A 4-year-old boy is brought to the pediatrician by his mother because of a concern that he has been exhibiting self-injurious behavior. She states that for the past several weeks, he has been chewing on his lips and biting his fingers. They have attempted to redirect his behavior without success. He also has been complaining of pain in both knees and both ankles. Past medical history is significant for speech delay.
Deficiency of which of the following enzymes is most likely responsible for the patient's condition?
- A) Alpha-glucosidase
- B) Galactose-1-phosphate uridyltransferase
- C) Hypoxanthine-guanine phosphoribosyltransferase
- D) Muscle glycogen phosphorylase
C) Hypoxanthine-guanine phosphoribosyltransferase
Lesch-Nyhan syndrome is a congenital deficiency of the HGPRT enzyme. Lesch-Nyhan syndrome is an X-linked recessive disorder, so it presents in young boys. Affected individuals are unable to salvage guanine or hypoxanthine using the purine salvage pathway, and this leads to increased PRPP and an increase in de novo purine synthesis. This then leads to increased purine turnover and hyperuricemia. Patients with Lesch-Nyhan syndrome present at an early age with neurologic features of self-mutilation, spasticity, and cognitive defects. Orange uric acid crystals can be found in their diapers. Although there is no cure, treatment with allopurinol can decrease the hyperuricemia, but it does not alter the neurologic symptoms.
Answer choice A: Alpha-glucosidase, is incorrect. Alpha-glucosidase deficiency results in Pompe syndrome which presents with feeding problems, poor weight gain, muscle weakness, floppiness, and head lag in the first months of life.
Answer choice B: Galacose-1-phosphate uridyltransferase, is incorrect. Deficiency of galacose-1-phosphate uridyltransferase causes galactosemia in which an infant is unable to metabolize galactose and must be placed on a galactose-free diet. Galactosemia may present with severe and persistent jaundice, vomiting, diarrhea, electrolyte imbalances, and weight loss.
Answer choice D: Muscle glycogen phosphorylase, is incorrect. Muscle glycogen phosphorylase causes McArdle disease, a rare muscle disorder in which glycogen cannot be broken down. Presenting symptoms include fatigue, muscle pain, and muscle cramps within the first few minutes of exercise.
Key Learning Point
Lesch-Nyhan syndrome results from a congenital deficiency of Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and results in neurologic issues including self-mutilation, spasticity, and cognitive defects.