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Congenital hyperinsulinism: recent updates on molecular mechanisms, diagnosis and management

  • Dinesh Giri , Katherine Hawton ORCID logo and Senthil Senniappan EMAIL logo
Published/Copyright: September 21, 2021
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 35 Issue 3

Abstract

Congenital hyperinsulinism (CHI) is a rare disease characterized by an unregulated insulin release, leading to hypoglycaemia. It is the most frequent cause of persistent and severe hypoglycaemia in the neonatal period and early childhood. Mutations in 16 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, KCNQ1, CACNA1D, FOXA2, EIF2S3, PGM1 and PMM2) that are involved in regulating the insulin secretion from pancreatic β-cells have been described to be responsible for the underlying molecular mechanisms of CHI. CHI can also be associated with specific syndromes and can be secondary to intrauterine growth restriction (IUGR), maternal diabetes, birth asphyxia, etc. It is important to diagnose and promptly initiate appropriate management as untreated hypoglycaemia can be associated with significant neurodisability. CHI can be histopathologically classified into diffuse, focal and atypical forms. Advances in molecular genetics, imaging techniques (18F-fluoro-l-dihydroxyphenylalanine positron emission tomography/computed tomography scanning), novel medical therapies and surgical advances (laparoscopic pancreatectomy) have changed the management and improved the outcome of patients with CHI. This review article provides an overview of the background, clinical presentation, diagnosis, molecular genetics and therapy for children with different forms of CHI.

Keywords: hyperinsulinism; hypoglycaemia; insulin dysregulation
Corresponding author: Dr. Senthil Senniappan, MD FRCPCH, MSc (Diab), PhD, Consultant Paediatric Endocrinologist & Honorary Associate Professor, Alder Hey Children's Hospital NHS Foundation Trust, Liverpool L14 5AB, UK, Phone: +441512525281, Fax: +441512824606, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

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Received: 2021-06-02
Accepted: 2021-08-30
Published Online: 2021-09-21
Published in Print: 2022-03-28

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Review Article
  3. Congenital hyperinsulinism: recent updates on molecular mechanisms, diagnosis and management
  4. Original Articles
  5. Weight changes of children in 1 year during COVID-19 pandemic
  6. Three novel mutations of the BCKDHA, BCKDHB and DBT genes in Chinese children with maple syrup urine disease
  7. Rates of adrenal insufficiency using a monoclonal vs. polyclonal cortisol assay
  8. Hyperinsulinemic hypoglycemia in growth restricted convalescent preterm neonates: clinical characteristics and impediments to early diagnosis
  9. Identification of three novel pathogenic mutations in cystathionine beta-synthase gene of Pakistani intellectually disabled patients
  10. The prevalence of incidental finding of gynecomastia on thoracic computed tomography in the pediatric age group
  11. The prevalence of hypertension and elevated blood pressure and its correlation with overweight/obesity among students aged 6–17 years in Suzhou
  12. Investigation of androgen receptor gene CAG repeat length polymorphism in pubertal gynecomastia
  13. A single-centre study of genetic mutations, audiology, echocardiogram and pulmonary function in Saudi children with osteogenesis imperfecta
  14. A 10-year retrospective single-center study of alpha-fetoprotein and beta-human chorionic gonadotropin in Romanian children with (para)gonadal tumors and cysts
  15. Clinical, pathological and molecular spectrum of patients with glycogen storage diseases in Pakistan
  16. Allelic dropout in PAH affecting the results of genetic diagnosis in phenylketonuria
  17. Short Communication
  18. Role of the SARS-CoV-2 virus in the appearance of new onset type 1 diabetes mellitus in children in Gran Canaria, Spain
  19. Case Reports
  20. 3-M syndrome – a primordial short stature disorder with novel CUL7 mutation in two Indian patients
  21. The coincidence of two rare diseases with opposite metabolic phenotype: a child with congenital hyperinsulinism and Bloom syndrome
  22. Growth hormone deficiency in a child with benign hereditary chorea caused by a de novo mutation of the TITF1/NKX2-1 gene
  23. Identification of a novel mutation in the PHKA2 gene in a child with liver cirrhosis
https://doi.org/10.1515/jpem-2021-0369
Keywords for this article
hyperinsulinism; hypoglycaemia; insulin dysregulation

Articles in the same Issue

  1. Frontmatter
  2. Review Article
  3. Congenital hyperinsulinism: recent updates on molecular mechanisms, diagnosis and management
  4. Original Articles
  5. Weight changes of children in 1 year during COVID-19 pandemic
  6. Three novel mutations of the BCKDHA, BCKDHB and DBT genes in Chinese children with maple syrup urine disease
  7. Rates of adrenal insufficiency using a monoclonal vs. polyclonal cortisol assay
  8. Hyperinsulinemic hypoglycemia in growth restricted convalescent preterm neonates: clinical characteristics and impediments to early diagnosis
  9. Identification of three novel pathogenic mutations in cystathionine beta-synthase gene of Pakistani intellectually disabled patients
  10. The prevalence of incidental finding of gynecomastia on thoracic computed tomography in the pediatric age group
  11. The prevalence of hypertension and elevated blood pressure and its correlation with overweight/obesity among students aged 6–17 years in Suzhou
  12. Investigation of androgen receptor gene CAG repeat length polymorphism in pubertal gynecomastia
  13. A single-centre study of genetic mutations, audiology, echocardiogram and pulmonary function in Saudi children with osteogenesis imperfecta
  14. A 10-year retrospective single-center study of alpha-fetoprotein and beta-human chorionic gonadotropin in Romanian children with (para)gonadal tumors and cysts
  15. Clinical, pathological and molecular spectrum of patients with glycogen storage diseases in Pakistan
  16. Allelic dropout in PAH affecting the results of genetic diagnosis in phenylketonuria
  17. Short Communication
  18. Role of the SARS-CoV-2 virus in the appearance of new onset type 1 diabetes mellitus in children in Gran Canaria, Spain
  19. Case Reports
  20. 3-M syndrome – a primordial short stature disorder with novel CUL7 mutation in two Indian patients
  21. The coincidence of two rare diseases with opposite metabolic phenotype: a child with congenital hyperinsulinism and Bloom syndrome
  22. Growth hormone deficiency in a child with benign hereditary chorea caused by a de novo mutation of the TITF1/NKX2-1 gene
  23. Identification of a novel mutation in the PHKA2 gene in a child with liver cirrhosis
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