Case Report Early infantile presentation of 3-methylglutaconic aciduria type 1 with a novel mutation in AUH gene: A case report and literature review Ali Reza Tavasoli a , Reza Shervin Badv a , Johannes Zschocke b , Mahmood Reza Ashrafi a , Parastoo Rostami c,⇑ a Pediatric Neurology Division, Neurometabolic Registry Center, Children’s Medical Center, Tehran University of Medical Science, Tehran, Iran b Division of Human Genetics, Medical University Innsbruck, 6020 Innsbruck, Austria c Division of Endocrinology and Metabolism, Department of Pediatrics, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran Received 29 January 2017; received in revised form 29 March 2017; accepted 2 April 2017 Abstract 3-Methylglutaconic aciduria is a member of inborn errors of leucine metabolism pathway. 3-Methylglutaconic aciduria type I (MGA1) causes neurological problems which are present during infancy or childhood but the diagnosis may be delayed until adult- hood. Here we report a 3 years old patient with developmental delay from a relative parent’s that his medical evaluations include analyses of urinary organic acid and blood acylcarnitine showed high level of 3-methylglutacoic acid, 3-hydroxyisovaleric acid and increased level of 3-hydroxyisovalerylcarnitine respectively. Further evaluation and genetic tests revealed a novel homozygous muta- tion of variant c.179del G (p.Gly60Valfs*12) in exon 1 of the AUH gene that was compatible with the diagnosis of MGA1. In seg- regation analysis of his family, both parents were heterozygous for the respective mutation, confirming obligate parental carrier status and segregation of the mutation. Ó 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. Keywords: 3-Methylglutaconic aciduria type 1; Developmental delay; 3-Methylglutaconyl-CoA hydratase 1. Introduction 3-Methylglutaconic aciduria type 1 (MGA1, OMIM #250950) is a rare autosomal recessive inborn error of leucine metabolism that has only been identified in very few individuals. Five inherited disorders are known to be associated with excessive excretion of 3- methylglutaconic acid (MGA) in the urine that caused by mutations in different genes include: MGA1 due to deficiency of the 3-methylglutaconyl-CoA hydratase activity, Barth syndrome (MGA2, MIM# 302060) caused by a deficiency of tafazzin, Costeff optic atrophy syndrome (MGA3, MIM# 258501) caused by a defi- ciency unknown protein and 3-Methylglutaconic acid- uria type IV and V are still not well delineated [1,2]. Patients with MGA1 excrete the highest level of 3- methylglutaconic acid and two metabolites 3- methylglutaric and 3-hydroxyisovaleric acids in urine than other types. Clinical manifestations of MGA1 are heterogeneous with a wide spectrum from asymptomatic condition to mild neurological impairment, speech http://dx.doi.org/10.1016/j.braindev.2017.04.007 0387-7604/Ó 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. ⇑ Corresponding author at: Department of Pediatrics, Children’s Medical Center, Tehran University of Medical Sciences, 62 Gharib St, 14194 Tehran, Iran. Fax: +98 21 66923054. E-mail address: drp_rostami@yahoo.com (P. Rostami). www.elsevier.com/locate/braindev Brain & Development xxx (2017) xxx–xxx Please cite this article in press as: Tavasoli AR et al. Early infantile presentation of 3-methylglutaconic aciduria type 1 with a novel mutation in AUH gene: A case report and literature review. Brain Dev (2017), http://dx.doi.org/10.1016/j.braindev.2017.04.007