Amino acid metabolism: glycine cleavage system: 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: glycine cleavage system

Sample item

A 3-day-old neonate has hiccups, profound lethargy, hypotonia and myoclonic seizures, with a high CSF to plasma glycine ratio and normal blood ammonia and urine organic acids. Which defect is most likely?

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

The answer and the reasoning

C. Deficiency of the glycine cleavage enzyme system

Nonketotic hyperglycinaemia results from defective glycine cleavage system, a mitochondrial complex that degrades glycine to carbon dioxide, ammonia and a methylene group transferred to tetrahydrofolate. Glycine accumulates, especially in CSF, where it overstimulates NMDA receptors and acts at inhibitory glycine receptors, causing neonatal encephalopathy and seizures. Blood ammonia and organic acids are normal, in contrast with organic acidaemias and urea cycle defects.

Option by option

  • A. Deficiency of ornithine transcarbamylase

    Ornithine transcarbamylase deficiency causes marked hyperammonaemia with high urinary orotic acid.

  • B. Deficiency of branched-chain ketoacid dehydrogenase

    Branched-chain ketoacid dehydrogenase deficiency gives maple syrup odour with raised branched-chain amino acids.

  • C. Deficiency of the glycine cleavage enzyme system (correct)

    Correct. Failure to cleave glycine raises CSF glycine out of proportion to plasma.

  • D. Deficiency of propionyl-CoA carboxylase

    Propionyl-CoA carboxylase deficiency causes ketoacidosis with abnormal urine organic acids.

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 C, Deficiency of the glycine cleavage enzyme system. Nonketotic hyperglycinaemia results from defective glycine cleavage system, a mitochondrial complex that degrades glycine to carbon dioxide, ammonia and a methylene group transferred to tetrahydrofolate.

Why is "Deficiency of ornithine transcarbamylase" not the answer?

Ornithine transcarbamylase deficiency causes marked hyperammonaemia with high urinary orotic acid.

Why is "Deficiency of branched-chain ketoacid dehydrogenase" not the answer?

Branched-chain ketoacid dehydrogenase deficiency gives maple syrup odour with raised branched-chain amino acids.

Why is "Deficiency of propionyl-CoA carboxylase" not the answer?

Propionyl-CoA carboxylase deficiency causes ketoacidosis with abnormal urine organic acids.

What concept does this question test?

It tests Amino acid metabolism: glycine cleavage system in Biochemistry. Glycine accumulates, especially in CSF, where it overstimulates NMDA receptors and acts at inhibitory glycine receptors, causing neonatal encephalopathy and seizures. Blood ammonia and organic acids are normal, in contrast with organic acidaemias and urea cycle defects.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. 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: glycine cleavage system?

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.