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    Subjects/Pediatrics/Common Single-Gene Disorders
    Common Single-Gene Disorders
    easy
    smile Pediatrics

    Which enzyme deficiency causes maple syrup urine disease (MSUD)?

    A. Propionyl-CoA carboxylase
    B. Branched-chain α-ketoacid dehydrogenase complex
    C. Homogentisate 1,2-dioxygenase
    D. Phenylalanine hydroxylase

    Explanation

    ## Maple Syrup Urine Disease (MSUD) ### Enzyme Deficiency **Key Point:** MSUD results from deficiency of the **branched-chain α-ketoacid dehydrogenase complex (BCKDC)**, which catalyzes the oxidative decarboxylation of branched-chain amino acids (leucine, isoleucine, valine). ### Biochemical Consequence When BCKDC is deficient: 1. Branched-chain amino acids (BCAAs) accumulate in blood and urine 2. Their corresponding α-ketoacids accumulate 3. These metabolites impart a characteristic **maple syrup odor** to urine and sweat ### Clinical Presentation - Onset: typically 4–7 days of life (classic form) - Symptoms: poor feeding, lethargy, hypotonia, seizures - Neurological damage results from toxic accumulation of BCAAs and their metabolites **High-Yield:** MSUD is an **autosomal recessive** disorder and is screened in newborn screening programs in many countries including India. ### Inheritance Pattern - **Autosomal recessive** — both parents are carriers - Affects approximately 1 in 185,000 live births globally **Clinical Pearl:** Early diagnosis via newborn screening and immediate dietary restriction of BCAAs can prevent severe neurological damage.

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