Q.89 Tay–Sachs disease is a human genetic disorder that is associated with defects in which
ONE of the following cellular organelles?
(A) Endoplasmic reticulum (B) Mitochondria
(C) Golgi apparatus (D) Lysosome
Tay-Sachs disease results from defects in the lysosome. This autosomal recessive disorder arises due to mutations in the HEXA gene, leading to deficient β-hexosaminidase A enzyme activity. The enzyme normally degrades GM2 gangliosides in lysosomes, and its absence causes lipid accumulation, primarily in neurons.
Option Analysis
Tay-Sachs is classified as a lysosomal storage disease, where the primary defect lies in lysosomal function.
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(A) Endoplasmic reticulum: The HEXA gene product (α-subunit of hexosaminidase A) is synthesized in the ER, and some mutations cause misfolding leading to ER-associated degradation (ERAD). However, the disease manifests from failed lysosomal degradation, not primary ER dysfunction.
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(B) Mitochondria: Secondary mitochondrial dysfunction, such as impaired respiration or oxidative stress, occurs due to lysosomal storage impacts but is not the causal organelle defect.
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(C) Golgi apparatus: The enzyme gains mannose-6-phosphate tags in the Golgi for lysosomal targeting, but defects here are not the primary cause of Tay-Sachs.
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(D) Lysosome: Correct. β-hexosaminidase A resides in lysosomes to break down GM2 gangliosides; deficiency leads to their toxic buildup, neuronal death, and symptoms like cherry-red spot and neurodegeneration.
Tay-Sachs disease lysosome defect defines this fatal lysosomal storage disorder, where deficient hexosaminidase A enzyme fails to degrade GM2 gangliosides in neurons. Common in certain populations like Ashkenazi Jews, it leads to progressive neurodegeneration starting in infancy.
Causes and Pathophysiology
Mutations in the HEXA gene on chromosome 15 impair the α-subunit, preventing enzyme function in lysosomes. Undigested lipids swell neurons, causing seizures, blindness (cherry-red spot), and death by age 4. Unlike other options, the lysosome is the site of accumulation, confirming it as the defective organelle.
Symptoms and Diagnosis
Infants show developmental delay, exaggerated startle, hypotonia turning to spasticity. Diagnosis via low hexosaminidase A in leukocytes or genetic testing; carrier screening prevents inheritance.
Exam Relevance for CSIR NET
Questions test lysosomal role in storage diseases. Differentiate: ER for synthesis (not primary), mitochondria/Golgi secondary. Focus: Tay-Sachs disease lysosome defect as key fact.
