Q.17 Niemann-Pick disease is caused due to a genetic deficiency of
- β-Galactosidase
- Ceramidase
- Sphingomyelinase
- α-Galactosidase
Niemann-Pick disease types A and B are caused by a genetic deficiency of sphingomyelinase. This lysosomal storage disorder leads to sphingomyelin buildup in cells, particularly macrophages.
Correct Answer
Sphingomyelinase
Option Analysis
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β-Galactosidase: Incorrect. Deficiency causes GM1 gangliosidosis or Morquio B syndrome, leading to ganglioside or keratan sulfate accumulation.
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Ceramidase: Incorrect. Deficiency results in Farber disease, with ceramide buildup causing joint pain, nodules, and granulomas.
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Sphingomyelinase: Correct. Acid sphingomyelinase deficiency (from SMPD1 gene mutations) prevents sphingomyelin breakdown, causing hepatosplenomegaly, lung issues, and neurodegeneration in types A/B.
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α-Galactosidase: Incorrect. Deficiency causes Fabry disease, accumulating globotriaosylceramide and leading to kidney, heart, and pain issues.
Niemann-Pick disease sphingomyelinase deficiency is a rare genetic lysosomal storage disorder affecting lipid metabolism. Caused by mutations in the SMPD1 gene, it impairs acid sphingomyelinase, leading to sphingomyelin accumulation in organs like the liver, spleen, lungs, and brain.
Causes and Genetics
Niemann-Pick disease sphingomyelinase deficiency (types A and B) stems from deficient acid sphingomyelinase activity. This autosomal recessive condition arises from over 180 SMPD1 mutations on chromosome 11, blocking sphingomyelin hydrolysis to ceramide. Type C differs, involving NPC1/NPC2 genes and lipid transport issues, not sphingomyelinase.
Symptoms by Type
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Type A (Severe, Infantile): Failure to thrive, hepatosplenomegaly, cherry-red eye spot, neurodegeneration; fatal by age 3.
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Type B (Non-Neuronopathic): Milder; splenomegaly, lung disease, low platelets; longer survival.
Foam cells in bone marrow confirm diagnosis via enzyme assay or genetic testing.
Diagnosis and Treatment
Enzyme activity testing in leukocytes/fibroblasts diagnoses Niemann-Pick disease sphingomyelinase deficiency. No cure exists; supportive care includes enzyme replacement trials and symptom management. Early detection improves outcomes in type B.
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