A 4-month-old boy is brought to the physician because of failure to thrive since birth. He is below the 5th percentile for length and at the 100th percentile for weight. Physical examination shows a doll-like face and marked hepatomegaly. After a 4-hour fast, serum studies show a decreased glucose concentration and increased concentrations of lactate, triglycerides, and uric acid. Which of the following is the most likely mechanism for the increased serum uric acid concentration in this patient?

Question

Quizplus · Accepted Answer

The increased serum uric acid concentration is due to increased degradation of hepatic purine nucleotides, which is a result of glycogen storage disease type I (Von Gierke disease). This condition leads to increased production of ribose-5-phosphate, which enhances purine synthesis and subsequent degradation to uric acid.  This patient most likely has a deficiency in the purine nucleotide salvage enzyme, hypoxanthineguanine phosphoribosyltransferase (HGPRT). The uric acid overproduction, and its associated consequences (eg, gouty arthritis), are likely the result of a block in purine nucleotide salvage, leading to increased catabolism to uric acid resulting in hyperuricemia.

A 4-Month-Old Boy Is Brought to the Physician Because of Failure