An 8-month-old child is brought to a pediatrician because of the mother's concern about the boy's tendency to compulsively bite his fingers. On questioning, the mother repoed that she has noticed yellow-orange crystals in his diapers, but has not mentioned them to anyone. A genetic defect in which of the following pathways should be suspected?
The condition is Lesch-Nyhan syndrome, and the yellow-orange crystals of uric acid in the diaper are an impoant, but often neglected, clue to early diagnosis. Lesch-Nyhan syndrome is characterized by a tremendous overproduction of purines, because the reutilization of purines the purine salvage pathway is blocked by a near total absence of hypoxanthine-guanine phosphoribosyl-transferase (HGP) activity. Patients with this severe X-linked disease, for reasons that are unknown, show aggressive behavior that leads to self-mutilation. They may also develop gouty ahritis or gouty nephropathy. Phenylketonuria is an example of a disorder of aromatic amino acid metabolism characterized by mental retardation. Maple syrup urine disease is an example of a disorder of branched chain amino acids causing motor abnormalities and seizures. Orotic aciduria is an example of a disorder of pyrimidine metabolism, characterized by retarded growth and development as well as megaloblastic anemia.
Aromatic amino acid metabolism
Branched chain amino acid metabolism
Purine metabolism
Pyrimidine metabolism