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Clin Chim Acta. 2015 Apr 15;444:50-3. doi: 10.1016/j.cca.2015.02.008. Epub 2015 Feb 11.

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.

Author information

1
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
2
Department of Laboratory Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea.
3
Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Republic of Korea. Electronic address: bhchoe@knu.ac.kr.
4
Department of Laboratory Medicine, Konkuk University College of Medicine, Konkuk University Hospital, Seoul, Republic of Korea.
5
Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
6
Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
7
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: nayadoo@hanmail.net.

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.

METHODS AND 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.

KEYWORDS:

Congenital disorders of glycosylation; Genetic diagnosis; Inherited metabolic diseases; PMM2; Whole-exome sequencing

PMID:
25681648
DOI:
10.1016/j.cca.2015.02.008
[Indexed for MEDLINE]

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