Lipid Storage Disorders/Sphingolipidoses/ Lysosomal Storage Disorders - EASY NOTES

--Normal catabolism of sphingolipids is by series of lysosomal hydrolases enzymes like

1.α and β glucosidase, 

2.Galactosidase, 

3.Neuraminidase, 

4.Hexosaminidase &

5.Arylsulfatase

--Deficiency of a single enzyme results in failure of breakdown of sphingolipids thus causing these lipid storage disorders.

--Affected children are severely mentally retarded (MR)

--Pre-natal diagnosis of these disorders is by amniocentesis and by culture of amniotic fluids.

COMMON FEATURES OF ALL DISORDERS:

--Accumulation of only one type of sphingolipid

--Normal rate of synthesis of lipid but abnormal degradation of lipids

-- same extent of enzyme defect in all tissues

TYPES OF LIPID STORAGE DISORDERS

1.Niemann Pick's Disease

-AR(autosomal recessive)

-Enzyme Defect - Sphingomyelinase

-Lipid accumulated - Sphingomyelin

-Clinical Features - Severe CNS damage, hepatosplenomegaly, cherry rod spot in the macula

Death by 2 years of age

2.Gaucher's Disease

AR(autosomal recessive)

-Enzyme Defect - β - glucosidase

-Lipid accumulated - glucocerebroside

-Clinical Features - Hepatosplenomegaly, bone pain due to replacement of marrow cells by histiocytes loaded with lipids, replacement of marrow cells also leads to anemia, thrombocytopenia & leucopenia

3 types - Adult type, Infantile type, Juvenile type

3.Tay Sach's Disease

AR(autosomal recessive)

-Enzyme Defect - Hexosaminidase A

-Lipid accumulated - GM 2 ganglioside

-Clinical Features - wide spread injury to ganglion cells in the brain results in development of blindness in infant, cherry red spot in macula

-Death by 3-4 years of age

4.Metachromatic Leukodystrophy

-Enzyme Defect -  Aryl sulfatase

-Lipid accumulated - sulfogalactocerebroside

-Clinical Features - weakness, ataxia, hypotonia, paralysis, speech difficulty, optic atrophy.

2 types - Late infantile type, Adult type

5.Fabry's Disease

X linked dominant

-Enzyme Defect - α - galactosidase

-Lipid accumulated - ceramide trihexoside

-Clinical Features - reddish purple skin, accumulation of lipid in endothelial lining leading to vascular thrombosis, accumulation of lipids in glomeruli leading to renal failure, corneal opacity, cataract, vascular dilatation

-Death by 5 years of age

6.Krabbe's Leukodystrophy

Enzyme Defect - β - galactosidase

-Lipid accumulated - galactocerebroside

-Clinical Features - total absence of myelin in CNS leads to sever MR

7.Generalized Gangliosidoses

-Autosomal Recessive

Enzyme Defect - β - galactosidase

-Lipid accumulated - GM1 ganglioside, glycoprotein, keratin sulfate

8.Lactosyl Ceramidoses

Enzyme Defect - β-galactosidase

-Lipid accumulated - lactosyl ceramide

-Clinical Features - CNS and reticuloendothelial system are affected

9.Sandhoff's Disease

Enzyme Defect - hexosaminidase A & B

-Lipid accumulated - Globoside

-Clinical Features - Neurological deficit & mental retardation