The DOI matches its Crossref record; 81 of the 81 references it cites were found in a registry or an index.
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.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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.
Citations
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
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 698
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
Thomas, P. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.11.1809 · Cited by 443
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 436
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
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
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
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
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
Research works printed but not linked: 1
- 2004, Molecular genetics and metabolism, 81, S45
Cited by
Sorted by citations
Items 201–240 of 240
Karlekar, M. P., Sarathi, V., Arya, S., Flanagan, S. E., Patil, V. A., Lila, A. R., Shah, N. S., & Bandgar, T. (2021) · Hormone and Metabolic Research · doi:10.1055/a-1654-8542 · Cited by 1
“Other mutations are in the genes maintaining the intracellular concentration of signaling (ATP/ADP)/intermediary molecules which trigger insulin release, for example, GLUD1, HADH, GCK, HNF4A, which account for~20 % of diazoxide-responsive CHI [3].”
BackgroundSelf-citationSukhotskaya, A. A., Bairov, V. G., Mitrofanova, L. B., Перминова, А. А., Rijkova, D. V., Nikitina, I. L., Азимхоновна, А. С., & Каганцов, И. М. (2022) · Russian Journal of Pediatric Surgery Anesthesia and Intensive Care · doi:10.17816/psaic1221 · Cited by 1
“На сегодняшний день описано 16 генов, которые играют ключевую роль в регуляции секреции инсулина (ABCC8, KCNJ11, KCNQ1, GLUD1, GCK, HADH1, SLC16A1, UCP2, HNF1A, HNF4A, HK1, PGM1, PMM2, FOXA2, CACNA1D и EIF2S3), однако около 40 % пациентов не имеют дефектов в указанных генах [5]; дальнейшее изучение генов продолжается.”
Gündoğdu, S., ÇİFTÇİ, M., Atay, E., Ayaz, A., Ceran, Ö., & Atay, Z. (2022) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2022-0155 · Cited by 1
Buraczewska, M., Brandt, A., Sykut‐Cegielska, J., Barg, E., & Borowiec, M. (2015)
Warncke, K., Falco, F., Rabl, W., Engelsberger, I., Saier, J., Flores-Rodriguez, D., Burdach, S. E. G., & Bonfig, W. (2016) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2016-0103
Next-Generation Sequencing for the Diagnosis of Monogenic Disorders of Insulin Secretion
Johnson, A. E. K., Greeley, S. A. W., & del Gaudio, D. (2017) · Springer eBooks · doi:10.1007/978-3-319-56418-0_11
A Neonatal Case of Congenital Hyperinsulinism Due to Homozygous KCNJ11 Gene Mutation
Demirol, H. A., Olukman, Ö., Nalbantoğlu, Ö., Çelik, K., Çolak, R., & Çalkavur, Ş. (2017) · The Anatolian Journal of General Medical Research · doi:10.5222/terh.2017.163
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) · UCL Discovery (University College London)
Self-citationMolecular Diagnosis of Congenital Hyperinsulinism
Flanagan, S. E., Boodhansingh, K. E., Lalonde, E., & Ganguly, A. A. (2019) · Contemporary Endocrinology · doi:10.1007/978-3-030-02961-6_5
Self-citationKempler, M., Baló, T., Varga, É., Barkai, L. J., Körner, A., Pánczél, P., & Hosszúfalusi, N. (2019) · Diabetologia Hungarica · doi:10.24121/dh.2019.6
Erbaş, İ. M., Çatlı, G., Paketçi, A., Anık, A., Demir, K., Böber, E., & Abacı, A. (2020) · Güncel Pediatri · doi:10.4274/jcp.2020.0029
Longo, G. (2022) · Medico e Bambino · doi:10.53126/meb41063
Ipoglicemia in un neonato e iperinsulinismo
Risso, F. M., & Tornese, G. (2022) · Medico e Bambino · doi:10.53126/meb41057
Chroustová, D., Trnka, J., Pudlač, A., Obermannová, B., & Lambert, L. (2020) · Revista Española de Medicina Nuclear e Imagen Molecular (English Edition) · doi:10.1016/j.remnie.2020.07.001
Casertano, A., Frisso, G., Montefusco, G., Mazzaccara, C., Villani, G. R. D., Mozzillo, E., Ruoppolo, M., & Franzese, A. (2019) · Gazzetta Medica Italiana Archivio per le Scienze Mediche · doi:10.23736/s0393-3660.18.03884-6
Kongenitaler Hyperinsulinismus
Rami-Merhar, B. M. (2021) · Journal für Klinische Endokrinologie und Stoffwechsel · doi:10.1007/s41969-021-00146-9
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.2019.0046
Arnoux, J., & de Lonlay, P. (2016) · Springer eBooks · doi:10.1007/978-3-662-49771-5_9
(2022) · American Registry of PathologyArlington, Virginia eBooks · doi:10.55418/9781933477251-5
Su, H., Chen, L., Yang, G., Wang, D.-Q., Li, X.-N., Song, Y., & Gui-FangCao (2023) · Indian Journal of Animal Research · doi:10.18805/ijar.bf-1599
Open and laparoscopic resections of the pancreas in congenital hyperinsulinism
Sukhotskaya, A. A., Bairov, V. G., Каганцов, И. М., Nikitina, I. L., Mitrofanova, L. B., Перминова, А. А., Рыжкова, Д. В., & Malysheva, D. A. (2023) · Endoscopic Surgery · doi:10.17116/endoskop20232905115
Congenital Hyperinsulinism - Two Decades of Specialized Care in a Tertiary Pediatric Hospital
Gonçalves, C. F., Goncalves, C. O., Costa, C., Neves, R., Piña, R., Diamantino, C., Fitas, A. L., Galhardo, J., Limbert, C., & Lopes, L. (2024) · Pediatric Oncall · doi:10.7199/ped.oncall.2025.19
Stars and Rising Stars in Pediatric Endocrinology: 2022
(2024) · Frontiers research topics · doi:10.3389/978-2-8325-4686-4
Glucose Dysregulation Associated with Hypoglycaemia in Childhood and Adolescence
Güemes, M., & Shah, P. (2024) · Endocrinology · doi:10.1007/978-3-030-18901-3_11-1
Zukeran, H., Akiba, K., Higuchi, S., Mori, J., Yorifuji, T., & Hasegawa, Y. (2024) · Clinical Pediatric Endocrinology · doi:10.1297/cpe.2023-0086
“2, which constitute the ATP-sensitive potassium (KATP) channel on the β -cell plasma membrane (3, 4).”
BackgroundGlucose Dysregulation Associated with Hypoglycemia in Childhood and Adolescence
Güemes, M., & Shah, P. (2024) · Endocrinology · doi:10.1007/978-3-030-23709-7_11
Congenital hyperinsulinemic hypoglycaemia in a neonate: a rare homozygous ABCC8 gene mutation
Prabha, C., Tripathi, S., Bhriguvanshi, A., & Kumar, M. (2025) · BMJ Case Reports · doi:10.1136/bcr-2024-264778
Ghrelin and relamorelin alleviate hypoglycaemia in humanised mice with congenital hyperinsulinismPreprint
Lithovius, V., Montaser, H., Saarimäki-Vire, J., Ibrahim, H., Barsby, T., Balboa, D., & Otonkoski, T. (2025) · bioRxiv · doi:10.1101/2025.10.02.680116
Additional file 1 of An expanded clinical spectrum of hypoinsulinaemic hypoketotic hypoglycaemia
Welters, A., Leiter, S. M., Bachmann, N., Bergmann, C., Hoermann, H., Korsch, E., Meissner, T., Payne, F., Williams, R. M., Hussain, K., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24580415
Self-citationCongenital hyperinsulinism in an individual with CHARGE syndrome and a pathogenic CHD7 variant
Ibeas, C., Giraudo, F., Männistö, J. M. E., Flanagan, S. E., & Verónica Mericq, G. (2026) · JCEM Case Reports · doi:10.1210/jcemcr/luag016
“While it is recognized that up to 50% of children with persistent HI may not have a genetic diagnosis following routine screening [15], the absence of a disease-causing variant in the 22 genes tested lends support that the CHARGE syndrome and HI in our patient are likely to be related rather than…”
Self-citationPancreatectomy Outcomes in Pediatric Hyperinsulinism: A Retrospective Single-Center Experience
Özaydın, S., Coskun, N., Özaydın, İ. Y., & Çöloğlu, Ö. (2026) · Journal of Surgical Research · doi:10.1016/j.jss.2026.02.002
Diagnostik und Therapie des kongenitalen Hyperinsulinismus (KHI)
MEISSNER, T., Blankenstein, O., LINDNER, M., & SANTNER, M. (2025) · Elsevier eBooks · doi:10.1016/b978-3-437-21447-9.50072-6
Expanding the genetic burden of low-evidence genes in pulmonary arterial hypertension
Miranda-Alcaraz, L., Mora‐Gómez, M., Gallego, N., Cruz‐Utrilla, A., Marín, M. J. D. C., Parra, N. O., de Miguel, I. M., Ortiz, E. G., Jiménez-Estrada, J. A., Parra, A., et al. (2026) · European Journal of Human Genetics · doi:10.1038/s41431-026-02081-2
“Regarding transporter and channel genes, ABCC8 encodes the protein SUR1 (Sulfonylurea receptor-1), a regulator of ATP-sensitive potassium channels, which is associated with diseases such as type II diabetes and congenital hyperinsulinism [11 – 13].”
Derhourhi, M. (2018) · theses.fr (ABES) · doi:10.70675/2d396fe9z564dz48a1z89b4z746f99df764e
Focal congenital hyperinsulinism: spontaneous glycemic improvement before surgery
Arnoux, J., Mayer, C., Jhaouat, I., Saint‐Martin, C., Bérat, C., Altenburger, L., Brassier, A., Bouchereau, J., Querciagrossa, S., Bustarret, O., et al. (2026) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgag227
Sharifi, F., Abdolahpour, S., Setoudeh, A., Abbasi, F., Mirzaee, H. S., Sayarifard, A., Mohsenipour, R., & Rostami, P. (2026) · Hormone Research in Paediatrics · doi:10.1159/000553031
Stafford-Bell, A., Hooper, A. J., Romans, R., Flavel, R., Rao, S. C., Choong, C. S., Flanagan, S. E., & Abraham, M. B. (2026) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2026-0122
“Although previous studies reported a genetic diagnosis in only approximately 50 % of cases using ABCC8 and KCNJ11 testing alone [5, 29], more recent studies report an aetiology (isolated genetic CHI and syndromic CHI) in 65 – 86 % of the cohort [28, 30, 31].”
Self-citationLithovius, V., Montaser, H., Saarimäki‐Vire, J., Ibrahim, H., Barsby, T., Balboa, D., & Otonkoski, T. (2026) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szag055
Congenital Hyperinsulinism with Paternally Inherited ABCC8 Variants
Chua, C., Chan, D., Koh, A. L., Chandran, S., & Yap, F. K. P. (2026) · Journal of the ASEAN Federation of Endocrine Societies · doi:10.15605/jafes.041.02.6197
“10 While majority of the diazoxide-responsive cases had no identifiable mutation, 92.8% of those unresponsive to diazoxide had either ABCC8 or KCNJ11 pathogenic variants.”
InfluentialContractor, J. B., Bharti, L., Shah, I., Shah, S., Nimbalkar, S. M., Bajpai, A., Kumar, R., Mohan, V., Venkatesan, R., & Shah, P. (2026) · Children · doi:10.3390/children13101431
“Functional consequences of individual variants, rather than inheritance pattern alone, frequently determine disease expression, highlighting the complexity of genotype–phenotype relationships [10,11,17,28,33].”
Influential
Metadata
- 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 › Endocrinology, Diabetes and Metabolism › 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
