When and how does one search for inborn errors of purine and pyrimidine metabolism?

Abstract

Disorders in purine and pyrimidine metabolism may be difficult to recognize because their recent description means many arc little known. They cover a broad spectrum of illnesses, can present from birth to the 80s, have multiple symptoms and lead to early death. Recognition of new disorders requires skill and serendipity. Often parents of affected children provide valuable clues. These disorders should be suspected, particularly where the history involves siblings, in anaemia, susceptibility to infection, or neurological deficits including autism, delayed development, epilepsy, self-mutilation, muscle weakness and — unusual in children and adolescents — gout. Some patients present with kidney stones, renal failure, alone or with the above, or as an intolerance/sensitivity to therapy (fluorouracil or azathioprine immunosupprcssion). These disorders can be detected from the abnormal metabolites in body fluids and/or altered enzyme activity. Abnormal cellular nucleotides or renal clearance may sometimes provide the only clue. Diagnosis can be difficult because of genetic heterogeneity and interference by blood transfusion, diet or drugs. Tests incorporating enzyme peak shifts and online diode-array detection are essential. Collaborative research is needed to improve the diagnosis and understanding of the metabolic basis for these sometimes devastating disorders and to apply this knowledge to the more common killers of mankind.