Case Report Mucolipidosis IV: A milder form with novel mutations and serial MRI findings Takashi Shiihara a,⇑ , Mio Watanabe a , Kengo Moriyama a , Yasuhiro Maruyama b , Atsuo Kikuchi c , Natsuko Arai-Ichinoi c , Mitsugu Uematsu c , Kiyoko Sameshima d a Department of Neurology, Gunma Children’s Medical Center, Gunma 377-8577, Japan b Department of Ophthalmology, Kiryu Kosei General Hospital, Gunma 376-0034, Japan c Department of Pediatrics, Tohoku University School of Medicine, Sendai 980-8574, Japan d Division of Medical Genetics, Gunma Children’s Medical Center, Gunma 377-8577, Japan Received 21 November 2015; received in revised form 21 January 2016; accepted 13 February 2016 Abstract Background: Mucolipidosis IV (MLIV; OMIM #252650) is an autosomal recessive lysosomal storage disorder, frequently observed in the Ashkenazi Jewish population. MLIV typically results in intellectual disability, corneal opacities, and delayed motor milestones during infancy, with a relatively static course. To date, reports of MLIV in other ethnic groups have been sparse. Patient: The present study is a case report of a 9-year-old Japanese boy, diagnosed via whole-exome sequencing, with compound heterozygous mutations of MCOLN1 (OMIM * 605248): c.410T>C (p.Leu137Pro) and c.802_803delAG (p.Ser268Trpfs*17). Although his clinical course was mild (due to a lack of corneal clouding), other relevant features were present. These included strabismus, white matter signal abnormalities, and a hypoplastic corpus callosum at 2 years of age. After a molecular diagnosis, a markedly elevated serum gastrin level (which is also common in MLIV) was confirmed. Discussion: The present results suggest that MLIV could be added as a differential diagnosis for white matter disorders, regard- less of ethnicity. Beyond neurological or ophthalmologic findings, serum gastrin could be a useful diagnostic marker for MLIV. Ó 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. Keywords: Mucolipidosis IV; MCOLN1; White matter disorders; Hypoplastic corpus callosum; Serum gastrin; Magnetic resonance imaging 1. Introduction Mucolipidosis IV (MLIV) (OMIM #252650) is an autosomal recessive lysosomal storage disorder, fre- quently found among the Ashkenazi Jewish population. MLIV typically results in intellectual disability, corneal opacities, and delayed motor milestones during infancy [1]. Since the causative gene—MCOLN1—was identified in 2000, more than 20 mutations have been reported (Human Gene and Mutation Database; http://www. hgmd.cf.ac.uk/) [2]. However, reports from other ethnic groups remain sparse [3]. A recent study included our current patient (patient number 15 out of 26 children with a presumed genetic white matter disorder), who presented with limited information [4]. In other words, this could be the first report of a Japanese MLIV patient. Therefore, the goal of the present report was to provide more details of our MLIV patient and reveal possible diagnostic clues. http://dx.doi.org/10.1016/j.braindev.2016.02.009 0387-7604/Ó 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. ⇑ Corresponding author at: Department of Neurology, Gunma Children’s Medical Center, 779 Shimohakoda, Hokkitsu-machi, Shibukawa, Gunma 377-8577, Japan. Tel.: +81 279 52 3551; fax: +81 279 52 2045. E-mail address: shiihara-ind@umin.net (T. Shiihara). www.elsevier.com/locate/braindev Brain & Development xxx (2016) xxx–xxx Please cite this article in press as: Shiihara T et al. Mucolipidosis IV: A milder form with novel mutations and serial MRI findings. Brain Dev (2016), http://dx.doi.org/10.1016/j.braindev.2016.02.009