Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×10⁹, 0.50×10⁹, 0.48×10⁹, 0.48×10⁹/L to 1.48×10⁹, 3.04×10⁹, 1.10×10⁹, 0.73×10⁹/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.
Humans ; Child ; Child, Preschool ; Adolescent ; Prospective Studies ; Glycogen Storage Disease Type I/drug therapy* ; Neutropenia ; Abdominal Pain ; Diarrhea/drug therapy* ; Hypoglycemia

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

Child ; China ; Consensus ; Glycogen Storage Disease ; Glycogen Storage Disease Type I ; Glycogen Storage Disease Type II ; Glycogen Storage Disease Type III ; Humans

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

Aged ; Aged, 80 and over ; Fatal Outcome ; Female ; Glycogen Storage Disease Type I ; complications ; Hepatitis E ; complications ; Hong Kong ; Humans ; Male ; Middle Aged ; Risk Factors

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

We report a case of 13 years old male patient. He was diagnosed as glycogen storage disease Ib at 6 month age, and received cadaver donor liver transplantation at 2 years and 4 months. He underwent immunosuppression for 9 years with several immunosuppressants including tacrolimus. Then he visited hospital for gum swelling and showed multiple malignancy suspicious lesions at nasal cavity, maxilla, mandibula, frontal bone, temporal bone, C1 and C2 spines, and several submandibular lymph nodes at radiologic study. Biopsy was done at oral cavity lesion, and histologically diagnosed as diffuse large B-cell lymphoma. The tissue specimen showed positivity in Epstein-Barr virus polymerase chain reaction (PCR). After diagnosis, the patient stopped all immunosuppressive agents and received 9 cycles of CHOP (cyclophosphamide, adriamycin, vincristine and prenisolone) chemotherapy for 8 months, then the patient achieved radiologic remission state, and being well without any signs of recurrence for two years of follow up.
Biopsy ; Cadaver ; Child ; Doxorubicin ; Follow-Up Studies ; Frontal Bone ; Gingiva ; Glycogen Storage Disease ; Glycogen Storage Disease Type I ; Herpesvirus 4, Human ; Humans ; Immunosuppression ; Immunosuppressive Agents ; Liver ; Liver Transplantation ; Lymph Nodes ; Lymphoma ; Lymphoma, B-Cell ; Male ; Maxilla ; Mouth ; Nasal Cavity ; Polymerase Chain Reaction ; Recurrence ; Spine ; Tacrolimus ; Temporal Bone ; Tissue Donors ; Transplants ; Vincristine

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