Familiar hyperinsulinism (ABCC8-related)
Congenital hyperinsulinism is a severe disease of very early manifestation, characterized mainly by elevated blood insulin levels resulting in severe hypoglycemia. Repeated episodes of hypoglycemia increase the risk of complications such as respiratory distress, seizures and neurological damage.
Most cases of congenital hyperinsulinism are caused by the presence of pathogenic variants in the ABCC8 and KCNJ11 genes. Specifically, mutations present in the ABCC8 gene are responsible for 50-60% of cases. Pathogenic variants in these genes affect the release of insulin by pancreatic cells, thereby increasing the secretion of the hormone and its levels in the blood. Excess insulin causes a drop in glucose that ends in hypoglycemia.
The incidence of congenital hyperinsulinism varies between countries, but is generally between 1 case per 27,000 and 1 case per 50,000 population.
Symptoms
The first symptoms have an early onset, and may even appear before birth, and are characterized by sustained hypoglycemia requiring high glucose intakes. Severe uncontrolled hypoglycemia can lead to other symptoms such as lethargy, hypotonia, tremor, irritability or apnea, which can produce important neurological sequelae.
Disease management
Treatment should be early and its main objective is to control blood glucose levels in order to avoid irreversible neurological damage. Initial treatment consists of immediate intravenous glucose administration to maintain stable levels.
In the long term there are various pharmacological treatments such as diazoxide, somatostatin hormone analogues, glucagon, glucocorticoids, among others. Sometimes it is necessary to resort to total or partial pancreatectomy.
Patients should avoid prolonged fasting and eat frequently foods rich in carbohydrates.
Genes analyzed
Bibliography
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Donath X, Saint-Martin C, Dubois-Laforgue D, et al . Next-generation sequencing identifies monogenic diabetes in 16% of patients with late adolescence/adult-onset diabetes selected on a clinical basis: a cross-sectional analysis. BMC Med. 2019 Jul 11;17(1):132.
Gillis D. Familial Hyperinsulinism. 2003 Aug 19 [updated 2019 Mar 21]. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022.
Huopio H, Otonkoski T, Vauhkonen I, et al. A new subtype of autosomal dominant diabetes attributable to a mutation in the gene for sulfonylurea receptor 1. Lancet. 2003 Jan 25;361(9354):301-7.
Männistö JME, Jääskeläinen J, Otonkoski T, et al . Long-Term Outcome and Treatment in Persistent and Transient Congenital Hyperinsulinism: A Finnish Population-Based Study. J Clin Endocrinol Metab. 2021 Mar 25;106(4):e1542-e1551.
Rosenfeld E, Ganguly A, De Leon DD. Congenital hyperinsulinism disorders: genetic and clinical characteristics. Am J Med Genet C Semin Med Genet. 2019 Dec;181(4):682-692.
