Glycogen storage disease type Ia (GSD Ia) is an autosomal recessive disorder of glycogen metabolism caused by glucose-6-phosphatase (G6Pase) deficiency. The clinical manifestations of G6Pase deficiency include growth retardation, hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia and hyperuricemia. Many mutations of this gene have been found worldwide in various ethnic groups, establishing the molecular basis of GSD Ia. To elucidate a spectrum of the G6Pase gene mutations in Korean, we analyzed mutations in Korean patients with GSD Ia.

Both alleles of 9 unrelated GSD 1a patients were studied by PCR and direct DNA sequencing methods. In all patients, GSD 1a was diagnosed by the enzyme assay for the liver biopsy specimen.

In Korean, the most prevalent mutation was g727t substitution in exon 5, which has been reported to cause abnormal mRNA splicing: Sixteen out of 18 alleles were found to have this mutation. In addition, we identified one novel mutation, a c611g, converting a proline to an alanine at codon 178.

Our findings suggest that a screening for the g727t mutation by noninvasive molecular method can detect most cases of GSD Ia in Korean patients.