We report a Korean patient with glycogen storage disease type 1b (GSD-1b) whose diagnosis was confirmed by liver biopsy and laboratory results. The patient presented with delay of puberty and short stature on admission and had typical clinical symptoms of GSD as well as chronic neutropenia and inflammatory bowel disease. Mutation analysis of the glucose 6-phosphate translocase 6-phosphate translocase (SLC37A4) gene revealed that the patient was a compound heterozygote of two different mutations including a deletion mutation (c.1042_1043delCT; L348fs) and a missense mutation (A148V). The L348fs mutation was inherited from the patient's father and has been reported in an Italian family with GSD-1b, while the A148V mutation was transmitted from the patient's mother and was a novel mutation. To the best of our knowledge, this is the first report of genetically confirmed case of GSD-1b in Korean.
Base Sequence ; DNA/chemistry/genetics ; DNA Mutational Analysis ; Glycogen Storage Disease Type I/enzymology/*genetics ; Humans ; Korea ; *Mutation, Missense ; Phosphotransferases/*genetics ; Research Support, Non-U.S. Gov't

UNLABELLEDGlycogen storage disease (GSD) type Ia is an autosomal recessive disorder caused by a deficiency of glucose-6-phosphatase (G6Pase). The gene that encodes G6Pase was mapped to 17q21. The molecular genetic basis of GSD type Ia in the mainland Chinese population has not been explored.

OBJECTIVETo analyze the G6Pase gene mutations, and to compare the phenotypic features and the response to the corn starch treatment among patients who share the same mutation.

METHODSWith the consent of the parents and their children, the authors studied 18 families with clinically diagnosed GSD type Ia from our long time follow-up groups. Direct DNA sequencing of all 5 exons and the exon-intron boundaries of G6Pase gene were done on the blood specimens. Seven of the 18 patients, male 2 and female 5, aged 1.5 to 16 years, were homozygous for same mutation. The clinical symptoms, signs and the serum biochemical values before and after treatment were compared in these 7 patients.

RESULTSThe 7 patients were homozygous of G-->T transversion at the nucleotide 727 in exon 5 (G727T), which has previously been reported to cause abnormal splicing. The parents were heterozygous of the G727T mutation. All the patients exhibited typical features of GSD type Ia with variable severity, including hypoglycemia, hepatomegaly, kidney enlargement, growth retardation, bleeding diathesis, lactic acidemia, hyperlipidemia, and hyperuricemia. Two of the patients had repeated hypoglycemic seizures before the age of 2 years. One had moderate splenomegaly when he came to our clinic at the age of 16, the spleen size was reduced to 2 cm below the left costal margin after 5-year treatment. His sister, homozygous of G727T, did not show splenomegaly. One had multiple hepatic adenoma since the age of 5 years. Four had 5-year-delayed bone age when they started treatment at the age of 9 to 16 years, the bone age reached normal after 2 - 3 years treatment. No matter when they started corn starch treatment, the height increase in the first year was most obvious with an average of 10 cm. All the patients had abnormal liver function before treatment, 5 had constant slightly elevated liver enzymes with the treatment. All had normal urinalysis test, but the urine beta(2)- microglobulin was elevated.

CONCLUSIONSG727T mutation may be the major cause of GSD type Ia in China. Patients with the same mutation could have variable phenotypic characteristics, and the response to the corn starch treatment was different. The diagnosis of GSD type Ia can be based on clinical and biochemical abnormalities combined with mutation analysis instead of enzyme assays on liver biopsy.

Adolescent ; Base Sequence ; Child ; Child, Preschool ; China ; DNA ; chemistry ; genetics ; DNA Mutational Analysis ; Family Health ; Female ; Glucose-6-Phosphatase ; genetics ; metabolism ; Glycogen Storage Disease Type I ; enzymology ; genetics ; pathology ; Homozygote ; Humans ; Infant ; Male ; Molecular Sequence Data ; Phenotype ; Point Mutation ; Polymerase Chain Reaction