A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 9-month-old infant presents to your office for a check-up. Exam reveals mental retardation, microcephaly, and a mousy odor to his breath. You should be concerned that the infant may have which of the following?
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A
Deficit of phenylalanine hydroxylase activityCorrect. deficient phenylalanine hydroxylase causes phenylalanine accumulation, producing the mousy odor, intellectual disability, and microcephaly of classic PKU.
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B
Deficit of tyrosine hydroxylase activityIncorrect. tyrosine hydroxylase deficiency causes a dopamine deficiency syndrome with dystonia and parkinsonism, not the mousy odor or this phenotype.
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C
Excess tetrahydrobiopterin cofactorIncorrect. excess BH4 would not cause disease; it is the cofactor for PAH, and BH4 deficiency (not excess) causes a malignant PKU variant.
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D
Excess phenylalanine hydroxylase activityIncorrect. excess PAH activity is not a recognized disease and would only deplete phenylalanine, not produce intellectual disability.
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E
Deficit of homogentisate oxidase activityIncorrect. Homogentisate oxidase deficiency causes alkaptonuria—black urine on standing, ochronosis, and arthritis later in life—not the mousy odor, microcephaly, and intellectual disability of phenylketonuria.
↑ Tap an answer to reveal the reasoning
Answer: A. Mental retardation, microcephaly, and a characteristic mousy or musty body odor in an infant are pathognomonic for phenylketonuria (PKU). PKU is an autosomal recessive deficiency of phenylalanine hydroxylase (PAH), the enzyme that converts phenylalanine to tyrosine using tetrahydrobiopterin (BH4) as a cofactor.
Without functional PAH, phenylalanine and its breakdown products (phenylacetate, phenyllactate, phenylpyruvate) accumulate; the latter give the urine and breath their musty odor. High phenylalanine is neurotoxic, producing the cognitive and developmental impairment, and the resulting lack of tyrosine causes hypopigmentation of skin, hair, and eyes. PKU is screened on the newborn heel-prick precisely because early dietary intervention prevents disability.
Treatment is a low-phenylalanine diet (avoid aspartame, milk, meats high in phenylalanine) supplemented with tyrosine, which becomes a conditionally essential amino acid. BH4-responsive variants exist and can be treated with sapropterin.
**Why each option:**
**A.** Correct — deficient phenylalanine hydroxylase causes phenylalanine accumulation, producing the mousy odor, intellectual disability, and microcephaly of classic PKU.
**B.** Incorrect — tyrosine hydroxylase deficiency causes a dopamine deficiency syndrome with dystonia and parkinsonism, not the mousy odor or this phenotype.
**C.** Incorrect — excess BH4 would not cause disease; it is the cofactor for PAH, and BH4 deficiency (not excess) causes a malignant PKU variant.
**D.** Incorrect — excess PAH activity is not a recognized disease and would only deplete phenylalanine, not produce intellectual disability.