Question 40:
A mutation in the GLA (alpha-galactosidase A) gene leads to which one of the following conditions?
A mutation in the GLA (alpha-galactosidase A) gene causes Fabry disease, making option (A) correct.
Question Solution
The GLA gene on the X chromosome encodes alpha-galactosidase A, a lysosomal enzyme that breaks down globotriaosylceramide (Gb3). Mutations reduce enzyme activity, leading to Gb3 accumulation in cells (especially kidneys, heart, nerves), causing Fabry disease symptoms like pain, angiokeratomas, and organ failure.
Option Analysis
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(A) Fabry disease: Correct; X-linked lysosomal storage disorder from GLA mutations impairing Gb3 degradation.
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(B) Gaucher disease: Incorrect; due to GBA gene mutations causing glucocerebroside buildup (beta-glucocerebrosidase deficiency).
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(C) Phenylketonuria: Incorrect; autosomal recessive from PAH gene mutations, blocking phenylalanine hydroxylation.
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(D) Cri-du-chat syndrome: Incorrect; deletion in 5p chromosome arm, not a single-gene enzyme defect (causes cat-like cry, intellectual disability).
A mutation in the GLA gene leads to Fabry disease, an X-linked lysosomal disorder key for GATE Life Sciences genetics questions. Over 900 GLA variants cause deficient alpha-galactosidase A, Gb3 buildup, and multi-organ damage.
Disease Breakdown
Fabry: GLA mutation → no Gb3 breakdown → vascular/renal issues (males severe; females milder). Gaucher: GBA defect → spleen/liver enlargement. PKU: PAH issue → mental retardation if untreated. Cri-du-chat: 5p deletion → developmental delays.
| Condition | Gene/Change | Key Defect |
|---|---|---|
| Fabry | GLA mutation | α-galactosidase A lack |
| Gaucher | GBA mutation | β-glucocerebrosidase lack |
| PKU | PAH mutation | Phenylalanine hydroxylase |
| Cri-du-chat | 5p deletion | Multiple genes lost |
Exam Tips
GATE focus: Lysosomal storage = Fabry (GLA); match enzyme to disease. Mnemonic: “GLA = Fabry’s Alpha woe.”
