Predominance of the c.648G > T G6PC gene mutation and late complications in Korean patients with glycogen storage disease type Ia
Abstract Background Glycogen storage disease (GSD) Ia, caused by mutations in the glucose-6-phosphatase (G6PC) gene, is characterized by hepatomegaly, hypoglycemia, lactic acidosis, dyslipidemia, and hyperuricemia. This study aimed to investigate clinical and molecular features and late complication...
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-020-1321-0 |
| _version_ | 1819178282705223680 |
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| author | Yoo-Mi Kim Jin-Ho Choi Beom-Hee Lee Gu-Hwan Kim Kyung-Mo Kim Han-Wook Yoo |
| author_facet | Yoo-Mi Kim Jin-Ho Choi Beom-Hee Lee Gu-Hwan Kim Kyung-Mo Kim Han-Wook Yoo |
| author_sort | Yoo-Mi Kim |
| collection | DOAJ |
| description | Abstract Background Glycogen storage disease (GSD) Ia, caused by mutations in the glucose-6-phosphatase (G6PC) gene, is characterized by hepatomegaly, hypoglycemia, lactic acidosis, dyslipidemia, and hyperuricemia. This study aimed to investigate clinical and molecular features and late complications in Korean patients with GSD Ia. Results Fifty-four Korean patients (33 males and 21 females) from 47 unrelated families, who were diagnosed with GSD Ia, based on genetic and biochemical data, between 1999 and 2017, were included in this study. The median age at diagnosis was 3.9 years (range: 5 months to 42 years), and the follow-up period was 8.0 ± 6.8 years. Most patients presented with hepatomegaly during infancy, but hypoglycemic symptoms were not predominant. Genetic analysis showed that all the patients had at least one c.648G > T allele. Homozygous c.648G > T mutations in the G6PC gene were identified in 34 families (72.3%), and compound heterozygotes with c.648G > T were found in the other families. The allele frequency of c.648G > T was 86.2% (81/94), and p.F51S, p.R83H, p.G122D, p.Y128*, p.G222R, and p.T255A were identified. Of 26 adult patients, 14 had multiple hepatic adenomas, and two were diagnosed with hepatocellular carcinoma. Thirteen patients showed renal complications, and seven patients presented gout, despite preventive allopurinol treatment. Twelve patients had osteoporosis, and two patients had pulmonary hypertension. The final heights were 157.9 cm (standard deviation score: − 3.1) in males and 157.8 cm (standard deviation score: − 0.6) in females. Conclusion In our Korean patients with GSD Ia, the most common mutation in the G6PC gene was c.648G > T, suggesting a founder effect. Because of only mild hypoglycemia, the patients tended to be diagnosed late. Thus, adult patients with GSD Ia eventually developed diverse and serious complications, which indicates a need for careful monitoring and proper management of this disease. |
| first_indexed | 2024-12-22T21:40:05Z |
| format | Article |
| id | doaj.art-b0885108a3304f70a31d88444de9a95e |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-22T21:40:05Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
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| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-b0885108a3304f70a31d88444de9a95e2022-12-21T18:11:39ZengBMCOrphanet Journal of Rare Diseases1750-11722020-02-011511810.1186/s13023-020-1321-0Predominance of the c.648G > T G6PC gene mutation and late complications in Korean patients with glycogen storage disease type IaYoo-Mi Kim0Jin-Ho Choi1Beom-Hee Lee2Gu-Hwan Kim3Kyung-Mo Kim4Han-Wook Yoo5Department of Pediatrics, Chungnam National University Hospital, Chungnam National University, College of MedicineDepartment of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan, College of MedicineDepartment of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan, College of MedicineDepartment of Medical Genetics, Asan Medical Center Children’s Hospital, University of Ulsan, College of MedicineDepartment of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan, College of MedicineDepartment of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan, College of MedicineAbstract Background Glycogen storage disease (GSD) Ia, caused by mutations in the glucose-6-phosphatase (G6PC) gene, is characterized by hepatomegaly, hypoglycemia, lactic acidosis, dyslipidemia, and hyperuricemia. This study aimed to investigate clinical and molecular features and late complications in Korean patients with GSD Ia. Results Fifty-four Korean patients (33 males and 21 females) from 47 unrelated families, who were diagnosed with GSD Ia, based on genetic and biochemical data, between 1999 and 2017, were included in this study. The median age at diagnosis was 3.9 years (range: 5 months to 42 years), and the follow-up period was 8.0 ± 6.8 years. Most patients presented with hepatomegaly during infancy, but hypoglycemic symptoms were not predominant. Genetic analysis showed that all the patients had at least one c.648G > T allele. Homozygous c.648G > T mutations in the G6PC gene were identified in 34 families (72.3%), and compound heterozygotes with c.648G > T were found in the other families. The allele frequency of c.648G > T was 86.2% (81/94), and p.F51S, p.R83H, p.G122D, p.Y128*, p.G222R, and p.T255A were identified. Of 26 adult patients, 14 had multiple hepatic adenomas, and two were diagnosed with hepatocellular carcinoma. Thirteen patients showed renal complications, and seven patients presented gout, despite preventive allopurinol treatment. Twelve patients had osteoporosis, and two patients had pulmonary hypertension. The final heights were 157.9 cm (standard deviation score: − 3.1) in males and 157.8 cm (standard deviation score: − 0.6) in females. Conclusion In our Korean patients with GSD Ia, the most common mutation in the G6PC gene was c.648G > T, suggesting a founder effect. Because of only mild hypoglycemia, the patients tended to be diagnosed late. Thus, adult patients with GSD Ia eventually developed diverse and serious complications, which indicates a need for careful monitoring and proper management of this disease.https://doi.org/10.1186/s13023-020-1321-0Glycogen storage diseaseG6PCAdultComplication |
| spellingShingle | Yoo-Mi Kim Jin-Ho Choi Beom-Hee Lee Gu-Hwan Kim Kyung-Mo Kim Han-Wook Yoo Predominance of the c.648G > T G6PC gene mutation and late complications in Korean patients with glycogen storage disease type Ia Orphanet Journal of Rare Diseases Glycogen storage disease G6PC Adult Complication |
| title | Predominance of the c.648G > T G6PC gene mutation and late complications in Korean patients with glycogen storage disease type Ia |
| title_full | Predominance of the c.648G > T G6PC gene mutation and late complications in Korean patients with glycogen storage disease type Ia |
| title_fullStr | Predominance of the c.648G > T G6PC gene mutation and late complications in Korean patients with glycogen storage disease type Ia |
| title_full_unstemmed | Predominance of the c.648G > T G6PC gene mutation and late complications in Korean patients with glycogen storage disease type Ia |
| title_short | Predominance of the c.648G > T G6PC gene mutation and late complications in Korean patients with glycogen storage disease type Ia |
| title_sort | predominance of the c 648g t g6pc gene mutation and late complications in korean patients with glycogen storage disease type ia |
| topic | Glycogen storage disease G6PC Adult Complication |
| url | https://doi.org/10.1186/s13023-020-1321-0 |
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