title: Aspartylglucosaminuria caused by a novel homozygous mutation in the AGA gene was identified by an exome-first approach in a patient from Japan.
abstract: BACKGROUND
  Aspartylglucosaminuria (AGU) is an autosomal recessive lysosomal storage disorder caused by a deficiency of the lysosomal enzyme, aspartylglucosaminidase (AGA). This disorder is rare in the general population except in Finland. Since the most characteristic feature of this disorder is a progressive developmental regression, patients often show no specific symptoms in the initial stages, and thus early diagnosis is often challenging.
  
  
  METHODS
  We encountered a 16-year-old boy who began to show difficulties in his speech at the age of 6years. Due to a mild regression in his development, he gradually lost common daily abilities. His diagnosis was first obtained through exome sequencing that identified a novel homozygous mutation in the AGA gene. This result was reasonable because of parental consanguinity. Reduced enzymatic activity of AGA was then confirmed. His urine was retrospectively screened by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and a specific pattern of abnormal metabolites was identified.
  
  
  CONCLUSIONS
  Because both exome sequencing and MALDI-TOF-MS screening are adaptable and comprehensive, future combinatory use of these methods would be useful for diagnosis of rare inborn errors of metabolism such as AGU.
authors.affiliation: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan; Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan. Electronic address: yamamoto.toshiyuki@twmu.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan; Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.affiliation: Department of Pediatrics, Minami Kyushu National Hospital, Aira, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Matsufuji
authors.affiliation: Department of Clinical Laboratory Medicine, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Mashima
authors.affiliation: Department of Clinical Laboratory Medicine, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Sakai
authors.affiliation: Department of Clinical Laboratory Medicine, National Center for Child Health and Development, Tokyo, Japan; Center for Lysosomal Storage Diseases, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Torayuki
authors.initials: T
authors.lastname: Okuyama
mesh_terms: D000293:Adolescent; D054880:Aspartylglucosaminuria / Q000000981:diagnostic imaging / Q000235:genetics*; D001227:Aspartylglucosylaminase / Q000235:genetics* / Q000378:metabolism; D059472:Exome / Q000235:genetics; D006801:Humans; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013788:Thalamus / Q000000981:diagnostic imaging
chemical_list: D001227:Aspartylglucosylaminase
keywords: Aspartylglucosaminidase (AGA); Aspartylglucosaminuria (AGU); Developmental regression; Exome sequencing; Lysosomal storage disorder; Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS)