Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism
Open accessAbstract
Background: Congenital hyperinsulinism (CHI) is a clinically heterogeneous condition. Mutations in eight genes (ABCC8,KCNJ11,GLUD1,GCK,HADH,SLC16A1,HNF4A and HNF1A) are known to cause CHI. Aim: To characterise the clinical and molecular aspects of a large cohort of patients with CHI. Methodology: Three hundred patients were recruited and clinical information was collected before genotyping.ABCC8 and KCNJ11 genes were analysed in all patients. Mutations in GLUD1,HADH,GCK and HNF4A genes were sought in patients with diazoxide-responsive CHI with hyperammonaemia (GLUD1), raised 3-hydroxybutyrylcarnitine and/or consanguinity (HADH), positive family history (GCK) or when CHI was diagnosed within the first week of life (HNF4A). Results: Mutations were identified in 136/300 patients (45.3%). Mutations in ABCC8/KCNJ11 were the commonest genetic cause identified (n=109, 36.3%). Among diazoxide-unresponsive patients (n=105), mutations in ABCC8/KCNJ11 were identified in 92 (87.6%) patients, of whom 63 patients had recessively inherited mutations while four patients had dominantly inherited mutations. A paternal mutation in the ABCC8/KCNJ11 genes was identified in 23 diazoxide-unresponsive patients, of whom six had diffuse disease. Among the diazoxide-responsive patients (n=183), mutations were identified in 41 patients (22.4%). These include mutations in ABCC8/KCNJ11(n=15),HNF4A(n=7),GLUD1(n=16) and HADH(n=3). Conclusions: A genetic diagnosis was made for 45.3% of patients in this large series. Mutations in the ABCC8 gene were the commonest identifiable cause. The vast majority of patients with diazoxide-responsive CHI (77.6%) had no identifiable mutations, suggesting other genetic and/or environmental mechanisms.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A rare pathogenic variant in ABCC8 that causes congenital hyperinsulinism was incorrectly genotyped as homozygous in 43% (9/21) of Personal Genome Project individuals.
“A rare pathogenic variant in ABCC8 that causes congenital hyperinsulinism was incorrectly genotyped as homozygous in 43% (9/21) of individuals.”
From Use of SNP chips to detect rare pathogenic variants: retrospective, population based diagnostic evaluation (2021) · cites this paper as [29]
The Results section, “Analysis of ABCC8 gene mutations” (page unavailable), identifies ABCC8 mutations in patients with congenital hyperinsulinism. It does not report that 9 of 21 individuals were incorrectly genotyped as homozygous, or examine Personal Genome Project individuals; that central part of the claim is unsupported. (LLM, conf=0.85)
Experimental — accuracy not yet measuredA rare pathogenic variant in ABCC8 that causes congenital hyperinsulinism is incorrectly genotyped in 43% (9/21) of PGP individuals.
“A rare pathogenic variant in ABCC8 that causes congenital hyperinsulinism [29] is incorrectly genotyped in 43% (9/21) of individuals.”
From Assessing the analytical validity of SNP-chips for detecting very rare pathogenic variants: implications for direct-to-consumer genetic testing (2019) · cites this paper as [29]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Thomas, P. M., Cote, G. J., Wohllk, N., Haddad, B., Mathew, P. M., Rabl, W., Aguilar-Bryan, L., Gagel, R. F., & Bryan, J. (1995) · Science · doi:10.1126/science.7716548 · Cited by 806 · see citing works
Molecular Biology of Adenosine Triphosphate-Sensitive Potassium Channels
Aguilar‐Bryan, L., & Bryan, J. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.2.0361 · Cited by 697 · see citing works
Adenosine Diphosphate as an Intracellular Regulator of Insulin Secretion
Nichols, C. G., Shyng, S., Nestorowicz, A., Gläser, B., Clement, J. P., González, G., Aguilar‐Bryan, L., Permutt, M. A., & Bryan, J. (1996) · Science · doi:10.1126/science.272.5269.1785 · Cited by 525 · see citing works
Thomas, P. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.11.1809 · Cited by 443 · see citing works
Pearson, E. R., Boj, S. F., Steele, A. M., Barrett, T. G., Stals, K. L., Hamilton-Shield, J. P., Ellard, S., Ferrer, J. P., & Hattersley, A. T. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040118 · Cited by 430 · see citing works
Self-citationClayton, P. T., Eaton, S. D., Aynsley-Green, A., Edginton, M., Hussain, K., Krywawych, S., Datta, V., Malingré, H. E. M., Berger, R., & van den Berg, I. E. T. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200111294 · Cited by 311 · see citing works
Self-citationClinical features of 52 neonates with hyperinsulinism.
de Lonlay-Debeney, P., Poggi-Travert, F., Fournet, J., Sempoux, C., Vici, C., Brunelle, F., Touati, G., Rahier, J., Junien, C., Nihoul-Fékété, C., et al. (1999) · New England Journal of Medicine · doi:10.1056/nejm199904153401505 · Cited by 306 · see citing works
Practical management of hyperinsulinism in infancy
Aynsley-Green, A., Hussain, K., Hall, J., Saudubray, J., Nihoul‐Feketé, C., de Lonlay, P., Brunelle, F., Otonkoski, T., Thornton, P., & Lindley, K. J. (2000) · Archives of Disease in Childhood Fetal & Neonatal · doi:10.1136/fn.82.2.f98 · Cited by 298 · see citing works
Self-citationVerkarre, V., Fournet, J., de Lonlay, P., Gross, M., Devillers, M., Rahier, J., Brunelle, F., Robert, J., Nihoul‐Feketé, C., Saudubray, J., et al. (1998) · Journal of Clinical Investigation · doi:10.1172/jci4495 · Cited by 289 · see citing works
Regulation of KATP Channel Activity by Diazoxide and MgADP
Shyng, S.-L., Ferrigni, T., & Nichols, C. G. (1997) · The Journal of General Physiology · doi:10.1085/jgp.110.6.643 · Cited by 282 · see citing works
Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1
Huopio, H., Reimann, F. M., Ashfield, R., Komulainen, J., Lenko, H. L., Rahier, J., Vauhkonen, I., Kere, J., Laakso, M., Ashcroft, F. M., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9804 · Cited by 277 · cited 1× · see citing works
“The phenotype associated with these dominantly inherited mutations confirms the reported phenotype associated with dominant mutations in the NBD2 area (13, 43); however, dominant CHI mutations also occur outside the NBD2 (44).”
Otonkoski, T., Näntö‐Salonen, K., Seppänen, M., Veijola, R., Huopio, H., Hussain, K., Tapanainen, P. J., Eskola, O., Parkkola, R. K., Ekström, K., et al. (2006) · Diabetes · doi:10.2337/diabetes.55.01.06.db05-1128 · Cited by 268 · cited 1× · see citing works
“Using 18F-L -DOPA-PET/CT, it is now possible to pre-operatively localise the focal lesion (31).”
Self-citationNestorowicz, A. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.11.1813 · Cited by 245 · see citing works
Otonkoski, T., Jiao, H., Kaminen‐Ahola, N., Tapia‐Páez, I., Ullah, M. S., Parton, L. E., Schuit, F. C., Quintens, R., Sipilä, I., Mayatepek, E., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/520960 · Cited by 235 · see citing works
Diagnosis and Localization of Focal Congenital Hyperinsulinism by 18F-Fluorodopa PET Scan
Hardy, O. T., Hernandez‐Pampaloni, M., Saffer, J. R., Suchi, M., Ruchelli, E. D., Zhuang, H., Ganguly, A. A., Freifelder, R. H., Adzick, N. S., Alavi, A. A., et al. (2007) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2006.08.028 · Cited by 231 · see citing works
Dunne, M. J., & Petersen, O. H. (1986) · FEBS Letters · doi:10.1016/0014-5793(86)81532-0 · Cited by 229 · see citing works
Kane, C., Shepherd, R. M., Squires, P. E., Johnson, P., James, R. F. L., Milla, P. J., Aynsley-Green, A., Lindley, K. J., & Dunne, M. J. (1996) · Nature Medicine · doi:10.1038/nm1296-1344 · Cited by 225 · see citing works
Dunne, M. J., Kane, C., Shepherd, R. M., Sánchez, J. A., James, R. F. L., Johnson, P., Aynsley-Green, A., Lu, S., Clement, J. P., Lindley, K. J., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199703063361005 · Cited by 219 · cited 1× · see citing works
“2 subunits of the pancreatic b -cell ATP-sensitive K C (K ATP ) channel respectively, are the most common known cause of CHI (9, 10, 11, 12).”
Pinney, S. E., MacMullen, C., Becker, S. A., Lin, Y., Hanna, C. E., THORNTON, P. S., Ganguly, A. A., Shyng, S., & Stanley, C. A. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35414 · Cited by 204 · see citing works
Molven, A., Matre, G. E., Durán, M., Wanders, R. J. A., Rishaug, U., Njølstad, P. R., Jellum, E., & Sövik, O. (2004) · Diabetes · doi:10.2337/diabetes.53.1.221 · Cited by 202 · cited 1× · see citing works
“Loss-of-function mutations in the HADH gene are associated with CHI and protein sensitivity but with normal serum ammonia levels (21, 22, 23, 24, 25).”
Severe Persistent Hyperinsulinemic Hypoglycemia due to a De Novo Glucokinase Mutation
Cuesta-Muñoz, A. L., Huopio, H., Otonkoski, T., Gómez‐Zumaquero, J. M., Näntö‐Salonen, K., Rahier, J., López-Enriquez, S., García-Gimeno, M. A., Sanz, P., Soriguer, F. C., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.8.2164 · Cited by 197 · cited 1× · see citing works
“Heterozygous activating GCK mutations cause CHI, which in most cases is medically responsive but in some cases surgery may be required (18, 19, 20).”
Li, C., Chen, P., Palladino, A., Narayan, S. B., Russell, L. K., Sayed, S. U., Xiong, G., Chen, J., Stokes, D., Butt, Y. M., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.123638 · Cited by 179 · see citing works
Novel Presentations of Congenital Hyperinsulinism due to Mutations in the MODY genes:HNF1AandHNF4A
Stanescu, D. E., Hughes, N., Kaplan, B., Stanley, C. A., & León, D. D. D. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1356 · Cited by 173 · see citing works
Shyng, S., Ferrigni, T., Shepard, J. B., Nestorowicz, A., Gläser, B., Permutt, M. A., & Nichols, C. G. (1998) · Diabetes · doi:10.2337/diabetes.47.7.1145 · Cited by 165 · see citing works
Cartier, E. A., Conti, L. R., Vandenberg, C. A., & Shyng, S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051499698 · Cited by 164 · see citing works
Otonkoski, T., Ämmälä, C., Huopio, H., Cote, G. J., Chapman, J., Cosgrove, K. E., Ashfield, R., Huang, E. S., Komulainen, J., Ashcroft, F. M., et al. (1999) · Diabetes · doi:10.2337/diabetes.48.2.408 · Cited by 155 · cited 1× · see citing works
“Two ABCC8 mutations, c.3992-9G O A and p.F1388del, are associated with CHI in the Ashkenazi Jewish population (11) and the p.V187D mutation has been associated with the Finnish population (46).”
Heterogeneity of persistent hyperinsulinaemic hypoglycaemia. A series of 175 cases
de Lonlay, P., Fournet, J., Touati, G., Groos, M.-S., Martin, D., Sevin, C., Delagne, V., Mayaud, C., Chigot, V., Sempoux, C. L., et al. (2001) · European Journal of Pediatrics · doi:10.1007/s004310100847 · Cited by 151 · see citing works
Kapoor, R. R., Locke, J. M., Colclough, K., Wales, J. K., CONN, J. J., Hattersley, A. T., Ellard, S., & Hussain, K. (2008) · Diabetes · doi:10.2337/db07-1657 · Cited by 151 · see citing works
Self-citationOtonkoski, T., Kaminen‐Ahola, N., Ustinov, J., Lapatto, R., Meißner, T., Mayatepek, E., Kere, J., & Sipilä, I. (2003) · Diabetes · doi:10.2337/diabetes.52.1.199 · Cited by 150 · cited 1× · see citing works
“Mutations in the promoter region of SLC16A1 gene have been described in patients with exercise-induced HI (26, 27).”
Rahier, J., Guiot, Y., & Sempoux, C. L. (2000) · Archives of Disease in Childhood Fetal & Neonatal · doi:10.1136/fn.82.2.f108 · Cited by 149 · see citing works
The genetic basis of congenital hyperinsulinism
James, C. T., Kapoor, R. R., Ismail, D., & Hussain, K. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.064337 · Cited by 148 · cited 1× · see citing works
“So far, mutations in eight different genes ( ABCC8 , KCNJ11 , GLUD1 , GCK , HADH , SLC16A1 , HNF4A and HNF1A ) that lead to dysregulated secretion of insulin have been described (7, 8).”
Self-citationDiazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations
Flanagan, S. E., Kapoor, R. R., Mali, G., Cody, D., Murphy, N., Schwahn, B., Siahanidou, T., Banerjee, I., Akçay, T., Rubio‐Cabezas, O., et al. (2010) · European Journal of Endocrinology · doi:10.1530/eje-09-0861 · Cited by 143 · cited 1× · see citing works
“The phenotypic characteristics of these patients have been previously reported (37).”
Self-citationHsu, B. Y. L., Kelly, A. T., THORNTON, P. S., Greenberg, C. R., Dilling, L. A., & Stanley, C. A. (2001) · The Journal of Pediatrics · doi:10.1067/mpd.2001.111818 · Cited by 141 · cited 1× · see citing works
“However, some forms of CHI demonstrate protein and/or leucine sensitivity and symptoms are manifested or aggravated in the postprandial period following a protein-rich meal rather than a fast (5).”
InfluentialHyperinsulinaemic hypoglycaemia
Kapoor, R. R., Flanagan, S. E., James, C. T., Hamilton-Shield, J. P., Ellard, S., & Hussain, K. (2009) · Archives of Disease in Childhood · doi:10.1136/adc.2008.148171 · Cited by 141 · cited 1× · see citing works
“Patients with a secondary cause of hyperinsulinaemic hypogly-caemia such as perinatal asphyxia, intra-uterine growth restriction, Rhesus isoimmunisation and syndromic forms such as Beckwith–Wiedemann syndrome were excluded from the study (33).”
Self-citationGenetic Heterogeneity in Familial Hyperinsulinism
Nestorowicz, A., Gläser, B., Wilson, B. A., Shyng, S., Nichols, C. G., Stanley, C. A., THORNTON, P. S., & Permutt, M. A. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.7.1119 · Cited by 122 · see citing works
Stanley, C. A. (2004) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2003.10.013 · Cited by 119 · cited 1× · see citing works
“Gain-of-function mutations in the GLUD1 gene, which encodes for the intra-mitochondrial enzyme glutamate dehydrogenase (GDH), form the molecular and biochemical basis of the hyperinsulinism and hyperammonaemia (HI/HA) syndrome and explain the link between leucine hypersensitivity and the HA (17).”
Bellanné‐Chantelot, C., Saint‐Martin, C., Ribeiro, M.-J., Vaury, C., Verkarre, V., Arnoux, J.-B., Valayannopoulos, V., Gobrecht, S., Sempoux, C. L., Rahier, J., et al. (2010) · Journal of Medical Genetics · doi:10.1136/jmg.2009.075416 · Cited by 118 · cited 1× · see citing works
“The mechanism of diffuse disease in patients with a heterozygous paternal ABCC8/KCNJ11 mutation is not understood, but similar observations have been documented in a previous study (45).”
Sayed, S. U., Langdon, D. R., Odili, S., Chen, P., Buettger, C. W., Schiffman, A. B., Suchi, M., Taub, R. A., Grimsby, J. S., Matschinsky, F. M., et al. (2009) · Diabetes · doi:10.2337/db08-1792 · Cited by 116 · see citing works
Yan, F.-F., Lin, Y., MacMullen, C., Ganguly, A. A., Stanley, C. A., & Shyng, S. (2007) · Diabetes · doi:10.2337/db07-0150 · Cited by 110 · see citing works
Gloyn, A. L., Siddiqui, J., & Ellard, S. (2006) · Human Mutation · doi:10.1002/humu.20292 · Cited by 108 · see citing works
Self-citationStanley, C. A., THORNTON, P. S., Ganguly, A. A., MacMullen, C., UNDERWOOD, P. C., Bhatia, P., Steinkrauss, L. J., Wanner, L. A., Kaye, R. D., Ruchelli, E. D., et al. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030965 · Cited by 104 · see citing works
p57KIP2 Expression in Normal Islet Cells and in Hyperinsulinism of Infancy
Kassem, S., Ariel, I., THORNTON, P. S., Hussain, K., Smith, V. V., Lindley, K. J., Aynsley-Green, A., & Gläser, B. (2001) · Diabetes · doi:10.2337/diabetes.50.12.2763 · Cited by 102 · see citing works
Self-citationKapoor, R. R., Flanagan, S. E., Fulton, P., Chakrapani, A., Chadefaux, B., Ben‐Omran, T., Banerjee, I., Hamilton-Shield, J. P., Ellard, S., & Hussain, K. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0615 · Cited by 99 · cited 1× · see citing works
“The genotype– phenotype correlations of these patients have been reported (36).”
Self-citationHyperinsulinaemic hypoglycaemia and diabetes mellitus due to dominant ABCC8/KCNJ11 mutations
Kapoor, R. R., Flanagan, S. E., James, C. T., McKiernan, J., Thomas, A., Harmer, S. C., Hamilton-Shield, J. P., Tinker, A., Ellard, S., & Hussain, K. (2011) · Diabetologia · doi:10.1007/s00125-011-2207-4 · Cited by 98 · cited 3× · see citing works
“…acting as i) the family member testing demonstrated that the mutation had arisen de novo , ii) a second mutation was not detected by sequencing or MLPA analysis and iii) a different mutation affecting the same residue has been reported previously in patients with dominantly inherited CHI (13, 34).”
Self-citationChristesen, H. T., Tribble, N. D., Molven, A., Siddiqui, J., Sandal, T., Brusgaard, K., Ellard, S., Njølstad, P. R., Alm, J., Jacobsen, B. B., et al. (2008) · European Journal of Endocrinology · doi:10.1530/eje-08-0203 · Cited by 88 · see citing works
Self-citationThe surgical management of congenital hyperinsulinemic hypoglycemia in infancy
Nihoul‐Feketé, C., de Lonlay, P., Jaubert, F., Rahier, J., Brunelle, F., & Saudubray, J. (2004) · Journal of Pediatric Surgery · doi:10.1016/j.jpedsurg.2003.11.004 · Cited by 86 · see citing works
Banerjee, I., Skae, M. S., Flanagan, S. E., Rigby, L., Patel, L., Didi, M., Blair, J., Ehtisham, S., Ellard, S., Cosgrove, K. E., et al. (2011) · European Journal of Endocrinology · doi:10.1530/eje-10-1136 · Cited by 86 · see citing works
Self-citationTornovsky-Babeay, S., Crane, A., Cosgrove, K. E., Hussain, K., Lavie, J., Heyman, M., Nesher, Y., Kuchinski, N., Ben-Shushan, E., Shatz, O., et al. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1233 · Cited by 86 · see citing works
Self-citationGläser, B., Ryan, F., Donath, M. Y., Landau, H., Stanley, C. A., Baker, L. W., Barton, D. E., & THORNTON, P. S. (1999) · Diabetes · doi:10.2337/diabetes.48.8.1652 · Cited by 81 · see citing works
Kapoor, R. R., James, C. T., Flanagan, S. E., Ellard, S., Eaton, S. D., & Hussain, K. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0423 · Cited by 80 · see citing works
Self-citationPermanent diabetes during the first year of life: multiple gene screening in 54 patients
the ISPED Early Diabetes Study Group, Russo, L., Iafusco, D., Brescianini, S., Nocerino, V., Bizzarri, C., Toni, S., Cerutti, F., Monciotti, C., Pesavento, R., et al. (2011) · Diabetologia · doi:10.1007/s00125-011-2094-8 · Cited by 73 · see citing works
Histopathology of Congenital Hyperinsulinism: Retrospective Study with Genotype Correlations
Suchi, M., MacMullen, C., THORNTON, P. S., Ganguly, A. A., Stanley, C. A., & Ruchelli, E. D. (2003) · Pediatric and Developmental Pathology · doi:10.1007/s10024-002-0026-9 · Cited by 72 · see citing works
Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism
Suchi, M., MacMullen, C., THORNTON, P. S., Adzick, N. S., Ganguly, A. A., Ruchelli, E. D., & Stanley, C. A. (2005) · Modern Pathology · doi:10.1038/modpathol.3800497 · Cited by 71 · see citing works
Hyperinsulinism of infancy associated with a novel splice site mutation in the SCHAD gene
Hussain, K., Clayton, P. T., Krywawych, S., Chatziandreou, I., Mills, P. B., Ginbey, D. W., Geboers, A. J. J. M., Berger, R., van den Berg, I. E. T., & Eaton, S. D. (2005) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2005.01.032 · Cited by 70 · cited 1× · see citing works
“Loss-of-function mutations in the HADH gene are associated with CHI and protein sensitivity but with normal serum ammonia levels (21, 22, 23, 24, 25).”
Self-citationMacMullen, C., Zhou, Q., Snider, K. E., Tewson, P. H., Becker, S. A., Aziz, A. R., Ganguly, A. A., Shyng, S., & Stanley, C. A. (2011) · Diabetes · doi:10.2337/db10-1631 · Cited by 70 · see citing works
Tanizawa, Y., Matsuda, K., Matsuo, M., Ohta, Y., Ochi, N., Adachi, M., Koga, M., Mizuno, S., Kajita, M., Tanaka, Y., et al. (2000) · Diabetes · doi:10.2337/diabetes.49.1.114 · Cited by 66 · see citing works
Transmembrane Topology of the Sulfonylurea Receptor SUR1
Conti, L. R., Radeke, C. M., Shyng, S., & Vandenberg, C. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106555200 · Cited by 64 · see citing works
Mutation spectra ofABCC8 gene in Spanish patients with hyperinsulinism of infancy (HI)
Marmiesse, A. F., Salas, A., Vega, A., Lorenzo, J. R. F., Barreiro, J., & Carracedo, Á. (2006) · Human Mutation · doi:10.1002/humu.9401 · Cited by 56 · see citing works
Factors Determining Patient Choice of Device for GH Therapy
Wickramasuriya, B. P. N., Casey, A., Akhtar, S., Zia, R., Ehtisham, S., Barrett, T. G., Shaw, N. J., & Kirk, J. M. W. (2005) · Hormone Research in Paediatrics · doi:10.1159/000090375 · Cited by 55 · see citing works
Comparative aspects of the function and mechanism of SUR1 and MDR1 proteins.
Ueda, K., Matsuo, M., Tanabe, K., Morita, K., Kioka, N., & Amachi, T. (1999) · Biochimica et Biophysica Acta · doi:10.1016/s0005-2736(99)00157-1 · Cited by 54 · cited 1× · see citing works
“These binding domains cooperate with each other in mediating the nucleotide regulation of the pore function (39).”
Flanagan, S. E., Kapoor, R. R., Banerjee, I., Hall, C., Smith, V. V., Hussain, K., & Ellard, S. (2010) · Clinical Genetics · doi:10.1111/j.1399-0004.2010.01476.x · Cited by 46 · see citing works
Self-citationMatsuo, M., Trapp, S., Tanizawa, Y., Kioka, N., Amachi, T., Oka, Y., Ashcroft, F. M., & Ueda, K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m006503200 · Cited by 43 · cited 1× · see citing works
“…inactivating ABCC8 and KCNJ11 mutations involves multiple defects in channel biogenesis and turnover, in channel trafficking from the endoplasmic reticulum and Golgi apparatus to the plasma membrane and alterations in the sensitivity of the channel to both magnesium ATP and ADP (14, 15, 16).”
Yorifuji, T., Kawakita, R., Nagai, S., Sugimine, A., Doi, H., Nomura, A., Masue, M., Nishibori, H., Yoshizawa, A., Okamoto, S., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1281 · Cited by 43 · see citing works
Adjacent mutations in the gating loop of Kir6.2 produce neonatal diabetes and hyperinsulinism
Shimomura, K., Flanagan, S., Zadek, B., Lethby, M., Zubcevic, L., Girard, C., Petz, O., Männikkö, R., Kapoor, R., Hussain, K., et al. (2009) · EMBO Molecular Medicine · doi:10.1002/emmm.200900018 · Cited by 41 · cited 1× · see citing works
“In one of these patients (patient 148), who has been reported previously, a giant focal lesion was observed (35).”
Self-citationDarendelıler, F., Fournet, J., Baş, F., Junien, C., Gross, M., Bundak, R., Saka, N., & Günöz, H. (2002) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2002.15.7.993 · Cited by 38 · see citing works
Familial Focal Congenital Hyperinsulinism
Ismail, D., Smith, V. V., de Lonlay, P., Ribeiro, M. J., Rahier, J., Blankenstein, O., Flanagan, S. E., Bellanné‐Chantelot, C., Verkarre, V., Aigrain, Y. Y., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1524 · Cited by 37 · see citing works
Self-citationPark, S. E., Flanagan, S. E., Hussain, K., Ellard, S., Shin, C. H., & Yang, S. W. (2011) · European Journal of Endocrinology · doi:10.1530/eje-11-0160 · Cited by 37 · see citing works
Self-citationGiurgea, I., Sempoux, C. L., Bellanné‐Chantelot, C., Ribeiro, M. J., Hubert, L., Boddaert, N., Saudubray, J., Robert, J., Brunelle, F., Rahier, J., et al. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0397 · Cited by 36 · see citing works
The Heterogeneity of Focal Forms of Congenital Hyperinsulinism
Ismail, D., Kapoor, R. R., Smith, V. V., Ashworth, M. T., Blankenstein, O., Pierro, A., Flanagan, S. E., Ellard, S., & Hussain, K. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1628 · Cited by 33 · see citing works
Self-citationThe spectrum of ABCC8 mutations in Norwegian patients with congenital hyperinsulinism of infancy
Sandal, T., Laborie, L., Brusgaard, K., Eide, S., Christesen, H. T., Søvik, O., Pr, N., & Molven, A. (2009) · Clinical Genetics · doi:10.1111/j.1399-0004.2009.01152.x · Cited by 32 · see citing works
Kumaran, A., Kapoor, R. R., Flanagan, S. E., Ellard, S., & Hussain, K. (2010) · Hormone Research in Paediatrics · doi:10.1159/000284394 · Cited by 26 · see citing works
Self-citationComplex ABCC8 DNA variations in congenital hyperinsulinism: lessons from functional studies
Muzyamba, M. C., Farzaneh, T., Behe, P., Thomas, A., Christesen, H. T., Brusgaard, K., Hussain, K., & Tinker, A. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.02847.x · Cited by 25 · see citing works
Self-citationÖçal, G., Flanagan, S. E., Hacıhamdioğlu, B., Berberoğlu, M., Şıklar, Z., Ellard, S., Erdeve, Ş. S., Okulu, E., Akın, İ. M., Atasay, B., et al. (2011) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2011.347 · Cited by 24 · see citing works
Self-citationGenotype-Phenotype Associations in Patients with Severe Hyperinsulinism of Infancy
Greer, R. M., Shah, J. H., Jeske, Y. W. A., Brown, D., Walker, R. M., Cowley, D. M., Bowling, F. G., Liaskou, D., Harris, M. A., Thomsett, M. J., et al. (2007) · Pediatric and Developmental Pathology · doi:10.2350/06-04-0083.1 · Cited by 20 · see citing works
Powell, P. D., Bellanné‐Chantelot, C., Flanagan, S. E., Ellard, S., Rooman, R., Hussain, K., Skae, M. S., Clayton, P., de Lonlay, P., Dunne, M. J., et al. (2011) · Diabetes · doi:10.2337/db10-1443 · Cited by 19 · see citing works
Self-citationKapoor, R. R., Flanagan, S. E., Ellard, S., & Hussain, K. (2011) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2011.04203.x · Cited by 12 · see citing works
Self-citationPrenatal Diagnosis and Postnatal Management of Diffuse Congenital Hyperinsulinism: A Case Report
Peranteau, W. H., Ganguly, A. A., Steinmuller, L., THORNTON, P. S., Johnson, M. P., Howell, L. J., Stanley, C. A., & Adzick, N. S. (2006) · Fetal Diagnosis and Therapy · doi:10.1159/000095664 · Cited by 12 · see citing works
Permanent Neonatal Diabetes Caused by a Novel Mutation
Jain, V., Kumar, S., Flanagan, S. E., & Ellard, S. (2012) · Indian Pediatrics · doi:10.1007/s13312-012-0093-6 · Cited by 11 · see citing works
Self-citationCongenital hyperinsulinism caused by mutations in ABCC8 (SUR1) gene.
Thakur, S., Flanagan, S. E., Ellard, S., & Verma, I. C. (2011) · PubMed · Cited by 6 · see citing works
Self-citationHosy, E., Dupuis, J. P., & Vivaudou, M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.043307 · Cited by 5 · see citing works
(2012) · Pediatric Diabetes · doi:10.1111/j.1399-5448.2012.00887.x · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Eds C Stanley & DD de Leon. In Monogenic Hyperinsulinemic Hypoglycemia Disorders (Frontiers in Diabetes). Philadelphia: Karger, 2012.
Cited by
Sorted by citations
Genetic Analysis of Italian Patients with Congenital Hyperinsulinism of Infancy
Valin, P. S., Proverbio, M. C., Diceglie, C., Gessi, A., Candia, S. D., Mariani, B., Zamproni, I., Mangano, E., Asselta, R., Battaglia, C., et al. (2013) · Hormone Research in Paediatrics · doi:10.1159/000350827 · Cited by 552 · see citing works
Franco, E. D., Saint‐Martin, C., Brusgaard, K., Johnson, A. E. K., Aguilar‐Bryan, L., Bowman, P., Arnoux, J., Larsen, A. R., Sanyoura, M., Greeley, S. A. W., et al. (2020) · Human Mutation · doi:10.1002/humu.23995 · Cited by 179 · see citing works
“Mutations in these two genes together account for 36–70% of CHI cases (Kapoor et al., 2013; Snider et al., 2013).”
BackgroundSelf-citationCongenital Hyperinsulinism: Diagnosis and Treatment Update
Demirbilek, H., & Hussain, K. (2018) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.2017.s007 · Cited by 165 · see citing works
“HH can be transient due to certain risk factors, such as birth asphyxia, intra-uterine growth retardation, maternal diabetes mellitus (5), or associated with various overgrowth syndromes like Beckwith-Wiedemann syndrome or metabolic conditions such as congenital disorders of glycosylation (6).”
BackgroundInfluentialSelf-citationCongenital hyperinsulinism: current status and future perspectives
Yorifuji, T. (2014) · Annals of Pediatric Endocrinology & Metabolism · doi:10.6065/apem.2014.19.2.57 · Cited by 156 · see citing works
Therapies and outcomes of congenital hyperinsulinism‐induced hypoglycaemia
Banerjee, I., Salomon‐Estebanez, M., Shah, P., Nicholson, J., Cosgrove, K. E., & Dunne, M. J. (2018) · Diabetic Medicine · doi:10.1111/dme.13823 · Cited by 142 · see citing works
International Guidelines for the Diagnosis and Management of Hyperinsulinism
León, D. D. D., Arnoux, J. B., Banerjee, I., Bergadá, I., Bhatti, T. R., Conwell, L. S., Fu, J., Flanagan, S. E., Gillis, D. J., Meißner, T., et al. (2023) · Hormone Research in Paediatrics · doi:10.1159/000531766 · Cited by 125 · see citing works
Self-citationThe Genetic and Molecular Mechanisms of Congenital Hyperinsulinism
Galcheva, S., Demirbilek, H., Al-Khawaga, S., & Hussain, K. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00111 · Cited by 99 · see citing works
“They are likely to have dominant acting CHI, exerting the effect of the heterozygous ABCC8/KCNJ11 mutations by a dominant-negative mechanism leading to diffuse CHI (27, 36, 60, 61).”
BackgroundSelf-citationWelters, A., Lerch, C., Kummer, S., Marquard, J., Salgin, B., Mayatepek, E., & Meißner, T. (2015) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-015-0367-x · Cited by 96 · see citing works
“However, in almost 50 % of CHI-cases, the genetic mechanism is still unknown, suggesting further disease-associated genes [2, 3].”
BackgroundCongenital hyperinsulinism disorders: Genetic and clinical characteristics
Rosenfeld, E., Ganguly, A. A., & León, D. D. D. (2019) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31737 · Cited by 95 · see citing works
“…advances which have expanded our understanding of the pathophysiology of this disorder, the cause of HI remains unknown in up to 50% of patients suggesting the role of additional genetic loci that have yet to be discovered (Kapoor et al., 2013; Martinez et al., 2016; Snider et al., 2013).”
BackgroundFlanagan, S. E., Vairo, F. P. E., Johnson, M. B., Caswell, R. C., Laver, T. W., Allen, H. L., Hussain, K., & Ellard, S. (2017) · Pediatric Diabetes · doi:10.1111/pedi.12512 · Cited by 90 · see citing works
“The absence of mutations may reflect the low proportion of individuals with cardiac disease in the cohort (6 of 60) or it may represent the low prevalence of CACNA1D mutations in individuals with HH.”
BackgroundInfluentialSelf-citationGüemes, M., Rahman, S. A., Kapoor, R. R., Flanagan, S. E., Houghton, J., Misra, S., Oliver, N. S., Dattani, M., & Shah, P. (2020) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-020-09548-7 · Cited by 88 · see citing works
Self-citationClinical practice guidelines for congenital hyperinsulinism
Yorifuji, T., Horikawa, R., Hasegawa, T., Adachi, M., Soneda, S., Minagawa, M., Ida, S., Yonekura, T., Kinoshita, Y., Kanamori, Y., et al. (2017) · Clinical Pediatric Endocrinology · doi:10.1297/cpe.26.127 · Cited by 74 · see citing works
“• Approximately 90% of patients with diazoxide unresponsive CHI have mutations in the KATP channel genes, ABCC8 or KCNJ11) (78, 79).”
BackgroundThe Diagnosis and Management of Hyperinsulinaemic Hypoglycaemia
Roženková, K., Güemes, M., Shah, P., & Hussain, K. (2015) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.1891 · Cited by 77 · see citing works
“On the other hand, patients carrying mutations in the remaining known CHI genes are usually diazoxideresponsive (5,15).”
BackgroundInfluentialSelf-citationUpdate on neonatal hypoglycemia
Rozance, P. J. (2013) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000027 · Cited by 74 · see citing works
“Dominant KATP mutations could be either diazoxide-responsive or unresponsive [40,41].”
BackgroundResultInfluentialMolecular mechanisms of congenital hyperinsulinism
Rahman, S. A., Nessa, A., & Hussain, K. (2015) · Journal of Molecular Endocrinology · doi:10.1530/jme-15-0016 · Cited by 69 · see citing works
“3% of all CHI cases (Kapoor et al. 2013).”
BackgroundInfluentialSelf-citationSalomon‐Estebanez, M., Flanagan, S. E., Ellard, S., Rigby, L., Bowden, L., Mohamed, Z., Nicholson, J., Skae, M. S., Hall, C., Craigie, R., et al. (2016) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-016-0547-3 · Cited by 69 · see citing works
“disease have been reported [10–12], mostly in those without known genetic mutations, while cohort studies in different countries have characterised surgical outcomes only [4, 7, 8, 13].”
BackgroundResultSelf-citationWakeling, M. N., Owens, N. D. L., Hopkinson, J. R., Johnson, M. B., Houghton, J., Dastamani, A., Flaxman, C. S., Wyatt, R. C., Hewat, T. I., Hopkins, J. J., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01204-x · Cited by 66 · see citing works
“It is a clinically and genetically heterogeneous disease where, despite extensive sequencing efforts, the underlying aetiology is not known in up to 50% of individuals 8,9 .”
Self-citationHyperinsulinemic Hypoglycemia – The Molecular Mechanisms
Nessa, A., Rahman, S. A., & Hussain, K. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00029 · Cited by 65 · see citing works
Self-citationLong-Term Follow-Up of Children With Congenital Hyperinsulinism on Octreotide Therapy
Demirbilek, H., Shah, P., Arya, V. B., Hinchey, L., Flanagan, S. E., Ellard, S., & Hussain, K. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1866 · Cited by 65 · see citing works
Self-citationBanerjee, I., Raskin, J., Arnoux, J., León, D. D. D., WEINZIMER, S. A., Hammer, M., Kendall, D. M., & THORNTON, P. S. (2022) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-022-02214-y · Cited by 62 · see citing works
Baier, L. J., Muller, Y. L., Remedi, M. S., Traurig, M. T., Piaggi, P., Wiessner, G. B., Huang, K., Stacy, A., Kobes, S., Krakoff, J. A., et al. (2015) · Diabetes · doi:10.2337/db15-0459 · Cited by 61 · see citing works
“not observed on a population level (14,15).”
Szymanowski, M., Salomon‐Estebanez, M., Padidela, R., Han, B., Mosinska, K., Stevens, A., Damaj, L., Bars, F. P., Lascouts, E., Reynaud, R., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2711 · Cited by 56 · see citing works
MN, W., L, J., JW, H., KS, R., J, T., AT, H., & CF, W. (2021) · BMJ · doi:10.1136/bmj.n214 · Cited by 51 · see citing works
Arya, V. B., Güemes, M., Nessa, A., Alam, S. T., Shah, P., Gilbert, C., Senniappan, S., Flanagan, S. E., Ellard, S., & Hussain, K. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0353 · Cited by 51 · see citing works
Self-citationvan der Steen, I., van Albada, M. E., Mohnike, K. L., Christesen, H. T., Empting, S., Salomon‐Estebanez, M., Rasmussen, A. G., Stuart, A. V., van der Linde, A. A. A., Banerjee, I., et al. (2017) · Hormone Research in Paediatrics · doi:10.1159/000485184 · Cited by 49 · see citing works
Hewat, T. I., Johnson, M. B., & Flanagan, S. E. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.873254 · Cited by 48 · see citing works
“Loss-of-function variants in the ABCC8 and KCNJ11 genes, which encode the two subunits of the pancreatic beta-cell ATP-sensitive potassium (KATP) channel, are most common and reported in 30-66% of cases referred for genetic testing (3, 4, 26, 27).”
BackgroundMethodSelf-citationA Clinical Review of Generalized Overgrowth Syndromes in the Era of Massively Parallel Sequencing
Kamien, B., Ronan, A., Poke, G., Sinnerbrink, I. B., Baynam, G. S., Ward, M., Gibson, W. T., Dudding‐Byth, T., & Scott, R. J. (2018) · Molecular Syndromology · doi:10.1159/000484532 · Cited by 48 · see citing works
“Familial hyperinsulinism ABCC8, KCNJ11, GCK, HADH, GLUD1, SLC16A1, HNF4A, HNF1A usually AR, sometimes AD Severe hypoglycemia at birth often associated with macrosomia [Kapoor et al., 2013; Glaser, 2017]”
BackgroundGenetic characteristics of patients with congenital hyperinsulinism
Vajravelu, M. E., & León, D. D. D. (2018) · Current Opinion in Pediatrics · doi:10.1097/mop.0000000000000645 · Cited by 47 · see citing works
Hyperinsulinaemic Hypoglycaemia
Arya, V., Mohammed, Z., Blankenstein, O., de Lonlay, P., & Hussain, K. (2014) · Hormone and Metabolic Research · doi:10.1055/s-0034-1367063 · Cited by 18 · see citing works
Self-citationDiagnosis and management of hyperinsulinaemic hypoglycaemia.
Galcheva, S., Al-Khawaga, S., & Hussain, K. (2018) · Best practice & research. Clinical endocrinology & metabolism · doi:10.1016/j.beem.2018.05.014 · Cited by 33 · see citing works
Self-citationHuman Pluripotent Stem Cells to Model Islet Defects in Diabetes
Balboa, D., Iworima, D. G., & Kieffer, T. J. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.642152 · Cited by 47 · see citing works
“glutamate into TCA, ATP generation, and insulin secretion CHI (55, 56)”
BackgroundInfluentialMohnike, K. L., Wieland, I., Barthlen, W., Vogelgesang, S., Empting, S., Mohnike, W., Meißner, T., & Zenker, M. (2014) · Hormone Research in Paediatrics · doi:10.1159/000356905 · Cited by 45 · see citing works
Roženková, K., Malíková, J., Nessa, A., Dušátková, L., Bjørkhaug, L., Obermannová, B., Dušátková, P., Kytnarová, J., Aukrust, I., Najmi, L. A., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2763 · Cited by 44 · see citing works
Self-citationInsulinoma in childhood: clinical, radiological, molecular and histological aspects of nine patients
Padidela, R., Fiest, M., Arya, V. B., Smith, V. V., Ashworth, M. T., Rampling, D., Newbould, M. J., Batra, G., James, J. M., Wright, N., et al. (2014) · European Journal of Endocrinology · doi:10.1530/eje-13-1008 · Cited by 44 · see citing works
Self-citationMaturity Onset Diabetes of the Young—New Approaches for Disease Modelling
Skoczek, D., Dulak, J., & Kachamakova‐Trojanowska, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147553 · Cited by 43 · see citing works
Han, B., Newbould, M. J., Batra, G., Cheesman, E., Craigie, R., Mohamed, Z., Rigby, L., Padidela, R., Skae, M. S., Mironov, A., et al. (2016) · American Journal of Clinical Pathology · doi:10.1093/ajcp/aqw075 · Cited by 41 · see citing works
Congenital hyperinsulinism: recent updates on molecular mechanisms, diagnosis and management
Giri, D., Hawton, K., & Senniappan, S. (2021) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2021-0369 · Cited by 41 · see citing works
Persistent hyperinsulinaemic hypoglycaemia in infancy
Shah, P., Demirbilek, H., & Hussain, K. (2014) · Seminars in Pediatric Surgery · doi:10.1053/j.sempedsurg.2014.03.005 · Cited by 40 · see citing works
Self-citationMolecular genetic testing of patients with monogenic diabetes and hyperinsulinism
Bennett, J. T., Vasta, V., Zhang, M., Narayanan, J., Gerrits, P., & Hahn, S. H. (2014) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2014.12.304 · Cited by 40 · see citing works
“identify mutations in 55–73% of probands referred for CHI or MODY testing [4,27].”
Risk Factors for Adverse Neurodevelopment in Transient or Persistent Congenital Hyperinsulinism
Roeper, M., Dafsari, R. S., Hoermann, H., Mayatepek, E., Kummer, S., & Meißner, T. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.580642 · Cited by 40 · see citing works
“However, the underlying genetic cause is only identified in about 50%–60% of patients (6, 7).”
BackgroundChristiansen, C. D., Petersen, H., Nielsen, A. L., Detlefsen, S., Brusgaard, K., Rasmussen, L. M., Melikyan, M. A., Ekström, K., Globa, E., Rasmussen, A. H., et al. (2017) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-017-3867-1 · Cited by 39 · see citing works
Next generation sequencing targeted gene panel in Greek MODY patients increases diagnostic accuracy
Tatsi, E., Kanaka‐Gantenbein, C., Scorilas, A., Chrousos, G. P., & Sertedaki, A. (2019) · Pediatric Diabetes · doi:10.1111/pedi.12931 · Cited by 38 · see citing works
“It has been proposed that ABCC8 related DM might be due to progressive β-cell function failure because of “exhaustion” or increased β-cell apoptosis as a result of increased intracellular calcium influx through the voltage-dependent calcium channel of the β-cell resulting in raised intracellular calcium concentration,…”
BackgroundSUR1-mutant iPS cell-derived islets recapitulate the pathophysiology of congenital hyperinsulinism
Lithovius, V., Saarimäki-Vire, J., Balboa, D., Ibrahim, H., Montaser, H., Barsby, T., & Otonkoski, T. (2021) · Diabetologia · doi:10.1007/s00125-020-05346-7 · Cited by 34 · see citing works
“Inactivating mutations in the beta cell KATP-channel genes are the most common cause of CHI (KATPHI), comprising 36–61% of all cases [2, 3].”
BackgroundHyperinsulinemic hypoglycemia in infancy: Current concepts in diagnosis and management
Vora, S., Chandran, S., Rajadurai, V. S., & Hussain, K. (2015) · Indian Pediatrics · doi:10.1007/s13312-015-0772-1 · Cited by 34 · see citing works
“Presentation of persistent hyperinsulinemic hypoglycemia is more severe needing higher concentrations of glucose to maintain the blood glucose level [34].”
BackgroundSelf-citationThe Shifting Landscape of KAtpChannelopathies and the Need for ‘Sharper’ Therapeutics
Kharade, S. V., Nichols, C. G., & Denton, J. S. (2016) · Future Medicinal Chemistry · doi:10.4155/fmc-2016-0005 · Cited by 34 · see citing works
Männistö, J. M. E., Jääskeläinen, J., Otonkoski, T., & Huopio, H. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab024 · Cited by 32 · see citing works
“Typically, diazoxide-responsive dominant CHI was more common in this study (27% of P-CHI patients) compared with other cohorts (20% to 21%) (6, 32) due to the Finnish founder mutation ABCC8/p.”
ResultInfluentialDemirbilek, H., Rahman, S. A., Büyükyılmaz, G., & Hussain, K. (2017) · International Journal of Pediatric Endocrinology · doi:10.1186/s13633-017-0048-8 · Cited by 31 · see citing works
“HH can be congenital (known as congenital hyperinsulinaemic hypoglycaemia) or secondary to certain risk factors like birth asphyxia, intra-uterine growth retardation [4], maternal diabetes mellitus or associated with various developmental syndromes such as Beckwith-Wiedemann syndrome or metabolic conditions like conge…”
BackgroundInfluentialSelf-citationMolecular mechanisms of congenital hyperinsulinism due to autosomal dominant mutations inABCC8
Nessa, A., Aziz, Q. H., Thomas, A., Harmer, S. C., Tinker, A., & Hussain, K. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv233 · Cited by 30 · see citing works
“A single patient has a novel SUR1 mutation (I1425L), whilst the others have previously reported dominantly inactivating heterozygous missense mutations in ABCC8 (16,21).”
BackgroundMethodInfluentialSelf-citationShah, P., Rahman, S. A., McElroy, S., Gilbert, C., Morgan, K., Hinchey, L., Senniappan, S., Levy, H., Amin, R., & Hussain, K. (2015) · Hormone Research in Paediatrics · doi:10.1159/000439131 · Cited by 29 · see citing works
Self-citationMathioudakis, L., Bourbouli, M., Daklada, E., Kargatzi, S., Michaelidou, K., & Zaganas, I. V. (2018) · Neurochemical Research · doi:10.1007/s11064-018-2575-y · Cited by 28 · see citing works
Demirbilek, H., Arya, V. B., Özbek, M. N., Akıncı, A., Doğan, M., Demirel, F., Houghton, J., Kaba, S., Güzel, F. B., Baran, R. T., et al. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0045 · Cited by 28 · see citing works
Self-citationComplexities in the medical management of hypoglycaemia due to congenital hyperinsulinism
Worth, C., Yau, D., Salomon‐Estebanez, M., O’Shea, E., Cosgrove, K. E., Dunne, M. J., & Banerjee, I. (2020) · Clinical Endocrinology · doi:10.1111/cen.14152 · Cited by 27 · see citing works
Nichols, C. G., York, N., & Remedi, M. S. (2022) · Diabetes · doi:10.2337/db21-0755 · Cited by 31 · see citing works
Personalized Therapeutics for KATP-Dependent Pathologies
Nichols, C. G. (2022) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-051921-123023 · Cited by 30 · see citing works
Hermann, F., Kjaergaard, M., Tian, C.-L., Tiemann, U., Jackson, A., Olsen, L. R., Kraft, M., Carlsson, P., Elfving, I. M., Kettunen, J., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.12.001 · Cited by 27 · see citing works
Shaikh, M. G., Lucas-Herald, A. K., Dastamani, A., Salomon‐Estebanez, M., Senniappan, S., Abid, N., Ahmad, S. R., Alexander, S., Avatapalle, B., Awan, N., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1231043 · Cited by 27 · see citing works
“The majority of pathogenic variants (69, 70) affect the ATP-sensitive K + (KATP) channels in the pancreatic beta-cells, whilst others affect the intracellular proteins and enzymes involved in regulation of the insulin secretion pathway.”
BackgroundSelf-citationGong, C., Huang, S., Su, C., Qi, Z., Liu, F., Wu, D., Cao, B., Gu, Y., Li, W., Liang, X., et al. (2015) · Pediatric Diabetes · doi:10.1111/pedi.12254 · Cited by 27 · see citing works
“6% of the 105 diazoxide-unresponsive patients (8).”
ResultClinical and genetic characterization of congenital hyperinsulinism in Spain
Martı́nez, R., Fernández-Ramos, C., Vela, A., Velayos, T., Aguayo, A., Urrutia, I., Rica, I., Castaño, L. A., & _, _. (2016) · European Journal of Endocrinology · doi:10.1530/eje-16-0027 · Cited by 27 · see citing works
Männistö, J. M. E., Maria, M., Raivo, J., Kuulasmaa, T., Otonkoski, T., Huopio, H., & Laakso, M. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz271 · Cited by 26 · see citing works
Işık, E., Demirbilek, H., Houghton, J., Ellard, S., Flanagan, S. E., & Hussain, K. (2019) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.galenos.2018.2018.0077 · Cited by 25 · see citing works
“Recessive inactivating mutations of the KATP channel genes (ABCC8 and KCNJ11) are the most common cause of severe, diazoxide unresponsive, diffuse CHI which usually requires pancreatectomy (1,10).”
BackgroundSelf-citationMaiorana, A., Barbetti, F., Boiani, A., Rufini, V., Pizzoferro, M., Francalanci, P., Faletra, F., Nichols, C. G., Grimaldi, C., de Goyet, J. D. V., et al. (2014) · Clinical Endocrinology · doi:10.1111/cen.12400 · Cited by 24 · see citing works
Weedon, M. N., Jackson, L., Harrison, J. W., Ruth, K. S., Tyrrell, J., Hattersley, A. T., & Wright, C. F. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/696799 · Cited by 19 · see citing works
Stimulus-Secretion Coupling in Beta-Cells: From Basic to Bedside
Islam, M. S. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-12457-1_37 · Cited by 23 · see citing works
Arya, V. B., Aziz, Q. H., Nessa, A., Tinker, A., & Hussain, K. (2014) · International Journal of Pediatric Endocrinology · doi:10.1186/1687-9856-2014-24 · Cited by 23 · see citing works
“Although dominant acting ABCC8/KCNJ11 mutations have been reported, recessively inherited mutations are more common [4,5,9,10].”
BackgroundSelf-citationGuo, D., Liu, H.-K., Ruzi, A., Gao, G., Nasir, A., Liu, Y., Yang, F., Wu, F., Xu, G., & Li, Y.-X. (2017) · Scientific Reports · doi:10.1038/s41598-017-03349-w · Cited by 21 · see citing works
Hyperinsulinemic hypoglycemia: clinical, molecular and therapeutical novelties
Maiorana, A., & Dionisi‐Vici, C. (2017) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-017-0059-x · Cited by 23 · see citing works
“…al 2011; Arya et al 2014a; Garg et al 2015 AKT3 Nellist et al 2015 PI3KCA De Leon and Stanley 2017 TRMT10A Gillis et al 2014 CACNA1D Flanagan et al 2017 Undiagnosed dysmorphisms Meissner et al 2001 (Touati et al 1998; Loechner et al 2011; Ismail et al 2012; Kapoor et al 2013; Maiorana et al 2014).”
BackgroundSaint‐Martin, C., Zhou, Q., Martin, G. M., Vaury, C., Leroy, G., Arnoux, J., de Lonlay, P., Shyng, S., & Bellanné‐Chantelot, C. (2014) · Clinical Genetics · doi:10.1111/cge.12428 · Cited by 23 · see citing works
Salisbury, R. J., Han, B., Jennings, R. E., Berry, A. A., Stevens, A., Mohamed, Z., Sugden, S. A., de Krijger, R. R., Cross, S. E., Johnson, P. P. V., et al. (2015) · Diabetes · doi:10.2337/db14-1202 · Cited by 23 · see citing works
“Inactivating mutations in either the ABCC8 or KCNJ11 genes, which encode subunits of the KATP channel, account for approximately 90% of those cases (3,4) where hypoglycemia necessitates partial or near-total pancreatectomy (1,2).”
BackgroundGenetic testing strategies in the newborn
Carroll, J. M., Wigby, K. M., & Murray, S. (2020) · Journal of Perinatology · doi:10.1038/s41372-020-0697-y · Cited by 21 · see citing works
Babiker, O., Flanagan, S. E., Ellard, S., Girim, H. A., Hussain, K., & Senniappan, S. (2015) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2015-0033 · Cited by 20 · see citing works
Self-citationÜnal, S., Gönülal, D., Uçaktürk, S. A., Bilgin, B. S., Flanagan, S. E., Gürbüz, F., Tayfun, M., Elmaoğulları, S., Yılmaz, A. A., Demirel, F., et al. (2016) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.2773 · Cited by 19 · see citing works
“5) result in focal pancreatic lesions (6,9,10,12,16).”
BackgroundSelf-citationMartı́nez, R., Gutierrez‐Nogués, Á., Fernández-Ramos, C., Velayos, T., Vela, A., Spanish Congenital Hyperinsulinism Group, Navas, M., & Castaño, L. A. (2017) · Clinical Endocrinology · doi:10.1111/cen.13318 · Cited by 19 · see citing works
Role of Actionable Genes in Pursuing a True Approach of Precision Medicine in Monogenic Diabetes
Marucci, A., Rutigliano, I., Fini, G., Pezzilli, S., Menzaghi, C., Paola, R. D., & Trischitta, V. (2022) · Genes · doi:10.3390/genes13010117 · Cited by 21 · see citing works
“approximately 100 in KCNJ11) [49–52], are predominantly recessive inherited [53] and account for 36–70% cases of congenital hyperinsulinemic hypoglycemia (HH) [54,55], which is not the focus of this article and which has been discussed in details elsewhere [56,57].”
BackgroundNi, J., Ge, J., Zhang, M., Hussain, K., Guan, Y., Cheng, R., Xi, L., Zheng, Z., Ren, S., & Luo, F. (2019) · European Journal of Pediatrics · doi:10.1007/s00431-019-03408-6 · Cited by 18 · see citing works
Self-citationManaging congenital hyperinsulinism: improving outcomes with a multidisciplinary approach
Palladino, A., & Ackermann, A. M. (2015) · Research and Reports in Endocrine Disorders · doi:10.2147/rred.s56608 · Cited by 18 · see citing works
“Focal Hi As mentioned in previous sections, the most common gene mutations to cause CHI are in ABCC8 and KCNJ11, with most of these cases being diazoxide unresponsive.(23,24) A paternally inherited heterozygous recessive mutation in either of these genes is highly associated with focal HI.”
Comparative meta‐analysis of Kabuki syndrome with and without hyperinsulinaemic hypoglycaemia
Hoermann, H., El‐Rifai, O., Schebek, M., Lodefalk, M., Brusgaard, K., Bachmann, N., Bergmann, C., Roeper, M., Welters, A., Dafsari, R. S., et al. (2020) · Clinical Endocrinology · doi:10.1111/cen.14267 · Cited by 18 · see citing works
Congenital Hyperinsulinism in China: A Review of Chinese Literature Over the Past 15 Years
Wang, W.-Y., Sun, Y., Zhao, W., Wu, T., Wang, L., Yuan, T., & Yu, H. (2017) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.3934 · Cited by 17 · see citing works
“Two HNF4A gene mutation cases were diazoxide-responsive in our study; Kapoor et al (37) also elucidated that CHI patients with HNF4A can exhibit mild, transient to severe, persistent hypoglycemia and are diazoxide-responsive.”
ResultInfluentialInsulinoma in childhood: a retrospective review of 22 patients from one referral centre
Melikyan, M. A., Gubaeva, D. N., Shadrina, A., Викторовна, Б. А., Kareva, M., Tiulpakov, A. N., Efremenkov, A. M., Sokolov, Y., Brusgaard, K., Christesen, H. T., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1127173 · Cited by 16 · see citing works
“While congenital hyperinsulinism is the most common cause for persistent and recurrent hypoglycemia in infancy (29), the possibility of insulinoma should be considered in those with HH presenting after the age of three years.”
BackgroundJahnavi, S., Varadarajan, P., Kanthimathi, S., Kandasamy, B., Bodhini, D., Yadav, J., Jain, V., Khadgawat, R., Sikdar, M., Bhavatharini, A., et al. (2014) · Annals of Human Genetics · doi:10.1111/ahg.12070 · Cited by 16 · see citing works
“Of note, a founder effect of the Gly111Arg mutation was reported recently in patients of Indian ethnic origin (Kapoor et al., 2013).”
BackgroundResultInfluentialPersistent hyperinsulinaemic hypoglycaemia in children with Rubinstein–Taybi syndrome
Welters, A., El‐Khairi, R., Dastamani, A., Bachmann, N., Bergmann, C., Gilbert, C., Clement, E. M., Hurst, J. A., Quercia, N. L., Wasserman, J. D., et al. (2019) · European Journal of Endocrinology · doi:10.1530/eje-19-0119 · Cited by 16 · see citing works
Çamtosun, E., Flanagan, S. E., Ellard, S., Şıklar, Z., Hussain, K., Kocaay, P., & Berberoğlu, M. (2015) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.1963 · Cited by 16 · see citing works
“So far, approximately 40 patients with CHH resulting from a mutation in the HADH gene have been reported (Table 1) (3,4,5,6,7,8,9,10,11,12, 13,14,15).”
Self-citationA syndrome of congenital hyperinsulinism and rhabdomyolysis is caused by KCNJ11 mutation
Albaqumi, M. N., Alhabib, F. A., Shamseldin, H. E., Mohammed, F., & Alkuraya, F. S. (2014) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2013-102085 · Cited by 15 · see citing works
Martino, M., Sartorelli, J., Gragnaniello, V., & Burlina, A. (2022) · Frontiers in Pediatrics · doi:10.3389/fped.2022.901338 · Cited by 15 · see citing works
“Symptoms of hypoglycemia can range from non-specific adrenergic symptoms (poor feeding, hunger, palpitations, sweating) to life-threatening, neuroglycopenic symptoms (seizures, unconsciousness, lethargy, coma and even death) (7).”
BackgroundCongenital hyperinsulinism: Global and Japanese perspectives
Yorifuji, T., Masue, M., & Nishibori, H. (2014) · Pediatrics International · doi:10.1111/ped.12390 · Cited by 15 · see citing works
Hyperinsulinemic Hypoglycaemia in a Turner Syndrome with Ring (X)
Cappella, M., Graziani, V., Pragliola, A., Sensi, A., Hussain, K., Muratori, C., & Marchetti, F. (2015) · Case Reports in Pediatrics · doi:10.1155/2015/561974 · Cited by 15 · see citing works
“The serum ammonia was normal sowe ruled out the hyperinsulinism-hyperammonaemia syndrome, the second common form of CHI (caused by mutation in the GLUD1 gene) [2, 3].”
BackgroundSelf-citationBendix, J., Laursen, M. G., Mortensen, M. B., Melikyan, M. A., Globa, E., Detlefsen, S., Rasmussen, L. M., Petersen, H., Brusgaard, K., & Christesen, H. T. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00478 · Cited by 15 · see citing works
“Furthermore, the laparoscopic approach is dependent on preoperative identification of the focal lesion as predicted by heterozygous paternal KATP-channel mutations and 18F-DOPA-PET/CT (29, 37, 38).”
BackgroundRasmussen, A. G., Melikyan, M. A., Globa, E., Detlefsen, S., Rasmussen, L. M., Petersen, H., Brusgaard, K., Rasmussen, A. H., Mortensen, M. B., & Christesen, H. T. (2020) · Pediatric Diabetes · doi:10.1111/pedi.12989 · Cited by 15 · see citing works
“Median (range), days 3 (1-270) 49 (1-270) 1 (1-120) .”
Paternally inherited ABCC8 mutation causing diffuse congenital hyperinsulinism
Chandran, S., Yap, F. K. P., Rajadurai, V. S., Lu, Y. T., Chang, K. T. E., Flanagan, S. E., Ellard, S., & Hussain, K. (2013) · Endocrinology Diabetes and Metabolism Case Reports · doi:10.1530/edm-13-0041 · Cited by 15 · see citing works
Self-citationMatsutani, N., Furuta, H., Matsuno, S., Oku, Y., Morita, S., Uraki, S., Doi, A., Furuta, M., Iwakura, H., Ariyasu, H., et al. (2019) · Journal of Diabetes Investigation · doi:10.1111/jdi.13138 · Cited by 15 · see citing works
Possible New Strategies for the Treatment of Congenital Hyperinsulinism
Sikimić, J., Hoffmeister, T., Gresch, A., Kaiser, J. K., Barthlen, W., Wolke, C., Wieland, I., Lendeckel, U., Krippeit-Drews, P., Düfer, M., et al. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.545638 · Cited by 15 · see citing works
Sang, Y., Xu, Z., Liu, M., Yan, J., Wu, Y., Zhu, C., & Ni, G.-C. (2014) · Endocrine Journal · doi:10.1507/endocrj.ej13-0398 · Cited by 15 · see citing works
Velde, C. D., Molnes, J., Berland, S., Njølstad, P. R., & Molven, A. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae459 · Cited by 16 · see citing works
Lang, T., & Hussain, K. (2013) · Advances in clinical chemistry · doi:10.1016/b978-0-12-800094-6.00006-6 · Cited by 14 · see citing works
Self-citationCongenital hyperinsulinism: management and outcome, a single tertiary centre experience
Eltonbary, K., Robinson, P. N., Banerjee, I., & Shaikh, M. G. (2020) · European Journal of Pediatrics · doi:10.1007/s00431-020-03581-z · Cited by 14 · see citing works
Hyperinsulinemic Hypoglycemia Diagnosed in Childhood Can Be Monogenic
Hopkins, J. J., Childs, A. J., Houghton, J., Hewat, T. I., Atapattu, N., Johnson, M. B., Patel, K. A., Laver, T. W., & Flanagan, S. E. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac604 · Cited by 13 · see citing works
Self-citationLong-Term Follow-Up and Mutation Analysis of 27 Chinese Cases of Congenital Hyperinsulinism
Su, C., Gong, C., Saenger, P. H., Li, W., Wu, D., Gu, Y., & Cao, B. (2014) · Hormone Research in Paediatrics · doi:10.1159/000356911 · Cited by 13 · see citing works
Xu, A., Cheng, J., Sheng, H., Wen, Z., Lin, Y., Zhou, Z., Zeng, C., Shao, Y., Li, C., Liu, L., et al. (2019) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.galenos.2019.2019.0046 · Cited by 13 · see citing works
“The mutation detection rates of ABCC8 and KCNJ11 genes reported by Kapoor et al (6) and by Snider et al (26) were 36.”
BackgroundResultInfluentialRefinement of the critical genomic region for hypoglycaemia in the Chromosome 9p deletion syndrome
Banerjee, I., Senniappan, S., Laver, T. W., Caswell, R. C., Zenker, M., Mohnike, K. L., Cheetham, T. D., Wakeling, M. N., Ismail, D., Lennerz, B. S., et al. (2019) · Wellcome Open Research · doi:10.12688/wellcomeopenres.15465.1 · Cited by 12 · see citing works
Self-citationBanerjee, I., Senniappan, S., Laver, T. W., Caswell, R. C., Zenker, M., Mohnike, K. L., Cheetham, T. D., Wakeling, M. N., Ismail, D., Lennerz, B. S., et al. (2020) · Wellcome Open Research · doi:10.12688/wellcomeopenres.15465.2 · Cited by 12 · see citing works
Self-citationLaimon, W. N., Aboelenin, H. M., & Tantawi, N. T. E. (2021) · Pediatric Diabetes · doi:10.1111/pedi.13186 · Cited by 12 · see citing works
- Authors
- Kapoor, R. R., Flanagan, S. E., Arya, V. B., Shield, J. P., Ellard, S., & Hussain, K.
- Affiliations
- Great Ormond Street Hospital (GB)
- University of Exeter (GB)
- Corresponding author
- Hussain, Khalid
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-04
- Volume
- 168
- Issue
- 4
- Pages
- 557-564
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- PMC
- PMC3599069
- OpenAlex
- W2111189973
- Semantic Scholar
- 1a21aa2a4c44a96603182b698464b7e013b7884f
- Cited by
- 243
- References
- 81
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 17 · 2023: 19 · 2022: 25 · 2021: 23 · 2020: 21 · 2019: 20 · 2018: 13 · 2017: 12 · 2016: 12 · 2015: 27 · 2014: 22 · 2013: 6
- FWCI
- 22.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- European Journal of Endocrinology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Funders
- Wellcome Trust (081188/A/06/Z)
- Society for Endocrinology
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- congenital hyperinsulinism, ABCC8, KCNJ11, HNF4α, GLUD1, hydroxyacyl-CoA dehydrogenase, glucokinase, MCT1, genetic diagnosis, recessive inheritance, paternal mutations, diffuse hyperinsulinism, hyperammonemia, consanguinity, genotype-phenotype correlation
- MeSH terms
- Kcnj11 Channel, Diazoxide, Female, Humans, Infant, Infant, Newborn, Male, Mutation, Receptors, Drug, Cohort Studies, ATP-Binding Cassette Transporters, Potassium Channels, Inwardly Rectifying, Congenital Hyperinsulinism, Sulfonylurea Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
