Congenital Hyperinsulinism Of Infancy Research Articles

Deficiency of the metabolic enzyme SCHAD in pancreatic β-cells promotes amino acid–sensitive hypoglycemia

Congenital hyperinsulinism of infancy (CHI) can be caused by a deficiency of the ubiquitously expressed enzyme short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD). To test the hypothesis that SCHAD-CHI arises from a specific defect in pancreatic β-cells, we created genetically engineered β-cell-specific (β-SKO) or hepatocyte-specific (L-SKO) SCHAD knockout mice. While L-SKO mice were normoglycemic, plasma glucose in β-SKO animals was significantly reduced in the random-fed state, after overnight fasting, and following refeeding. The hypoglycemic phenotype was exacerbated when the mice were fed a diet enriched in leucine, glutamine, and alanine. Intraperitoneal injection of these three amino acids led to a rapid elevation in insulin levels in β-SKO mice compared to controls. Consistently, treating isolated β-SKO islets with the amino acid mixture potently enhanced insulin secretion compared to controls in a low-glucose environment. RNA sequencing of β-SKO islets revealed reduced transcription of β-cell identity genes and upregulation of genes involved in oxidative phosphorylation, protein metabolism, and Ca2+ handling. The β-SKO mouse offers a useful model to interrogate the intra-islet heterogeneity of amino acid sensing given the very variable expression levels of SCHAD within different hormonal cells, with high levels in β- and δ-cells and virtually absent α-cell expression. We conclude that the lack of SCHAD protein in β-cells results in a hypoglycemic phenotype characterized by increased sensitivity to amino acid-stimulated insulin secretion and loss of β-cell identity.

Pathological features in non-neoplastic congenital and adult hyperinsulinism: from nesidioblastosis to current terminology and understanding.

Nesidioblastoma and nesidioblastosis were terms given to neoplastic and non-neoplastic lesions of the pancreas associated with pancreatogenous hyperinsulinaemic hypoglycaemia. While nesidioblastoma was rapidly replaced by islet cell tumour, nesidioblastosis, defined as the proliferation of islet cells budding off from pancreatic ducts, was the diagnostic term associated with congenital hyperinsulinism of infancy (CHI) and adult non-neoplastic hyperinsulinaemic hypoglycaemia (ANHH). When it was shown that nesidioblastosis was not specific for CHI or ANHH, it was no longer applied to CHI but kept for the morphological diagnosis of ANHH. In severe CHI cases, a diffuse form with hypertrophic ß-cells in all islets can be distinguished from a focal form with hyperactive ß-cells changes in a limited adenomatoid hyperplastic area. Genetically, mutations were identified in several ß-cell genes involved in insulin secretion. Most common are mutations in the ABCC8 or KCNJ11 genes, solely affected in the diffuse form and associated with a focal maternal allelic loss on 11p15.5 in the focal form. Focal CHI can be localized by 18F-DOPA-PET and is thus curable by targeted resection. Diffuse CHI that fails medical treatment requires subtotal pancreatectomy. In ANHH, an idiopathic form can be distinguished from a form associated with gastric bypass, in whom GLP1-induced stimulation of the ß-cells is discussed. While the ß-cells in idiopathic ANHH are diffusely affected and are either hypertrophic or show only little changes, it is controversial whether there is a ß-cell increase or ß-cell hyperactivity in patients with gastric bypass. Recognizing morphological signs of ß-cell hyperactivity needs a good knowledge of the non-neoplastic endocrine pancreas across all ages.

Case of Insulinoma in a 2-Months-Old Infant

INTRODUCTION: Insulinoma is congenital hyperinsulinism of infancy (CHI). It is a type of functional neuroendocrine tumor (NET) in the pancreas that manifests with persistent hypoglycemia caused by inappropriately high secretion of insulin (hyperinsulinemia). Comprehensive and multidisciplinary management is required for a better outcome. CASE PRESENTATION: A 2-months-old girl came to the Emergency unit Sanglah Hospital, with a chief complaint of seizure. The patient had a low blood glucose level, high fasting insulin, high LDH, computed tomography of the abdomen result showed isodense heterogeneous lesions border in the cauda pancreas with size 1.32 × 1.24 × 1.35 cm. The anatomy-pathological result showed pancreatic neuroendocrine tumor WHO Grade II, functional, consistent, and clinically to insulinoma on the tail of the pancreas. The patient was treated with hydrocortisone, nifedipine, and octreotide. The patient underwent laparotomy partial pancreatectomy. In post-surgery condition, she had good drink tolerance, no episode of recurrent seizure, and blood glucose was controlled. CONCLUSION: Insulinoma is a rare disease. The diagnosis was challenging. This case report presents the diagnostic work-up and management of a patient with a persistent hypoglycemia condition that was diagnosed as insulinoma.

Congenital hyperinsulinism of infancy in a child with autosomal dominant hypocalcaemia type 1 due to an activating calcium sensing receptor mutation

Congenital hyperinsulinism of infancy in a child with autosomal dominant hypocalcaemia type 1 due to an activating calcium sensing receptor mutation

Beta-Cell SCHAD Deficiency Causes Hypoglycemia in Mice

Congenital Hyperinsulinism of Infancy (CHI) is a group of rare, inheritable disorders with persistent hypoglycemia due to hyperinsulinemia. CHI is caused by mutations in genes that affect regulation of insulin secretion in β-cells. One such gene is HADH, which encodes short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD), a metabolic enzyme of the fatty acid beta-oxidation pathway. Mutations resulting in SCHAD deficiency cause protein-sensitive CHI and increased systemic levels of some fatty acid oxidation metabolites. To test the hypothesis that SCHAD-CHI is caused by a specific deficiency of this ubiquitously expressed protein in β-cells we created β-cell-specific SCHAD knock-out (β-SCHADKO) mice by crossing Hadh-floxed animals with mice expressing Cre under the regulation of the Ins1 promoter. Validity of the β-SCHADKO model was confirmed by PCR, Western Blot and immunofluorescence staining of pancreas tissue. Growth and development of β-SCHADKO mice was similar to littermate controls. Plasma glucose in the KOs was significantly reduced in the random fed state (♂ 158 ± 15 vs. 115 ± 28 mg/dL, p=0.0016; ♀ 143 ± 8 vs. 97 ± 19 mg/dL, p<0.0001) and after overnight fasting (♂ 82 ± 14 vs. 56 ± 13 mg/dL, p<0.0002; ♀ 62 ± 7 vs. 42 ± 4 mg/dL, p<0.0001). Insulin and C-peptide levels were elevated in female KOs after overnight fasting (insulin: 0.25 ± 0.15 vs. 0.38 ± 0.21 ng/mL, p=0.0507; C-peptide: 0.15 ± 0.07 vs. 0.26 ± 0.16 ng/mL, p=0.05), but unchanged in the fed state. GSIS and overall glucose homeostasis, as assessed by insulin and glucose tolerance tests, were not significantly altered. Overall, these data indicate that the β-SCHADKO mouse is a suitable model to investigate the hypoglycemic phenotype of underlying SCHAD deficiency. Disclosure J. Ludeke: None. K.M. Velasco: None. D.F. De Jesus: None. B.A. Slipp: None. J. Hu: None. S.J. Steine: None. G. Helgeland: None. P. Njølstad: None. R. Kulkarni: None. A. Molven: None.

The Physiopathological Role of the Exchangers Belonging to the SLC37 Family.

The human SLC37 gene family includes four proteins SLC37A1-4, localized in the endoplasmic reticulum (ER) membrane. They have been grouped into the SLC37 family due to their sequence homology to the bacterial organophosphate/phosphate (Pi) antiporter. SLC37A1-3 are the less characterized isoforms. SLC37A1 and SLC37A2 are Pi-linked glucose-6-phosphate (G6P) antiporters, catalyzing both homologous (Pi/Pi) and heterologous (G6P/Pi) exchanges, whereas SLC37A3 transport properties remain to be clarified. Furthermore, SLC37A1 is highly homologous to the bacterial glycerol 3-phosphate permeases, so it is supposed to transport also glycerol-3-phosphate. The physiological role of SLC37A1-3 is yet to be further investigated. SLC37A1 seems to be required for lipid biosynthesis in cancer cell lines, SLC37A2 has been proposed as a vitamin D and a phospho-progesterone receptor target gene, while mutations in the SLC37A3 gene appear to be associated with congenital hyperinsulinism of infancy. SLC37A4, also known as glucose-6-phosphate translocase (G6PT), transports G6P from the cytoplasm into the ER lumen, working in complex with either glucose-6-phosphatase-α (G6Pase-α) or G6Pase-β to hydrolyze intraluminal G6P to Pi and glucose. G6PT and G6Pase-β are ubiquitously expressed, whereas G6Pase-α is specifically expressed in the liver, kidney and intestine. G6PT/G6Pase-α complex activity regulates fasting blood glucose levels, whereas G6PT/G6Pase-β is required for neutrophil functions. G6PT deficiency is responsible for glycogen storage disease type Ib (GSD-Ib), an autosomal recessive disorder associated with both defective metabolic and myeloid phenotypes. Several kinds of mutations have been identified in the SLC37A4 gene, affecting G6PT function. An increased autoimmunity risk for GSD-Ib patients has also been reported, moreover, SLC37A4 seems to be involved in autophagy.

Laparoscopic Resection of Pancreatic Tumors in Children: Results of a Multicentric Survey.

This study aimed to report the results of a multicentric survey about laparoscopic treatment of pancreatic tumors in children. The data of patients operated using minimally invasive surgery (MIS) for a pancreatic tumor in 5 International centers of Pediatric Surgery in the last 5 years were retrospectively reviewed. We recorded data relating to the clinical presentation, diagnostic evaluation, surgical technique, and outcome. Fifteen patients (average age 2.2 years) were identified. The most common symptoms at presentation were related to the hypoglycemic hyperinsulinism, followed by abdominal pain and vomiting. Tumor types were insulinoma (n = 4), congenital hyperinsulinism of infancy (CHI) diffuse type (n = 3), CHI focal type (n = 3), solid pseudopapillary tumor (n = 2), and cystic malformation (n = 3). The diagnostic assessment was completed using ultrasound associated with computed tomography (CT) scan in all centers; 18FDOPA positron emission tomography in combination with CT was adopted in 2 centers. The MIS procedures performed were as follows: tumor enucleation (n = 4), distal pancreatectomy (n = 8), subtotal pancreatectomy (n = 2), and pancreatico-jejunostomy (n = 1). Average operative time was 110 minutes. As for postoperative complications, we recorded 1 persistent hypoglycemia, requiring redo-surgery (IIIb Clavien-Dindo) and 1 thrombosis of splenic vein, not requiring any treatment (I Clavien-Dindo). Laparoscopic resection can be considered a safe and effective treatment with minimal morbidity and excellent outcomes for most pediatric pancreatic tumors. Suspension of the stomach with a transparietal stitch and use of new hemostatic devices as Starion TLS3 or Ligasure are key factors for the success of the procedure. A long-term follow-up is mandatory in these patients to evaluate postoperative complications and long-term outcome.

Ketotic hypoglycaemia in children with transient congenital hyperinsulinism of infancy

Ketotic hypoglycaemia in children with transient congenital hyperinsulinism of infancy

The Hypoglycemic Phenotype Is Islet Cell-Autonomous in Short-Chain Hydroxyacyl-CoA Dehydrogenase-Deficient Mice.

Congenital hyperinsulinism of infancy (CHI) can be caused by inactivating mutations in the gene encoding short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD), a ubiquitously expressed enzyme involved in fatty acid oxidation. The hypersecretion of insulin may be explained by a loss of interaction between SCHAD and glutamate dehydrogenase in the pancreatic β-cells. However, there is also a general accumulation of metabolites specific for the enzymatic defect in affected individuals. It remains to be explored whether hypoglycemia in SCHAD CHI can be uncoupled from the systemic effect on fatty acid oxidation. We therefore transplanted islets from global SCHAD knockout (SCHADKO) mice into mice with streptozotocin-induced diabetes. After transplantation, SCHADKO islet recipients exhibited significantly lower random and fasting blood glucose compared with mice transplanted with normal islets or nondiabetic, nontransplanted controls. Furthermore, intraperitoneal glucose tolerance was improved in animals receiving SCHADKO islets compared with those receiving normal islets. Graft β-cell proliferation and apoptosis rates were similar in the two transplantation groups. We conclude that hypoglycemia in SCHAD-CHI is islet cell–autonomous.

High Incidence of Heterozygous ABCC8 and HNF1A Mutations in Czech Patients With Congenital Hyperinsulinism.

Congenital hyperinsulinism of infancy (CHI) represents a group of heterogeneous disorders characterized by oversecretion of insulin from pancreatic β-cells causing severe hypoglycemia. We studied the distribution of genetic causes of CHI in a Czech population. Countrywide collection of patients with CHI included 40 subjects (12 females, median age of diagnosis, 1 wk [interquartile range, 1-612 wk]). We sequenced the ABCC8, KCNJ11, GLUD1, GCK, HADH, UCP2, SLC16A1, HNF4A, and HNF1A genes and investigated structural changes in the ABCC8 gene. We functionally tested novel variants in the ABCC8 gene by Rb(86+) efflux assay and novel variants in the HNF1A gene by transcriptional activation and DNA-binding tests. We found causal mutations in 20 subjects (50%): 19 carried a heterozygous mutation while one patient was homozygous for mutation in the ABCC8 gene. Specifically, we detected 11 mutations (seven novel) in ABCC8, one novel mutation in KCNJ11, five mutations (two novel) in HNF1A, two novel mutations in HNF4A, and one in GCK. We showed a decrease of activation by diazoxide in mutant KATP channels with novel ABCC8 variants by 41-91% (median, 82%) compared with wild-type (WT) channels and reduced transcriptional activity of mutant HNF1A proteins (2.9% for p.Asn62Lysfs93* and 22% for p.Leu254Gln) accompanied by no DNA-binding ability compared with WT HNF1A. We detected a higher proportion of heterozygous mutations causing CHI compared with other cohorts probably due to lack of consanguinity and inclusion of milder CHI forms. Interestingly, HNF1A gene mutations represented the second most frequent genetic cause of CHI in the Czech Republic. Based on our results we present a genetic testing strategy specific for similar populations.

Congenital hyperinsulinism in Polish patients--how can we optimize clinical management?

Congenital hyperinsulinism of Infancy (CHI) comprises heterogenic defects of insulin secretion with diverse molecular aetiology, histological features, severity of symptoms, and response to pharmacotherapy. The study aimed to establish the first clinical characteristics of Polish patients with CHI and to propose a novel clinical algorithm allowing the prioritisation of genetic and radiology studies, based on patient's characteristics and response to pharmacotherapy. Thirty-one patients with CHI were recruited from five reference centres in Poland. Clinical and biochemical parameters were statistically evaluated and compared to those of a control group (n = 30). CHI predisposes to increased birth weight (p = 0.004), lower Apgar score (p = 0.004), perinatal complications (74%), and neurological implications (48%). Diagnostic process and therapy were inconsistent. A trial of pharmacotherapy was applied in 21 patients (68%), and diagnostic imaging with 18F-L-DOPA PET was performed in only 3. Eighteen patients (58%) were surgically treated, including 8 infants (44%) aged less than 2 months. Depending on the type of resection, further hypoglycaemia was observed postoperatively in 50% (n = 9) and hyperglycaemia in 39% (n = 7) of cases. Based on foregoing results, a clinical algorithm was proposed. Standardisation of clinical management with the use of pharmacotherapy, genetic screening, and diagnostic imaging will allow the optimisation of therapy and minimisation of treatment complications.

Whole Genome SNP Genotyping and Exome Sequencing Reveal Novel Genetic Variants and Putative Causative Genes in Congenital Hyperinsulinism

Congenital hyperinsulinism of infancy (CHI) is a rare disorder characterized by severe hypoglycemia due to inappropriate insulin secretion. The genetic causes of CHI have been found in genes regulating insulin secretion from pancreatic β-cells; recessive inactivating mutations in the ABCC8 and KCNJ11 genes represent the most common events. Despite the advances in understanding the molecular pathogenesis of CHI, specific genetic determinants in about 50 % of the CHI patients remain unknown, suggesting additional locus heterogeneity. In order to search for novel loci contributing to the pathogenesis of CHI, we combined a family-based association study, using the transmission disequilibrium test on 17 CHI patients lacking mutations in ABCC8/KCNJ11, with a whole-exome sequencing analysis performed on 10 probands. This strategy allowed the identification of the potential causative mutations in genes implicated in the regulation of insulin secretion such as transmembrane proteins (CACNA1A, KCNH6, KCNJ10, NOTCH2, RYR3, SCN8A, TRPV3, TRPC5), cytosolic (ACACB, CAMK2D, CDKAL1, GNAS, NOS2, PDE4C, PIK3R3) and mitochondrial enzymes (PC, SLC24A6), and in four genes (CSMD1, SLC37A3, SULF1, TLL1) suggested by TDT family-based association study. Moreover, the exome-sequencing approach resulted to be an efficient diagnostic tool for CHI, allowing the identification of mutations in three causative CHI genes (ABCC8, GLUD1, and HNF1A) in four out of 10 patients. Overall, the present study should be considered as a starting point to design further investigations: our results might indeed contribute to meta-analysis studies, aimed at the identification/confirmation of novel causative or modifier genes.

Genetic Analysis of Italian Patients with Congenital Hyperinsulinism of Infancy

Background/Aims: Congenital hyperinsulinism of infancy is a rare disease that needs prompt treatment to avoid brain damage. There are currently no data regarding the clinical and molecular features of Italian patients. Methods: Thirty-three patients with HI and their parents were included. Consanguinity was reported in six patients. Half of patients were macrosomic at birth. None had raised 3-hydroxybutyrylcarnitine or hyperammonemia. Molecular analysis of ABCC8 and KCNJ11 genes was performed in all patients, and subjects with no mutation underwent analysis of HNF4A and GCK. GLUD1 and HADH genes were analyzed in a patient with leucine sensitivity. Results: Mutations in the ABCC8 and KCNJ11 genes were found in 45% of the patients (6 novel). No mutations in HNF4A, GLUD1 and GCK genes were found. Recessive mode of inheritance was found in 21% of patients. A single heterozygous mutation was identified in 24% of probands. 72% of the patients were responsive to medical treatment, and 44% of the 17 patients with no identified mutation achieved spontaneous remission. Nine children, unresponsive to medical therapy, underwent pancreatectomy. Conclusion: This is the first report on hyperinsulinism of infancy in Italy, confirming the complexity of the clinical forms and the heterogeneity of the genetic causes of the disease.

Pancreatic head resection preserving the main pancreatic duct for congenital hyperinsulinism of infancy

Surgical intervention for congenital hyperinsulinism with an unclear focal lesion in the pancreatic head sometimes require the resection of most of the pancreas head and pancreaticojejunotomy. This report presents the case of a patient that underwent pancreatic head resection preserving the main pancreatic duct to avoid pancreaticojejunostomy.

Cardiac abnormalities in children with congenital hyperinsulinism [CHI

Congenital hyperinsulinism of Infancy (CHI) can be associated with cardiac problems such as septal hypertrophy and reversible hypertrophic cardiomyopathy1 2 however, the prevalence and range of cardiac abnormalities in CHI...

In vitro recovery of ATP-sensitive potassium channels in β-cells from patients with congenital hyperinsulinism of infancy.

OBJECTIVECongenital hyperinsulinism in infancy (CHI) is characterized by unregulated insulin secretion from pancreatic β-cells; severe forms are associated with defects in ABCC8 and KCNJ11 genes encoding sulfonylurea receptor 1 (SUR1) and Kir6.2 subunits, which form ATP-sensitive K+ (KATP) channels in β-cells. Diazoxide therapy often fails in the treatment of CHI and may be a result of reduced cell surface expression of KATP channels. We hypothesized that conditions known to facilitate trafficking of cystic fibrosis transmembrane regulator (CFTR) and other proteins in recombinant expression systems might increase surface expression of KATP channels in native CHI β-cells.RESEARCH DESIGN AND METHODSTissue was isolated during pancreatectomy from eight patients with CHI and from adult cadaver organ donors. Patients were screened for mutations in ABCC8 and KCNJ11. Isolated β-cells were maintained at 37°C or 25°C and in the presence of 1) phorbol myristic acid, forskolin and 3-isobutyl-1-methylxanthine, 2) BPDZ 154, or 3) 4-phenylbutyrate. Surface expression of functional channels was assessed by patch-clamp electrophysiology.RESULTSMutations in ABCC8 were detected for all patients tested (n = 7/8) and included three novel mutations. In five of eight patients, no changes in KATP channel activity were observed under different cell culture conditions. However, in three patients, in vitro recovery of functional KATP channels occurred. Here, we report the first cases of recovery of defective KATP channels in human β-cells using modified cell culture conditions.CONCLUSIONSOur study establishes the principle that chemical modification of KATP channel subunit trafficking could be of benefit for the future treatment of CHI.

The predictive value of preoperative fluorine-18- l-3,4-dihydroxyphenylalanine positron emission tomography –computed tomography scans in children with congenital hyperinsulinism of infancy

Background/Purpose In congenital hyperinsulinism (CHI) of infancy, the use of preoperative fluorine-18- l-3,4-dihydroxyphenylalanine–positron emission tomography–computed tomography ( 18F-DOPA-PET-CT) scan has recently been reported. The aim of this study was to evaluate the accuracy of this technique in discriminating between diffuse and focal CHI and the anatomical localization of focal lesions. Methods Between 2006 and 2010, 18F-DOPA-PET scan was performed in 19 children with CHI (median age, 2 months; range, 1-12 months) who were not responding to medical therapy and underwent laparoscopic or open surgery. The findings of 18F-DOPA-PET scan were correlated with histology. Results In 5 children, 18F-DOPA-PET scan showed diffuse pancreatic uptake, confirmed at histology and supporting the genetic suspicion of diffuse disease. In 14 children, 18F-DOPA-PET scan indicated focal pancreatic uptake, which corresponded to histology. However, in 5 patients (36%), 18F-DOPA-PET scan was inaccurate in defining the location of the lesion (n = 3), size of the lesion (n = 1), or both location and size (n = 1), leading to an inaccurate pancreatic resection. Conclusions Fluorine-18- l-3,4-dihydroxyphenylalanine–positron emission tomography–computed tomography scan discriminates between diffuse and focal forms of CHI. In focal forms, 18F-DOPA-PET scan is useful in 2/3 of patients in defining the site and dimension of the focal lesion. Intraoperative histologic confirmation of complete focal lesion resection is needed.

Surgical management of congenital hyperinsulinism of infancy

Congenital hyperinsulinism of infancy (CHI) is characterized by inappropriate insulin secretion resulting in persistent hypoglycemia, which can lead to irreversible severe neurological damage in the infant. Many patients with CHI will respond to medical therapy, but surgery is necessary in those that do not. There are 2 main histologic subtypes, diffuse and focal, both of which may require different surgical strategies. Near-total pancreatectomy is the procedure of choice for diffuse CHI, whereas a localized resection is curative in focal CHI. Open surgery is the traditional approach to pancreatic resection. However, laparoscopy is increasingly used, particularly in localized resection for focal disease. We describe both methods of pancreatectomy.

A mutation in KCNJ11 causing human hyperinsulinism (Y12X) results in a glucose-intolerant phenotype in the mouse

We identified a mouse with a point mutation (Y12STOP) in the Kcnj11 subunit of the K(ATP) channel. This point mutation is identical to that found in a patient with congenital hyperinsulinism of infancy (HI). We aimed to characterise the phenotype arising from this loss-of-function mutation and to compare it with that of other mouse models and patients with HI. We phenotyped an N-ethyl-N-nitrosourea-induced mutation on a C3H/HeH background (Kcnj11 ( Y12STOP )) using intraperitoneal glucose tolerance testing to measure glucose and insulin plasma concentrations. Insulin secretion and response to incretins were measured on isolated islets. Homozygous male and female adult Kcnj11 ( Y12STOP ) mice exhibited impaired glucose tolerance and a defect in insulin secretion as measured in vivo and in vitro. Islets had an impaired incretin response and reduced insulin content. The phenotype of homozygous Kcnj11 ( Y12STOP ) mice is consistent with that of other Kcnj11-knockout mouse models. In contrast to the patient carrying this mutation homozygously, the mice studied did not have hyperinsulinaemia or hypoglycaemia. It has been reported that HI patients may develop diabetes and our mouse model may reflect this clinical feature. The Kcnj11 ( Y12STOP ) model may thus be useful in further studies of K(ATP) channel function in various cell types and in investigation of the development of hyperglycaemia in HI patients.

An Egyptian case of congenital hyperinsulinism of infancy due to a novel mutation in KCNJ11 encoding Kir6.2 and response to octreotide

Congenital hyperinsulinism of infancy (CHI) is a rare heterogeneous disease mostly attributable to mutations in the genes encoding the KATP channel subunits found in pancreatic β-cells. Here, we report a child presenting at day 1 with persistent hyperinsulinemic hypoglycemia and who underwent open laparotomy and subtotal pancreatectomy with resection of tail and body of pancreas at 30days of age. Normoglycemia was restored by Octreotide that was discontinued when the child was 7-month old. However, 3months later Octreotide was re-administered as hypoglycemic attacks recurred. On follow-up, the child has adequate glycemic control and is thriving well with no neurodevelopmental morbidity. Genetic analysis revealed the novel mutation c.407G>A [p.R136H] in KCNJ11 encoding Kir6.2, confirming the diffuse form of CHI. This is to our knowledge the first reported Egyptian case of CHI due to a mutation in KCNJ11.