A 59-year-old woman, with a medical history of intellectual disability after perinatal asphyxia, was admitted because of coma due to hyperammonemia after she was treated for a fracture of the pelvis. The ammonia level was 280 μM. Acquired disorders as explanation for the hyperammonemia were excluded. Metabolic investigations showed an elevated glutamine and alanine and low citrulline, suspect for a urea cycle defect (UCD). Orotic acid could not be demonstrated in urine. DNA investigations were negative for mutations or deletions in the OTC and CPS1 gene, but revealed a homozygous c.603G>C mutation in exon 2 of the N-acetylglutamate synthase (NAGS) gene (NM_153006.2:c.603G>C), which mandates p.Lys201Asn. This is a novel mutation in the NAGS gene.
After the diagnosis of NAGS deficiency was made carbamylglutamate was started in a low dose. In combination with mild protein restriction the ammonia level decreased to 26 μM.
This is one of the first patients in literature in whom the diagnosis of a UCD is made at such an advanced age. It is important for the adult physician to consider a metabolic disorder at every age.
Grunert SC, Villavicencio-Lorini P, Wermuth B, Lehnert W, Sass JO, Schwab KO (2013) Ornithine transcarbamylase deficiency combined with type 1 diabetes mellitus—a challenge in clinical and dietary management. J Diabetes Metab Disord 12(1):37CrossRefPubMedPubMedCentralGoogle Scholar
Morris AA, Richmond SW, Oddie SJ, Pourfarzam M, Worthington V, Leonard JV (1998) N-Acetylglutamate synthetase deficiency: favourable experience with carbamylglutamate. J Inherit Metab Dis 21(8):867–868CrossRefPubMedGoogle Scholar
Nakamura K, Kido J, Mitsubuchi H, Endo F (2014) Diagnosis and treatment of urea cycle disorder in Japan. Pediatr Int 56(4):506–509CrossRefPubMedGoogle Scholar
Roberts DL, Galbreath DA, Patel BM, Ingall TJ, Khatib A, Johnson DJ (2013) Hyperammonemic coma in an adult due to ornithine transcarbamylase deficiency. Case Rep Crit Care 2013:493216PubMedPubMedCentralGoogle Scholar
Schmidt E, Nuoffer JM, Haberle J et al (2005) Identification of novel mutations of the human N-acetylglutamate synthase gene and their functional investigation by expression studies. Biochim Biophys Acta 1740(1):54–59CrossRefPubMedGoogle Scholar
Serrano M, Martins C, Perez-Duenas B et al (2010) Neuropsychiatric manifestations in late-onset urea cycle disorder patients. J Child Neurol 25(3):352–358CrossRefPubMedGoogle Scholar
Summar ML, Barr F, Dawling S et al (2005) Unmasked adult-onset urea cycle disorders in the critical care setting. Crit Care Clin 21(4 Suppl):S1–S8CrossRefPubMedGoogle Scholar
Walker V (2009) Ammonia toxicity and its prevention in inherited defects of the urea cycle. Diabetes Obes Metab 11(9):823–835CrossRefPubMedGoogle Scholar
Grody WW, Chang RJ, Panagiotis NM, Matz D, Cederbaum SD (1994) Menstrual cycle and gonadal steroid effects on symptomatic hyperammonaemia of urea-cycle-based and idiopathic aetiologies. J Inherit Metab Dis 17(5):566–574CrossRefPubMedGoogle Scholar
Caldovic L, Morizono H, Tuchman M (2007) Mutations and polymorphisms in the human N-acetylglutamate synthase (NAGS) gene. Hum Mutat 28(8):754–759CrossRefPubMedGoogle Scholar
Tuchman M, Caldovic L, Daikhin Y et al (2008) N-Carbamylglutamate markedly enhances ureagenesis in N-acetylglutamate deficiency and propionic acidemia as measured by isotopic incorporation and blood biomarkers. Pediatr Res 64(2):213–217CrossRefPubMedPubMedCentralGoogle Scholar