Analysis of GBE1 mutations via protein expression studies in glycogen storage disease type IV: A report on a non-progressive form with a literature review.

ABSTRACT: Background:Glycogen storage disease type IV (GSD IV), caused by GBE1 mutations, has a quite wide phenotypic variation. While the classic hepatic form and the perinatal/neonatal neuromuscular forms result in early mortality, milder manifestations include non-progressive form (NP-GSD IV) and adult polyglucosan body disease (APBD). Thus far, only one clinical case of a patient with compound heterozygous mutations has been reported for the molecular analysis of NP-GSD IV. This study aimed to elucidate the molecular basis in a NP-GSD IV patient via protein expression analysis and to obtain a clearer genotype-phenotype relationship in GSD IV. Case presentation:A Japanese boy presented hepatosplenomegaly at 2?years of age. Developmental delay, neurological symptoms, and cardiac dysfunction were not apparent. Observation of hepatocytes with periodic acid-Schiff-positive materials resistant to diastase, coupled with resolution of hepatosplenomegaly at 8?years of age, yielded a diagnosis of NP-GSD IV. Glycogen branching enzyme activity was decreased in erythrocytes. At 13?years of age, he developed epilepsy, which was successfully controlled by carbamazepine. Molecular analysis:In this study, we identified compound heterozygous GBE1 mutations (p.Gln46Pro and p.Glu609Lys). The branching activities of the mutant proteins expressed using E. coli were examined in a reaction with starch. The result showed that both mutants had approximately 50% activity of the wild type protein. Conclusion:This is the second clinical report of a NP-GSD IV patient with a definite molecular elucidation. Based on the clinical and genotypic overlapping between NP-GSD IV and APBD, we suggest both are in a continuum.

SUBMITTER: Iijima H 

PROVIDER: S-EPMC6140619 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature