Amino acid metabolism: tetrahydrobiopterin deficiency: practice question

A Biochemistry question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Biochemistry · Amino acid metabolism: tetrahydrobiopterin deficiency

Sample item

A 4-month-old infant has high blood phenylalanine and was started on a low phenylalanine diet, with phenylalanine falling to normal. However, the child has progressive hypotonia, seizures and developmental regression. Phenylalanine hydroxylase gene testing is normal. What best explains the continuing neurological decline?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

A. Deficient tetrahydrobiopterin impairs tyrosine and tryptophan hydroxylases, causing dopamine and serotonin deficiency

Tetrahydrobiopterin is the cofactor for phenylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydroxylase and nitric oxide synthase. Defects of its synthesis or regeneration (for example dihydropteridine reductase deficiency) raise phenylalanine and also cause dopamine and serotonin deficiency, which diet alone cannot correct. Diagnosis uses urinary pterins and dihydropteridine reductase activity, and treatment adds tetrahydrobiopterin with L-dopa-carbidopa and 5-hydroxytryptophan.

Option by option

  • A. Deficient tetrahydrobiopterin impairs tyrosine and tryptophan hydroxylases, causing dopamine and serotonin deficiency (correct)

    Correct. Cofactor deficiency also blocks catecholamine and serotonin synthesis, independent of the phenylalanine level.

  • B. Accumulation of homogentisic acid in the brain

    Homogentisic acid accumulates in alkaptonuria and does not cause infantile neurological regression.

  • C. A second defect of the urea cycle causes chronic hyperammonaemia

    A urea cycle defect is not implied by the findings and would not be related to the raised phenylalanine.

  • D. Excess tyrosine from the diet is toxic to neurons

    Tyrosine is normally low or low-normal here, and excess tyrosine is not the mechanism.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is A, Deficient tetrahydrobiopterin impairs tyrosine and tryptophan hydroxylases, causing dopamine and serotonin deficiency. Tetrahydrobiopterin is the cofactor for phenylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydroxylase and nitric oxide synthase.

Why is "Accumulation of homogentisic acid in the brain" not the answer?

Homogentisic acid accumulates in alkaptonuria and does not cause infantile neurological regression.

Why is "A second defect of the urea cycle causes chronic hyperammonaemia" not the answer?

A urea cycle defect is not implied by the findings and would not be related to the raised phenylalanine.

Why is "Excess tyrosine from the diet is toxic to neurons" not the answer?

Tyrosine is normally low or low-normal here, and excess tyrosine is not the mechanism.

What concept does this question test?

It tests Amino acid metabolism: tetrahydrobiopterin deficiency in Biochemistry. Defects of its synthesis or regeneration (for example dihydropteridine reductase deficiency) raise phenylalanine and also cause dopamine and serotonin deficiency, which diet alone cannot correct. Diagnosis uses urinary pterins and dihydropteridine reductase activity, and treatment adds tetrahydrobiopterin with L-dopa-carbidopa and 5-hydroxytryptophan.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Amino acid metabolism: tetrahydrobiopterin deficiency?

Build one table of enzyme deficiency, disease, inheritance and key finding, then revise it by spaced recall. Then use the flashcards and the other Biochemistry questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.