الملخص
Objective:To investigate the clinical characteristics and gene sequencing results of NDM, so as to provide evidence for clinical diagnosis and treatment .Methods:Clinical data of 1 child diagnosed with NDM in Hebei People's Hospital in January 2021 were retrospectively analyzed, and DNA gene sequencing was performed in the peripheral blood of the child, and relevant literatures were reviewed.Results:The child was born with a weight of 2.2kg. On the second day after birth, blood glucose significantly increased and insulin and C-peptide levels decreased. After 14 days of insulin treatment, hyperglycemia was still present, which was consistent with the diagnosis of NDM. Genetic testing indicated that there were missense mutations of newborn compound heterozygote in ABCC8 gene: c. 752G > A (p.G251E), c. 772A > G (p.R258G). The mutation of c. 772A > G in ABCC8 gene had not been reported before, and sulfonylureas were effective for the treatment of the child.Conclusion:NDM is a rare monogenic genetic disease with a lack of specificity in clinical manifestations. For children diagnosed or suspected of NDM, genetic testing should be actively carried out, which is of great significance for clinical diagnosis, treatment and prognosis.
الملخص
Background: There is limited data from India regarding medical management of congenital hyperinsulinism (CHI). Objective: To study the molecular diagnosis, medical management and outcomes of children with CHI. Study design: Ambispective. Participants: Children with CHI admitted in from December, 2011 till March, 2020 at a tertiary care referral hospital. Outcomes: Clinical and genetic profile, treatment, and response Results: 42 children with a median age of 3 days (range 1 day to 6 years) were enrolled, of which 23 (54.7%) were diazoxideresponsive. Mutations were identified in 28 out of 41 (68.2%) patients. The commonest gene affected was ABCC8 in 22 patients. The pathogenic variant c.331G>A in ABCC8 gene was identified in 6 unrelated cases from one community. Good response to daily octreotide was seen in 13 of the 19 (68.4%) diazoxide-unresponsive patients. Monthly long-acting octreotide was initiated and daily octreotide could be stopped or tapered in 9 patients. Sirolimus was tried with variable response in 6 patients but was discontinued in 5 due to adverse effects. Four patients had focal CHI, of which one underwent partial pancreatic resection. The disease severity reduced with age and neurodevelopment was good in the patients with identifiable genetic defects who were optimally managed. Conclusions: Medical management of CHI is effective, if compliance can be ensured, with good quality of life and neurological outcomes.
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Objective To analyze the clinical characteristics and gene mutations of 56 patients with congenital hyperinsulinism(CHI)and to provide a theoretical basis for clinical diagnosis and treatment of CHI.Methods Fifty-six children who were diagnosed as CHI between February 2002 and January 2016 in Beijing Children's Hospital Affiliated to Capital Medical University were selected as research subjects.A retrospective study was done about the clinical data and the treatment procedures of the 56 patients,such as perinatal conditions,clinical manifestations,laboratory data,treatments,prognosis and so on.Polymerase chain reaction(PCR)-DNA technology or next-generation sequencing technology was used to analyze the CHI relevant genes of the 56 patients.Results Thirty of the 56 patients carried CHI gene mutation.(1)Twenty-three of 56 patients(41.0％)carried ABCC8/KCNJ11 gene mutations:4 of 23 patients carried complex heterozygous mutation,1 of 23 patients carried both ABCC8 and KCNJ11 gene mutation,1 of 23 patients carried maternally inherited ABCC8 gene mutation,12 of 23 patients carried paternally inherited ABCC8 gene mutation,1 of 23 patients carried paternally inherited KCNJ11 gene mutation,3 of 23 patients carried de novo ABCC8 gene mutation,1 of 23 patients had unknown genetic way,19 of 23 patients were treated with Diazoxide,2 of 19 patients were responsive to Diazoxide,7 of 19 patients were unresponsive to Diazoxide and 10 of 19 patients were uncertain to Diazoxide.(2)Five of 56 patients(8.9％)carried GLUD1 gene mutation,4 of 5 patients were treated with Diazoxide and they were all responsive to Diazoxide.(3)One of 56 patients(1.7％)carried de novo GCK gene mutation,responsive to Diazoxide treatment.(4)One of 56 patients(1.7％)carried maternally inherited SLC16A1 gene mutation,responsive to Diazo-xide treatment.Conclusions The ABCC8 gene and GLUD1 gene mutation are the main causative genes of CHI.The GCK gene and SLC16A1 gene mutation are in the minority.Most ABCC8 gene and KCNJ11 gene mutation are unresponsive to Diazoxide treatment.
الملخص
BACKGROUND: The ABCC8 gene which encodes the sulfonylurea receptor plays a major role in insulin secretion and is a potential candidate for type 2 diabetes. The ‑3c → t (rs1799854) and Thr759Thr (C → T, rs1801261) single nucleotide polymorphisms (SNPs) of the ABCC8 gene have been associated with type 2 diabetes in many populations. The present study was designed to investigate the association of these two SNPs in an Asian Indian population from south India. MATERIALS AND METHODS: A total of 1,300 subjects, 663 normal glucose tolerant (NGT) and 637 type 2 diabetic subjects were randomly selected from the Chennai Urban Rural Epidemiology Study (CURES). The ‑3c → t and Thr759Thr were genotyped in these subjects using polymerase chain reaction‑restriction fragment length polymorphism (PCR‑RFLP) and a few variants were confirmed by direct sequencing. RESULTS: The frequency of the ‘t’ allele of the ‑3c → t SNP was found to be 0.27 in NGT and 0.29 in type 2 diabetic subjects (P = 0.44). There was no significant difference in the genotypic frequency between the NGT and type 2 diabetic group (P = 0.18). Neither the genotypic frequency nor the allele frequency of the Thr759Thr polymorphism was found to differ significantly between the NGT and type 2 diabetic groups. CONCLUSION: The ‑3c → t and the Thr759Thr polymorphisms of the ABCC8 gene were not associated with type 2 diabetes in this study. However, an effect of these genetic variants on specific unidentified sub groups of type 2 diabetes cannot be excluded.
الموضوعات
ATP-Binding Cassette Transporters/genetics , Diabetes Mellitus, Type 2/genetics , Genetic Variation , Humans , India , Sulfonylurea Receptors/geneticsالملخص
ABCC8,KCNJ11,and GLUD1 gene mutations were investigated in a male patient with congenital hyperinsulinism and his parents were also investigated.A 1484 G＞A mutation was found in the 10th exon of ABCC8 gene in the patient,which leads to amino acid substitution at the 495 residue of the sulphonylurea receptor SUR1 protein.The patient's father also carried the same heterozygous inactive mutation,while the genotype of the mother was normal,indicating that the gene mutation of the patient was paternally inherited.According to that mutation,it is deduced that the patient may suffer from the focal type of congenital hyperinsulinism.
الملخص
Congenital hyperinsulinism is the most frequent cause of severe, persistent hypoglycemia in infancy and childhood. We report a 2.5 year old girl with severe congenital hyperinsulinism. Mutation analysis showed that the child is a compound heterozygote for two missense mutations in the ABCC8 gene.
الملخص
Fourteen neonatal diabetes mellitus(NDM)patients were recruited. 9 patients were treated with glyburide and the other 5 with insulin. ABCC8, KCNJ11, and INS genes were sequenced in 6 of them. Gene mutations were found in 2, 1, and 1 cases in these genes, respectively. One case with 6q24 hypomethylation and another without known mutation were also found. 8 out of 9 patients treated with glyburide reached euglycemia(88.9%). The other 5 patients with insulin therapy either died or lost contact. The results suggest that glyburide therapy is effective in neonatal diabetes mellitus, while insulin therapy may contribute to poor compliance.