3-Methylglutaconic aciduria, a frequent but underrecognized finding in carbamoyl phosphate synthetase I deficiency

Abstract The urea cycle disorder carbamoyl phosphate synthetase I deficiencyis an important differential diagnosisin the encephalopathic neonate. This intoxication type inborn errorof metabolismoften leads to neonatal death or severe and irreversible damage of the central nervous system, even despite appropriate treatment. Timely diagnosis is crucial, but can be difficult on routine metabolite level. Here, we report ten neonates from eight families (finally) diagnosed with CPS1 deficiency at three tertiary metabolic centres. In seven of them the laboratory findings were dominated by significantly elevated urinary 3-methylglutaconic acid levels which complicated the diagnostic process. Our findings are both important for the differential diagnosisof patients with urea cycle disordersand also broaden the differential diagnosisof hyperammonemiaassociated with 3-methylglutaconic aciduria, which was earlier only reported in TMEM70 and SERAC1 defect.