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

Dariusz Rokicki, Magdalena Pajdowska, Joanna Trubicka, Meow-Keong Thong, Elżbieta Ciara, Dorota Piekutowska-Abramczuk, Maciej Pronicki, Roman Sikora, Rijad Haidar, Mariusz Ołtarzewski, Ewa Jabłońska, Premala Muthukumarasamy, Pavai Sthaneswar, Chin-Seng Gan, Małgorzata Krajewska-Walasek, Rosalba Carrozzo, Daniela Verrigni, Michela Semeraro, Cristiano Rizzo, Roberta Taurisano, Bader Alhaddad, Reka Kovacs-Nagy, Tobias B Haack, Carlo Dionisi-Vici, Ewa Pronicka, Saskia B Wortmann

Journal: Clinica chimica acta; international journal of clinical chemistry 2018;471():95-100

PMID: 28526534

Full Text on Elsevier Science View on PubMed

Abstract

The urea cycle disorder carbamoyl phosphate synthetase I deficiency is an important differential diagnosis in the encephalopathic neonate. This intoxication type inborn error of metabolism often 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 diagnosis of patients with urea cycle disorders and also broaden the differential diagnosis of hyperammonemia associated with 3-methylglutaconic aciduria, which was earlier only reported in TMEM70 and SERAC1 defect.

Address: Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.; Department of Biochemistry and Experimental Medicine, The Children's Memorial Health Institute, Warsaw, Poland.; Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.; Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.; Department of Pathology, The Children's Memorial Health Institute, Warsaw, Poland.; Ward of Neonatal Pathology and Intensive Care, Regional Specialist Hospital, Częstochowa, Poland.; District Hospital, Biała Podlaska, Poland.; Institute of Mother and Child, Warsaw, Poland.; Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.; Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.; Division of Metabolism, Bambino Gesù Children's Hospital, Rome, Italy.; Department of Human Genetics, Technical University Munich, Munich, Germany; Institute of Human Genetics, Helmholtz Zentrum, Neuherberg, Germany.; Department of Human Genetics, Technical University Munich, Munich, Germany; Institute of Human Genetics, Helmholtz Zentrum, Neuherberg, Germany; Institute of Medical Genetics and Applied Genomics, University of Tübingen, 72076 Tübingen, Germany.; Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland; Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.; Department of Human Genetics, Technical University Munich, Munich, Germany; Institute of Human Genetics, Helmholtz Zentrum, Neuherberg, Germany; Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), Salzburg, Austria. Electronic address: [email protected].

DOI: 10.1016/j.cca.2017.05.023

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MeSH Terms: Carbamoyl-Phosphate Synthase I Deficiency Disease, Female, Glutarates, Humans, Infant, Newborn, Male, Mutation, Pedigree