Formiminoglutamic/hydantoinpropionic aciduria in two siblings

Abstract

Case Report 155 REFERENCES Gibson KM, Breuer J, Nyhan WL (1988a) 3-Hydroxymethylglutaryl-coenzyme A lyase deficiency: review of 18 reported patients. Eur J Pediatr 148: 180-186. Gibson KM, Breuer J, Kaiser K et al (1988b) 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: report of five new patients. J lnher Metab Dis 11: 76-87. Leupold D, Bojasch M, Jacobs C (1982) 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency in an infant with macrocephaly and mild metabolic acidosis. Eur J Pediatr 138: 73-76. J. Inher. Metab. Dis. 16 (1993) 155-156 -Folic acid non-dependent excessive formiminoglutamic aciduria (Figlu-uria) is an extremely rare disorder: only a handful of patients have been reported (Niederwieser et al 1974; Beck et al 1981; Duran et al 1981). The clinical presentations were somewhat variable, including features such as mild developmental delay .and seizures. Several biochemically affected subjects appeared to be symptom free. The index patient, a girl, was referred to the hospital at the age of 10 weeks when she had a 4-minute episode of neurological dysfunction with hypertonicity and breath holding. A similar attack had occurred 4 weeks previously. Epilepsy was unknown in the family and no precipitating circumstances could be traced. An EEG was normal. Haematological investigations did not reveal abnormalities; in particular, megaloblastic changes were absent (Hb 6.6 mmol/L, MCV 77 fl). Serum folate was increased: 65.6nmol/L (controls 7-23). Screening for inherited metabolic disorders by twodimensional thin-layer chromatography of urinary amino acids (Duran et al 1981) revealed a large spot in the position of glutamic acid. Quantitative analysis of amino acids with an LKB Alpha-plus amino acid analyser showed a normal excretion of glutamate. Pretreatment of the urine with an equal volume of 2 mol/L ammonia at room temperature for 4 hours caused a sharp rise of the glutamate concentration. The difference between these two values represented the Figlu concentration: 756 #mol/L; 525 #mol/mmol creatinine. Analysis of urinary organic acids disclosed only a trace of hydantoin-5-propionic acid (HPA): 11 #mol/L. In vivo histidine metabolism was tested by oral loading with 100 mg/kg L-histidine and measuring the 24-hour urinary excretion of Figlu and HPA. This resulted in a peak Figlu excretion of 6500 #mol/L and HPA excretion of 2130 #mol/L. The 24-hour metabolite excretion 1University Children's Hospital, 'Het Wilhelmina Kinderziekenhuis', Nieuwe Gracht 137, NL-3512 LK Utrecht; 2Antonius Ziekenhuis,