Biochemical and molecular investigation of two Korean patients with glycogen storage disease type III

Abstract

Glycogen storage disease type III (GSD-III) is an inborn error of glycogen metabolism caused by a deficiency of the glycogen debranching enzyme, amylo-1,6-glucosidase,4-alpha-glucanotransferase (AGL). Here, we describe two unrelated Korean patients with GSD-III and review their clinical and laboratory findings. The patients were 18- and 11-month-old girls. They presented with hepatosplenomegaly, developmental delay and hypotonia. The routine laboratory findings showed an elevated serum aspartate aminotransferase, alanine aminotransferase, creatine kinase and triglyceride levels. The blood lactate and uric acid levels were within normal limits. PCR and direct sequencing were performed to determine genetic findings. Glycogen quantitation was markedly increased and AGL activity was undetectable in both patients. Sequence analysis of the AGL gene showed that both patients were compound heterozygotes for c.853C>T (p.R285X) and c.1735+1G>T in one patient, and c.2894_2896delGGAinsTG and c.4090G>C (p.D1364H) in the other patient. The c.2894_2896delGGAinsTG and c.4090G>C (p.D1364H) mutation was a novel finding. GSD-III should be ruled out when a patient presents with hepatic abnormalities, hypoglycemia, myopathy and hyperlipidemia. This is the first report of confirmation of GSD-III in Korean patients by biochemical and genetic findings.