Lipid storage diseases

Important lipid storage diseases

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

2. Lipid storage diseases Presented by; Shivanee Dunneram Roll no:18

3. Table of contents

4. any of a group of relatively rare hereditary disorders of fat metabolism, characterized by the accumulation of distinctive types of lipids; Gangliosides cerebrosides, or sphingomyelins, in various body structures. Each type of lipid accumulates as a result of a defect in one of the several organic catalysts or enzymes that normally metabolize it inside the cell. Introduction: lipid storage diseases or sphingolipidosis

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 Hexosaminidase A

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 T ay -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

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. Carrier screening - Identification of carriers within families is also possible by ß- hexosaminidase A and B determination.

11. Treatment of Tay-Sach disease 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. Gaucher disease: Clinical features 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. Gaucher disease: Clinical features 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 .

16. Gaucher disease: Laboratory Diagnosis 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

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

18. 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.

19. 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

20. 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

21. 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.

22.   Disease Enzyme Deficiency Lipid Accumulating Clinical Symptoms Tay Sach’s Disease Hexosaminidase A G M2 Ganglioside Mental retardation, blindness, muscular weakness Fabry's disease α- Galactosidase Globotriaosylceramide Skin rash, kidney failure (full symptoms only in males; X-linked recessive). Metachromatic leukodystrophy Arylsulfatase A Sulfogalactosylceramide Mental retardation and 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 Sphingomyelinase  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

23. References