title: Application of whole exome sequencing to a rare inherited metabolic disease with neurological and gastrointestinal manifestations: a congenital disorder of glycosylation mimicking glycogen storage disease.
abstract: BACKGROUND
  Rare inherited metabolic diseases with neurological and gastrointestinal manifestations can be misdiagnosed as other diseases or remain as disorders with indeterminate etiologies. This study aims to provide evidence to recommend the utility of whole exome sequencing in clinical diagnosis of a rare inherited metabolic disease.
  
  
  RESULTS
  A 4-month-old female baby visited an outpatient clinic due to poor weight gain, repeated seizure-like episodes, developmental delay, and unexplained hepatomegaly with abnormal liver function test results. Although liver biopsy revealed moderate fibrosis with a suggested diagnosis of glycogen storage disease (GSD), no mutations were identified either by single gene approach for GSD (G6PC and GAA) or by next generation sequencing panels for GSD (including 21 genes). Whole exome sequencing of the patient revealed compound heterozygous mutations of PMM2: c.580C>T (p.Arg194*) and c.713G>C (p.Arg238Pro) which mutations were associated with congenital disorder of glycosylation Ia (CDG-Ia: PMM2-CDG).
  
  
  CONCLUSIONS
  We successfully applied exome sequencing to diagnose the first reported Korean patient with CDG-Ia, which was misdiagnosed as GSD. Whole exome sequencing may prove to be the preferred strategy for analysis of clinical features that do not readily suggest a specific diagnosis, such as those observed in inherited metabolic diseases, including CDG.
authors: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Rihwa
authors: R
authors: Choi
authors: Department of Laboratory Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea.
authors: Hye In
authors: HI
authors: Woo
authors: Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Republic of Korea. Electronic address: bhchoe@knu.ac.kr.
authors: Byung-Ho
authors: BH
authors: Choe
authors: Department of Laboratory Medicine, Konkuk University College of Medicine, Konkuk University Hospital, Seoul, Republic of Korea.
authors: Seungman
authors: S
authors: Park
authors: Department of Laboratory Medicine, Konkuk University College of Medicine, Konkuk University Hospital, Seoul, Republic of Korea.
authors: Yeomin
authors: Y
authors: Yoon
authors: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Chang-Seok
authors: CS
authors: Ki
authors: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Soo-Youn
authors: SY
authors: Lee
authors: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Jong-Won
authors: JW
authors: Kim
authors: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors: Junghan
authors: J
authors: Song
authors: Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors: Dong Sub
authors: DS
authors: Kim
authors: Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors: Soonhak
authors: S
authors: Kwon
authors: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: nayadoo@hanmail.net.
authors: Hyung-Doo
authors: HD
authors: Park
mesh_terms: D018981:Congenital Disorders of Glycosylation / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005260:Female; D005767:Gastrointestinal Diseases / Q000235:genetics*; D006008:Glycogen Storage Disease / Q000235:genetics*; D006031:Glycosylation; D006801:Humans; D007223:Infant; D009154:Mutation; D009422:Nervous System Diseases / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques; D017875:Phosphotransferases (Phosphomutases) / Q000172:deficiency* / Q000235:genetics
chemical_list: D017875:Phosphotransferases (Phosphomutases); C519582:phosphomannomutase 2, human
keywords: Congenital disorders of glycosylation; Genetic diagnosis; Inherited metabolic diseases; PMM2; Whole-exome sequencing