A 24-year-old male was admitted due to recurrent redness, swelling, fever and pain in the ankle, frequently accompanied by hungry feeling. Dual energy CT scans showed multiple small gouty stones in the posterior edge of the bilateral calcaneus and in the space between the bilateral metatarsophalangeal joints. The laboratory examination results indicated hyperlipidemia, high lactate lipids, and low fasting blood glucose. Histopathology of liver biopsy showed significant glycogen accumulation. The results of gene sequencing revealed the compound heterozygous mutations of the <i>G6PCi> gene c.248G>A (p.Arg83His) and c.238T>A (p.Phe80Ile) in the proband. The c.248G>A mutation was from mother and the c.238T>A mutation was from father. The diagnosis of glycogen storage disease type Ⅰa was confirmed. After giving a high starch diet and limiting monosaccharide intake, as well as receiving uric acid and blood lipids lowering therapy, the condition of the patient was gradually stabilized. After a one-year follow-up, there were no acute episodes of gout and a significant improvement in hungry feeling in the patient.
Male ; Humans ; Young Adult ; Adult ; Glycogen Storage Disease Type I/genetics* ; Gout/genetics* ; Mutation ; Lipids

OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected by glycogen storage disease (GSD) type Ia with gout as the first manifestation. METHODS: Clinical and biochemical data of the pedigree were collected. Available members of the pedigree were subjected to gene sequencing, and the result was analyzed by bioinformatics software. The pedigree was followed up for five years. RESULTS: The proband was a young female manifesting recurrent gout flare, hypoglycemia, and hypertriglyceridemia. One of her younger brothers also presented with dysplasia and hepatic adenoma. Gene sequencing revealed that the proband and her younger brother both harbored c.1022T>A (p.I1e341Asn) and c.230+5G>A compound heterozygous variants of the G6PC gene , which were inherited from their father and mother, respectively. Among these, the c.230+5G>A is an intron region variant which was unreported previously, and bioinformatics analysis showed that it may impact mRNA splicing of the gene. The proband was treated with raw corn starch, allopurinol, and fenofibrate. Gout was well controlled, and she had given birth to a baby girl without GSD. CONCLUSION GSD Ia should be considered among young gout patients with hypoglycemia and hepatomegaly, for which gene sequencing is warranted. GSD Ia has a good prognosis after comprehensive treatment with diet and medicine.
China ; Female ; Glycogen Storage Disease Type I ; Gout/genetics* ; Humans ; Hypoglycemia ; Male ; Pedigree ; Symptom Flare Up

OBJECTIVETo investigate the mutation of glucose-6-phosphatase gene (G6PC gene) in a patient with glycogen storage disease Ⅰa.

METHODSPCR was used to amplify all five exons of G6PC gene. The PCR products were directly sequenced to detect the mutations.

RESULTSA heterozygous 743G>A mutation was found in the patient and his mother, resulting in the substitution of glycine (G) by arginine (R) in codon 222(G222R) in the putative membrane-spanning domain in human G6Pase, but not in his father and his sister.

CONCLUSIONSG222R mutation in G6PC gene was first identified in a patient with glycogen storage disease Ⅰa in mainland China.

Child, Preschool ; Glucose-6-Phosphatase ; genetics ; Glycogen Storage Disease Type I ; genetics ; Humans ; Male ; Mutation ; Sequence Analysis, DNA

Antiporters ; genetics ; Base Sequence ; Female ; Glycogen Storage Disease Type I ; diagnosis ; genetics ; Humans ; Infant ; Monosaccharide Transport Proteins ; genetics ; Mutation ; Polymerase Chain Reaction ; Sequence Analysis, DNA

OBJECTIVEGlycogen storage disease type Ib (GSDIb) is caused by a deficiency of glucose-6-phosphate translocase (G6PT) activity due to SLC37A4 gene mutations. Most GSDIb patients have recurrent infections and inflammatory bowel disease, with poor prognosis. Detection of SLC37A4 gene mutations is of great significance for the diagnosis, subtyping and outcome prediction of GSD patients. This study aims to analyze SLC37A4 gene mutations in Chinese GSDIb patients and to investigate the relationship between its genotypes and clinical manifestations.

METHODSAll exons and their flanking introns of SLC37A4 gene in 28 Chinese children with a primary diagnosis of GSDIb were screened by PCR combined with direct DNA sequencing to detect SLC37A4 gene mutations.

RESULTSFive SLC37A4 gene mutations were detected in 7 (25%) of the 28 children, i.e., p.Gly149Glu (9/13, 69%), p.Gly115Arg (1/13, 8%), p.Pro191Leu (1/13, 8%), c.959-960 insT (1/13, 8%) and c.870+5G>A (1/13, 8%).

CONCLUSIONSIn this study, c.959-960 insT is a novel mutation and p.Gly149Glu is the most common mutation. p.Gly149Glu may be associated with severe infections in children with GSDIb.

Antiporters ; genetics ; Child, Preschool ; Female ; Glycogen Storage Disease Type I ; complications ; genetics ; Humans ; Infant ; Male ; Monosaccharide Transport Proteins ; genetics ; Mutation ; Sequence Analysis, DNA

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

OBJECTIVEGlycogen 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 hyperlipidemia, 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.

METHODData 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, hyperlipidemia 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.

RESULTA 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.

CONCLUSIONA 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.

Adolescent ; Adult ; Antiporters ; genetics ; Child ; Child, Preschool ; DNA Mutational Analysis ; Female ; Genotype ; Glycogen Storage Disease Type I ; genetics ; Humans ; Infant ; Male ; Monosaccharide Transport Proteins ; genetics ; Mutation ; Pedigree ; Young Adult

OBJECTIVETo develop and evaluate a simple, fast and accurate prenatal diagnosis method for glycogen storage disease Ia (GSD Ia) in Chinese.

METHODSThis study involved 3 unrelated families. Genomic DNA samples were extracted from the blood of three GSD Ia patients and their parents, from the amniocytes of 3 fetuses and the blood of 2 newborns. By the way of restriction enzyme analysis, the screening for 727G-->T and R83H mutations of glucose-6-phosphatase gene was carried out in conjunction with 1176 nucleotide polymorphism linkage analysis so as to make the gene and prenatal diagnosis of 3 GSD Ia families. Direct DNA sequencing of the corresponding PCR products was used to confirm the unveiled mutations and 1176 nucleotide polymorphism.

RESULTSThree probands were homozygotes for the 727G-->T mutation and their parents were heterozygotes for this mutation. The fetuses of family 1 and 3 were heterozygotes for the 727G-->T mutation, whereas the fetus of family 2 did not carry this mutation. The 1176 nucleotide polymorphisms of 3 fetuses were different from those of the corresponding probands. The prenatal diagnoses of family 1 and 2 were confirmed by the postnatal biochemical and molecular studies.

CONCLUSIONThese findings suggest that the screening for 727G-->T and R83H mutations in conjunction with the 1176 polymorphism linkage analysis be a simple, fast and accurate method for gene and prenatal diagnosis of GSD Ia in Chinese.

Adult ; Child ; Child, Preschool ; Family Health ; Female ; Genetic Linkage ; Glucose-6-Phosphatase ; genetics ; Glycogen Storage Disease Type I ; diagnosis ; genetics ; Humans ; Male ; Pedigree ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis ; methods

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