Extract: Two previously described sisters with folic acid nondependent formiminoglutamic aciduria also excrete abnormally high amounts of hydantoin-5-propionic acid (HPA). HPA was identified by gas chromatography-mass spectrometry as the N,N′-bis-trimethylsilyl methyl ester- and N,O-permethyl derivatives. About 600 and 1,100 mmol HPA/mol creatinine, respectively, were found in 24-hr urine samples before and after ingestion of free histidine (three equal doses of 66 mg/kg each, with 4-hr intervals). The corresponding values in normal adults were 4.5 ±2.2 (n = 24) and 46.0 ± 16.4 mmol HPA/mol creatinine (n = 17) when measured by a new, highly specific mass fragmentographic method using deuterated HPA as the internal standard.Speculation: Formation of hydantoin-5-propionic acid from imidazolone propionic acid (ImOPA) by aldehyde oxidase represents a bypass at elevated concentrations of ImOPA caused, e.g., by formimino-L-glutamate:tetrahydrofolate-5-formiminotransferase (EC. 2.1.2.5) deficiency (as postulated for our cases), general or functional folate deficiency, or imidazolone propionic acid hydrolase deficiency (not yet detected). HPA excretion in urine measured by mass fragmentography may be a sensitive tool to detect such deficiencies and may complement or even replace the enzymatic measurement of formiminoglutamic acid excretion.
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