Affiliations 

  • 1 Molecular Diagnostics Unit, Specialised Diagnostic Centre, Institute for Medical Research, National Institute of Health, Ministry of Health, Jalan Pahang 50586, Kuala Lumpur, Malaysia
  • 2 IEM & Genetic Unit, Nutrition Metabolic and Cardiovascular Research Centre, Institute for Medical Research, National Institute of Health, Ministry of Health, Kuala Lumpur, Malaysia
  • 3 Department of Genetics, Hospital Kuala Lumpur, Ministry of Health, Kuala Lumpur, Malaysia
Genet Res (Camb), 2022;2022:5870092.
PMID: 36160031 DOI: 10.1155/2022/5870092

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.