The DOI matches its Crossref record; 102 of the 104 references it cites were found in a registry or an index.
Perspective on the Genetics and Diagnosis of Congenital Hyperinsulinism Disorders
Open accessAbstract
CONTEXT: Congenital hyperinsulinism (HI) is the most common cause of hypoglycemia in children. The risk of permanent brain injury in infants with HI continues to be as high as 25-50% due to delays in diagnosis and inadequate treatment. Congenital HI has been described since the birth of the JCEM under various terms, including "idiopathic hypoglycemia of infancy," "leucine-sensitive hypoglycemia," or "nesidioblastosis." EVIDENCE ACQUISITION: In the past 20 years, it has become apparent that HI is caused by genetic defects in the pathways that regulate pancreatic β-cell insulin secretion. EVIDENCE SYNTHESIS: There are now 11 genes associated with monogenic forms of HI (ABCC8, KCNJ11, GLUD1, GCK, HADH1, UCP2, MCT1, HNF4A, HNF1A, HK1, PGM1), as well as several syndromic genetic forms of HI (eg, Beckwith-Wiedemann, Kabuki, and Turner syndromes). HI is also the cause of hypoglycemia in transitional neonatal hypoglycemia and in persistent hypoglycemia in various groups of high-risk neonates (such as birth asphyxia, small for gestational age birthweight, infant of diabetic mother). Management of HI is one of the most difficult problems faced by pediatric endocrinologists and frequently requires difficult choices, such as near-total pancreatectomy and/or highly intensive care with continuous tube feedings. For 50 years, diazoxide, a KATP channel agonist, has been the primary drug for infants with HI; however, it is ineffective in most cases with mutations of ABCC8 or KCNJ11, which constitute the majority of infants with monogenic HI. CONCLUSIONS: Genetic mutation testing has become standard of care for infants with HI and has proven to be useful not only in projecting prognosis and family counseling, but also in diagnosing infants with surgically curable focal HI lesions. (18)F-fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET scans have been found to be highly accurate for localizing such focal lesions preoperatively. New drugs under investigation provide hope for improving the outcomes of children with HI.
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“While the pathophysiology of persistent hyperinsulinemic hypoglycemia in childhood and infancy, which is morphologically similar to NIPHS, is well understood from a genetic and functional point of view, mechanistic data on adult-onset NIPHS is scarce [49].”
From An Uncommon Cause of Recurrent Presyncope, Dizziness, and Tachycardia: A Case Report of Diffuse, Adult-Onset Nesidioblastosis/Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS) (2023) · cites this paper as [49]
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“Loss-of-function mutations cause congenital hyperinsulinism because they result in permanent membrane depolarization and persistent insulin release (479, 644, 681).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [644]
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Citations
Cites
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Self-citationThornton, P. S., Stanley, C. A., De Leon, D. D., Harris, D., Haymond, M. W., Hussain, K., Levitsky, L. L., Murad, M. H., Rozance, P. J., Simmons, R. A., et al. (2015) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2015.03.057 · Cited by 625 · cited 2×
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BackgroundSelf-citationFamilial Hyperinsulinism Caused by an Activating Glucokinase Mutation
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Cited by
Sorted by citations
Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793
Mechanisms controlling pancreatic islet cell function in insulin secretion
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Therapies and outcomes of congenital hyperinsulinism‐induced hypoglycaemia
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ATP‐Sensitive Potassium Channels and Their Physiological and Pathophysiological Roles
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“In severe diffuse disease, partial pancreatectomy is ultimately necessary and may in later life lead to diabetes mellitus (502).”
New insights into KATP channel gene mutations and neonatal diabetes mellitus
Pipatpolkai, T., Usher, S., Stansfeld, P. J., & Ashcroft, F. M. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0351-y · Cited by 122
Metadata
- Authors
- Stanley, C. A.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Stanley, Charles A.
- ORCID
- Stanley, Charles A.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2016-03
- Volume
- 101
- Issue
- 3
- Pages
- 815-826
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC4803157
- OpenAlex
- W2277559429
- Cited by
- 239
- References
- 104
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 13 · 2023: 13 · 2022: 24 · 2021: 25 · 2020: 36 · 2019: 24 · 2018: 39 · 2017: 25 · 2016: 13
- FWCI
- 6.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Children's Hospital of Philadelphia
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK056268)
- 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 › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- congenital hyperinsulinism, pancreatic beta-cell insulin secretion, ABCC8, KCNJ11, genetic diagnosis, diazoxide, near-total pancreatectomy, 18F-DOPA PET, focal pancreatic lesions, Beckwith-Wiedemann syndrome, Kabuki syndrome, Turner syndrome, neonatal hypoglycemia
- MeSH terms
- Insulin Secretion, Humans, Infant, Newborn, Insulin, Congenital Hyperinsulinism, KATP Channels
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