Persistent hyperinsulinemic hypoglycemia of infancy due to homozygous KCNJ11 (T294M) mutation

Ilamaran, V.; Chandrasekaran, Venkatesh; K, Manish; Adhisivam, B

doi:10.1007/s12098-010-0100-7

Cited by 3 publications

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References 4 publications

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“…In the 14 mutations, a missense mutation (Thr294Met in KCNJ11 ) was reported previously in Indians and Europeans [25,26]. 13 mutations, including 7 missense mutations, 5 nonsense mutations and 1 frameshift mutation were in the ABCC8 gene.…”

Section: Resultsmentioning

confidence: 90%

Long-Term Follow-Up and Mutation Analysis of 27 Chinese Cases of Congenital Hyperinsulinism

Gong

Sanger

et al. 2014

Horm Res Paediatr

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Objectives: Long-term clinical follow-up and mutation analysis were performed in 27 Chinese congenital hyperinsulinism patients. Method: 27 hypoglycemia patients were diagnosed with CHI within 2 years of age. The long-term clinical outcome was analyzed and mutation analysis of 5 hyperinsulinism candidate genes was performed. Results: The median onset age of hypoglycemia in the patients was 60 days; 11 patients showed hypoglycemic symptoms in the neonatal stage, and hypoglycemia in most of the patients was first expressed as a seizure. Blood was collected during the hypoglycemic episode and insulin levels were significantly elevated. ABCC8, KCNJ11, GCK, HNF4a and GLUD1 genes were screened for mutation analysis. 14 mutations in ABCC8 or KCNJ11 genes in 12 cases were identified (44%). 57% (8/14) of the mutations have not been reported before. 83% (10/12) of the patients have a monoallelic mutation. 58% of these 12 patients were predicted to be focal. 73% of the patients without KATP channel mutations were sensitive to diazoxide. 26 patients were followed over a period of 1-13 years. 50% of all 27 patients showed brain impairment. Conclusions: Chinese CHI patients are similar to other ethnic groups in terms of prevalence of KATP-HI, onset age, severity of hypoglycemia and treatment. Mutations in ABCC8 and KCNJ11 are common causes of CHI in Chinese patients. Mutation analysis showed more novel and monoallele mutations in KATP genes.

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Section: Resultsmentioning

confidence: 90%

Long-Term Follow-Up and Mutation Analysis of 27 Chinese Cases of Congenital Hyperinsulinism

Gong

Sanger

et al. 2014

Horm Res Paediatr

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Conservatively treated Congenital Hyperinsulinism (CHI) due to K-ATP channel gene mutations: reducing severity over time

Salomon‐Estebanez

Flanagan

Ellard

et al. 2016

Orphanet J Rare Dis

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BackgroundPatients with Congenital Hyperinsulinism (CHI) due to mutations in K-ATP channel genes (K-ATP CHI) are increasingly treated by conservative medical therapy without pancreatic surgery. However, the natural history of medically treated K-ATP CHI has not been described; it is unclear if the severity of recessively and dominantly inherited K-ATP CHI reduces over time. We aimed to review variation in severity and outcomes in patients with K-ATP CHI treated by medical therapy.MethodsTwenty-one consecutively presenting patients with K-ATP CHI with dominantly and recessively inherited mutations in ABCC8/KCNJ11 were selected in a specialised CHI treatment centre to review treatment outcomes. Medical treatment included diazoxide and somatostatin receptor agonists (SSRA), octreotide and somatuline autogel. CHI severity was assessed by glucose infusion rate (GIR), medication dosage and tendency to resolution. CHI outcome was assessed by glycaemic profile, fasting tolerance and neurodevelopment.ResultsCHI presenting at median (range) age 1 (1, 240) days resolved in 15 (71%) patients at age 3.1(0.2, 13.0) years. Resolution was achieved both in patients responsive to diazoxide (n = 8, 57%) and patients responsive to SSRA (n = 7, 100%) with earlier resolution in the former [1.6 (0.2, 13.0) v 5.9 (1.6, 9.0) years, p = 0.08]. In 6 patients remaining on treatment, diazoxide dose was reduced in follow up [10.0 (8.5, 15.0) to 5.4 (0.5, 10.8) mg/kg/day, p = 0.003]. GIR at presentation did not correlate with resolved or persistent CHI [14.9 (10.0, 18.5) v 16.5 (13.0, 20.0) mg/kg/min, p = 0.6]. The type of gene mutation did not predict persistence; resolution could be achieved in recessively-inherited CHI with homozygous (n = 3), compound heterozygous (n = 2) and paternal mutations causing focal CHI (n = 2). Mild developmental delay was present in 8 (38%) patients; adaptive functioning assessed by Vineland Adaptive Behavior Scales questionnaire showed a trend towards higher standard deviation scores (SDS) in resolved than persistent CHI [−0.1 (−1.2, 1.6) v −1.2 (−1.7, 0.03), p = 0.1].ConclusionsIn K-ATP CHI patients managed by medical treatment only, severity is reduced over time in the majority, including those with compound heterozygous and homozygous mutations in ABCC8/KCNJ11. Severity and treatment requirement should be assessed periodically in all children with K-ATP CHI on medical therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0547-3) contains supplementary material, which is available to authorized users.

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Pharmacogenetics of insulin secretagogue antidiabetics

Winkler

Gerö

2011

Orvosi Hetilap

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Type 2 diabetes is making up to 90% of the all diabetic cases. In addition to insulin resistance, insufficient B-cell function also plays an important role in the pathogenesis of the disease. The insufficient production and secretion of insulin can be increased by secretagogue drugs, like sulfonylureas and incretin mimetics/enhancers. In recent years growing number of genetic failures of the B-cells has been detected. These genetic variants can influence the efficacy of secretagogue drugs. Some of these gene polymorphisms were identified in the genes encoding the KATP channel (KCNJ11 and ABCC8). These mutations are able either to reduce or increase the insulin secretion and can modify the insulin response to sulfonylurea treatment. Other polymorphisms were found on genes encoding enzymes or transcription factors. In recent years, the genetic variants of TCF7L2 and its clinical importance have been intensely studied. Authors give a summary of the above gene polymorphisms and their role in insulin secretion.

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Persistent hyperinsulinemic hypoglycemia of infancy due to homozygous KCNJ11 (T294M) mutation

Cited by 3 publications

References 4 publications

Long-Term Follow-Up and Mutation Analysis of 27 Chinese Cases of Congenital Hyperinsulinism

Long-Term Follow-Up and Mutation Analysis of 27 Chinese Cases of Congenital Hyperinsulinism

Conservatively treated Congenital Hyperinsulinism (CHI) due to K-ATP channel gene mutations: reducing severity over time

Pharmacogenetics of insulin secretagogue antidiabetics

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