Functional and metabolic studies of platelets from patients with Lesch-Nyhan syndrome.
Platelet function was investigated in three patients with the Lesch-Nyhan syndrome. Platelet count, morphology and size distribution was normal in all patients. Platelet turnover was normal. Electron microscopy did not reveal any ultrastructural abnormality. Template bleeding times were normal and prolonged after aspirin ingestion in two out of the three patients: the patient that failed to respond to the aspirin challenge also had decreased retention of platelets on a glass bead column. Biochemical studies revealed that total platelet ATP was reduced by 34% in the presence of a normal level of ADP in the storage pool. These platelets failed to incorporate radioactive hypoxanthine but did incorporate radioactive adenine to produce adenine nucleotides and a trace amount of guanine nucleotides. The results indicate that normal platelets have a functionally intact pathway for utilizing hypoxanthine as a source of preformed purine, and that the failure to salvage this purine, as in the Lesch-Nyhan syndrome, results in a decreased level of total platelet ATP. These findings suggest that platelets can function normally despite a one third reduction in total ATP content.
D000228:Adenine Phosphoribosyltransferase / Q000097:blood; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000293:Adolescent; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002648:Child; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000097:blood; D007926:Lesch-Nyhan Syndrome / Q000201:enzymology / Q000378:metabolism*; D008297:Male
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000228:Adenine Phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase