A 6-month-old boy is brought to the office by his mother out of concern that he is not developing normally. He has been feeding regularly and has had no medical problems other than a mild respiratory infection a month earlier. However, the mother says, "he doesn't seem to be as interactive as my other children were at his age." Physical examination reveals delayed developmental milestones and hypotonia. Two years later, the child is found to have involuntary movements and demonstrates a tendency to aggressively bite his own lips and fingers. Laboratory analysis shows an elevated blood uric acid level. Activity of which of the following enzymes is most likely increased as a result of this patient's condition?

Question

A 6-month-old boy is brought to the office by his mother out of concern that he is not developing normally.  He has been feeding regularly and has had no medical problems other than a mild respiratory infection a month earlier.  However, the mother says, "he doesn't seem to be as interactive as my other children were at his age."  Physical examination reveals delayed developmental milestones and hypotonia.  Two years later, the child is found to have involuntary movements and demonstrates a tendency to aggressively bite his own lips and fingers.  Laboratory analysis shows an elevated blood uric acid level.  Activity of which of the following enzymes is most likely increased as a result of this patient's condition?

Quizplus · Accepted Answer

11ec160b_36ee_2200_9249_6b827c4c62bf_MD0001_00 This patient has Lesch-Nyhan syndrome, an X-linked recessive disorder characterized by the development of dystonia, choreoathetosis, self-mutilation, and hyperuricemia within the first few years of life. The condition is caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), an enzyme that normally functions in the purine salvage pathway to convert hypoxanthine back to inosine monophosphate and guanine back into guanosine monophosphate. The absence of HGPRT results in increased degradation of guanine and hypoxanthine bases into uric acid, which increases the demand for de novo purine synthesis. The first step of purine synthesis is the formation of phosphoribosyl pyrophosphate (PRPP) by PRPP synthetase. PRPP can be used by adenine phosphoribosyltransferase and HGPRT for purine salvage, or it can be converted to phosphoribosylamine by PRPP amidotransferase in the first committed step of de novo purine synthesis. Because purine salvage is impaired in Lesch-Nyhan syndrome, the activity of PRPP amidotransferase must increase to supply a sufficient quantity of purine nucleotides. (Choices A, B, and F) These enzymes are involved in pyrimidine synthesis. Their activity would not be significantly altered in Lesch-Nyhan syndrome, which impairs purine salvage. (Choice C) The activity of HGPRT is decreased (not increased) in Lesch-Nyhan syndrome. (Choice E) Purine and pyrimidine nucleotides are initially synthesized as bases attached to a ribose sugar. The enzyme ribonucleotide reductase converts ribose sugars to their deoxyribose forms for use in DNA synthesis. This enzyme is negatively regulated by accumulation of deoxyribose nucleotides; its activity is determined primarily by the cellular proliferation rate (increased cell division requires more deoxyribose nucleotides). Educational objective: Lesch-Nyhan syndrome is an X-linked recessive disorder caused by a defect in hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This results in failure of the purine salvage pathway, leading to increased degradation of hypoxanthine and guanine to uric acid. De novo purine synthesis must increase to replace the lost bases, necessitating an increase in phosphoribosyl pyrophosphate (PRPP) amidotransferase activity.

A 6-Month-Old Boy Is Brought to the Office by His