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

作者：Choi Rihwa; Woo Hye In; Choe Byung Ho^*; Park Seungman; Yoon Yeomin; Ki Chang Seok; Lee Soo Youn; Kim Jong Won; Song Junghan; Kim Dong Sub; Kwon Soonhak; Park Hyung Doo

来源：Clinica Chimica Acta, 2015, 444: 50-53.

DOI：10.1016/j.cca.2015.02.008

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

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 GM) 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 la (CDG-Ia: PMM2-CDG).
Conclusions: We successfully applied exome sequencing to diagnose the first reported Korean patient with COG-la, 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.

• 出版日期2015-4-15