Glycogen storage disease type Ⅰb (GSDⅠb, MIM: 232220) is an autosomal recessive inborn error of metabolism caused by deficiency of the glucose-6-phosphate translocase. The clinical manifestations include symptoms and signs of both the typical GSDⅠa, including hepatomegaly, fasting hypoglycemia, lactic acidemia and hyperlipedemia, and the dysfunction of neutrophils of recurrent infection and neutropenia. More than 84 mutations have been identified since the discovery of the SLC37A4 gene as the disease causing gene. Up to date, 5 mutations in 4 Chinese patients were reported from Hong Kang and Taiwan. In order to see the spectrum of the SLC37A4 gene mutations and the correlation between genotype and phenotype in patients with GSDⅠb of the mainland of China, the authors investigated 17 GSDⅠb patients from 15 families in this study.

Data of 17 patients from 12 provinces, 11 male and 6 female, aged 6 months to 35 years, were collected from the genetic clinics of Peking Union Medical College Hospital from Oct. 2006 to Mar. 2009. All of them were Han Chinese in ethnicity. Consanguineous status was confirmed in 2 unrelated patients. All patients were presented with hepatomegaly, fasting hypoglycemia, lactic acidemia, hyperlipedemia and neutropenia with variable frequency of infections. The full coding exons, their relevant exon-intron boundaries, and the 5′- and 3′-flanking regions of the SLC37A4 gene were amplified and directly sequenced. RT-PCR was performed to verify the effect of the 2 novel splicing mutations.

A total of 11 mutations were identified in 15 families. Four mutations, p. Gly149Glu, p.Pro191Leu, p.Arg415X and c. 1042_1043 del CT, were previously reported, and seven mutations, p. Leu23Arg, p. Gly115Arg, p. Gly281Val, p. Arg415Gly, c. 784+ 1G>A, c. 870+ 5G>A and c. 1014_1120del107, were novel. The frequent mutations are p. Pro191Leu, p.Gly149Glu and c. 870+ 5G>A, accounting for 37%, 15% and 11% of mutant alleles respectively. RT-PCR analysis of novel mutation c. 784+ 1G>A confirmed the splicing of exon 5 of 159 bp, causing inframe deletion. While mutation c. 870+ 5G>A was proved to cause exon 6, 86 bp, deletion causing frame-shift. Among 15 families, 12 genotypes were identified, including 3 with homozygous mutation and 9 with compound heterozygous mutations. Homozygous p. Pro191Leu mutation was the only genotype detected in more than 1 family and was found in 4 unrelated families, including 1 patient from consanguineous marriage.

A total of 11 SLC37A4 gene mutations were identified in 15 families of the mainland of China. The frequent mutations are p. Pro191Leu, p.Gly149Glu and c. 870+ 5G>A. The number of Chinese SLC37A4 gene mutations was extended from 5 to 14.

Glycogen storage disease type Ⅰ; Glucose-6-phosphase; SLC37A4 gene; Gene; Mutation