Molecular, Biochemical, and Clinical Characterization of Thirteen Patients with Glycogen Storage Disease 1a in Malaysia
Background. Glycogen storage disease type 1a (GSD1a) is a rare autosomal recessive metabolic disorder characterized by hypoglycaemia, growth retardation, lactic acidosis, hepatomegaly, hyperlipidemia, and nephromegaly. GSD1a is caused by a mutation in the G6PC gene encoding glucose-6-phosphatase (G6...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Genetics Research |
| Online Access: | http://dx.doi.org/10.1155/2022/5870092 |
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| author | Siti Aishah Abdul Wahab Yusnita Yakob Mohd Khairul Nizam Mohd Khalid Noraishah Ali Huey Yin Leong Lock Hock Ngu |
| author_facet | Siti Aishah Abdul Wahab Yusnita Yakob Mohd Khairul Nizam Mohd Khalid Noraishah Ali Huey Yin Leong Lock Hock Ngu |
| author_sort | Siti Aishah Abdul Wahab |
| collection | DOAJ |
| description | Background. Glycogen storage disease type 1a (GSD1a) is a rare autosomal recessive metabolic disorder characterized by hypoglycaemia, growth retardation, lactic acidosis, hepatomegaly, hyperlipidemia, and nephromegaly. GSD1a is caused by a mutation in the G6PC gene encoding glucose-6-phosphatase (G6Pase); an enzyme that catalyses the hydrolysis of glucose-6-phosphate (G6P) to phosphate and glucose. Objective. To elaborate on the clinical findings, biochemical data, molecular genetic analysis, and short-term prognosis of 13 GSD1a patients in Malaysia. Methods. The information about 13 clinically classified GSD1a patients was retrospectively studied. The G6PC mutation analysis was performed by PCR-DNA sequencing. Results. Patients were presented with hepatomegaly (92%), hypoglycaemia (38%), poor weight gain (23%), and short stature (15%). Mutation analysis revealed nine heterozygous mutations; eight previously reported mutations (c.155 A > T, c.209 G > A, c.226 A > T, c.248 G > A, c.648 G > T, c.706 T > A, c.1022 T > A, c.262delG) and a novel mutation (c.325 T > C). The most common mutation found in Malaysian patients was c.648 G > T in ten patients (77%) of mostly Malay ethnicity, followed by c.248 G > A in 4 patients of Chinese ethnicity (30%). A novel missense mutation (c.325 T > C) was predicted to be disease-causing by various in silico software. Conclusions. The establishment of G6PC molecular genetic testing will enable the detection of presymptomatic patients, assisting in genetic counselling while avoiding the invasive methods of liver biopsy. |
| format | Article |
| id | doaj-art-22f071b3008a432793afed0b343a722e |
| institution | Kabale University |
| issn | 1469-5073 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Genetics Research |
| spelling | doaj-art-22f071b3008a432793afed0b343a722e2025-02-03T01:20:35ZengWileyGenetics Research1469-50732022-01-01202210.1155/2022/5870092Molecular, Biochemical, and Clinical Characterization of Thirteen Patients with Glycogen Storage Disease 1a in MalaysiaSiti Aishah Abdul Wahab0Yusnita Yakob1Mohd Khairul Nizam Mohd Khalid2Noraishah Ali3Huey Yin Leong4Lock Hock Ngu5Molecular Diagnostics UnitMolecular Diagnostics UnitIEM & Genetic UnitDepartment of GeneticsDepartment of GeneticsDepartment of GeneticsBackground. Glycogen storage disease type 1a (GSD1a) is a rare autosomal recessive metabolic disorder characterized by hypoglycaemia, growth retardation, lactic acidosis, hepatomegaly, hyperlipidemia, and nephromegaly. GSD1a is caused by a mutation in the G6PC gene encoding glucose-6-phosphatase (G6Pase); an enzyme that catalyses the hydrolysis of glucose-6-phosphate (G6P) to phosphate and glucose. Objective. To elaborate on the clinical findings, biochemical data, molecular genetic analysis, and short-term prognosis of 13 GSD1a patients in Malaysia. Methods. The information about 13 clinically classified GSD1a patients was retrospectively studied. The G6PC mutation analysis was performed by PCR-DNA sequencing. Results. Patients were presented with hepatomegaly (92%), hypoglycaemia (38%), poor weight gain (23%), and short stature (15%). Mutation analysis revealed nine heterozygous mutations; eight previously reported mutations (c.155 A > T, c.209 G > A, c.226 A > T, c.248 G > A, c.648 G > T, c.706 T > A, c.1022 T > A, c.262delG) and a novel mutation (c.325 T > C). The most common mutation found in Malaysian patients was c.648 G > T in ten patients (77%) of mostly Malay ethnicity, followed by c.248 G > A in 4 patients of Chinese ethnicity (30%). A novel missense mutation (c.325 T > C) was predicted to be disease-causing by various in silico software. Conclusions. The establishment of G6PC molecular genetic testing will enable the detection of presymptomatic patients, assisting in genetic counselling while avoiding the invasive methods of liver biopsy.http://dx.doi.org/10.1155/2022/5870092 |
| spellingShingle | Siti Aishah Abdul Wahab Yusnita Yakob Mohd Khairul Nizam Mohd Khalid Noraishah Ali Huey Yin Leong Lock Hock Ngu Molecular, Biochemical, and Clinical Characterization of Thirteen Patients with Glycogen Storage Disease 1a in Malaysia Genetics Research |
| title | Molecular, Biochemical, and Clinical Characterization of Thirteen Patients with Glycogen Storage Disease 1a in Malaysia |
| title_full | Molecular, Biochemical, and Clinical Characterization of Thirteen Patients with Glycogen Storage Disease 1a in Malaysia |
| title_fullStr | Molecular, Biochemical, and Clinical Characterization of Thirteen Patients with Glycogen Storage Disease 1a in Malaysia |
| title_full_unstemmed | Molecular, Biochemical, and Clinical Characterization of Thirteen Patients with Glycogen Storage Disease 1a in Malaysia |
| title_short | Molecular, Biochemical, and Clinical Characterization of Thirteen Patients with Glycogen Storage Disease 1a in Malaysia |
| title_sort | molecular biochemical and clinical characterization of thirteen patients with glycogen storage disease 1a in malaysia |
| url | http://dx.doi.org/10.1155/2022/5870092 |
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