Molecular genetic analysis and phenotypic characteristics of a consanguineous family with glycogen storage disease type Ia

Abstract

Glycogen storage disease type-Ia (GSD-Ia) is a rare autosomal recessive disease caused by a mutation in the gene encoding glucose-6-phosphate-α (G6PC). The present study reported the case of a 3-month-old female Chinese patient with GSD-Ia born to consanguineous parents. The aim of the present study was to identify the precise mutation of the G6PC gene associated with this family and to describe the phenotypic characteristics of the patient. A comprehensive examination was performed on the patient, including physical examination, vein blood gas analysis, abdominal sonography and biochemical analyses. In addition, gene sequencing was performed on the coding region of the G6PC gene to identify the mutation. The patient was diagnosed with GSD-Ia and a G6PC missense mutation of c.518T>C (p.L173P) located in a highly conserved area was identified. The mutation is in a non-helical region of the protein, which previous studies have suggested should result in a lesser effect on G6PC enzymatic activity and milder phenotypic characteristics compared with mutations located in helical regions. However, the severity of the disease phenotype in the subject of the present study was inconsistent with that predicted from her genotype. The patient suffered from serious hypoglycemia, lactic acidosis, increased triglycerides, hepatic dysfunction, clear hepatomegaly and nephromegaly. The incidence of the p.L173P mutation may be relatively high in the Chinese population. Knowledge of the various phenotypic presentations of the p.L173P mutation may beneficial for future investigations.