or
Lipid) Storage Diseases.
Disease Enzyme Defect Accumulated Tissues Involved
Lipid
Tay–Sachs disease1 Hexosaminidase A GM2 Brain, retina
ganglioside
Gaucher's disease1 –Glucosidase Glucocerebros Liver, spleen, bone
(glucocerebrosidase) ide marrow, brain
Neimann–Pick Sphingomyelinase Sphingomyeli Brain, liver, spleen
disease1 n
Metachromatic Arylsulfatase A Sulfatide Brain, kidney, liver,
leukodystrophy peripheral nerves
Fabry's disease –Galactosidase Ceramide Skin, kidney
trihexoside
Krabbe's disease Galactosylceramidase Galactocerebr Brain
oside

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. Tay Sach disease: Inheritance
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. Niemann-Pick Disease

10. 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.

11. No cure for this disease.
Symptomatic treatment is
given.
Enzyme replacement
therapy and Gene therapy
are under trial.

12. Gaucher disease

13. 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

14. 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.

15.  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

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

17. Treatment
Enzyme replacement therapy(ERT)
by recombinant β- Glucocerebrosidase
is currently done.
 Surgical Care:
Partial and total Splenectomy was once advocated in the
treatment of patients with Gaucher disease.
 Bone marrow transplant is also helpful.
 Gene replacement is the permanent cure.

18. 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

19. 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

20. Niemann Pick disease :Clinical manifestation

21. 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

22. Gaucher’s Disease

23. The distended phagocytic cells,
known as Gaucher cells, are found
in the spleen, liver, bone marrow,
lymph nodes, tonsils, thymus, and
Peyer patches .

24.  The spleen in Gaucher disease.
 Typical Gaucher cells have foamy cytoplasm
and eccentrically located nuclei.

28. Fabry’s Disease
 X-linked recessive sphyngolipidosis
 α-galactosidase deficiency
 Ceramide trihexose in kidneys
 Renal failure, purpuric skin lesions, CNS
symptoms

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