Congenital hyperinsulinism

Disease Overview

Congenital hyperinsulinism is a disease where there are abnormally high levels of insulin, a hormone produced by the beta cells of the pancreas that helps control blood sugar levels. Because of the high levels of insulin, people with this disease have frequent episodes of low blood sugar (hypoglycemia) that can even occur after eating. In babies and young children, these episodes are characterized by a lack of energy (lethargy), irritability, or difficulty feeding. Repeated episodes of low blood sugar increase the risk for serious complications such as breathing difficulties, seizures, intellectual disability, vision loss, brain damage, and coma.[4801][14166] The severity and onset of these episodes varies, even among members of the same family. In about 60% of the cases, the episodes start within the first month of life and are very severe and difficult to manage. In other cases, the disease starts in childhood or later, and the symptoms are mild.[14166]  Early diagnosis and treatment is important to prevent neurologic damage from hypoglycemia.[14167]

Congenital hyperinsulinism is caused by mutations in at least 11 different genes, including ABCC8 (responsible for about 45 % of the cases), KCNJ11, GLUD1, GCK, HK1, HADH, HNF4A, HNF1A, SLC16A1, UCP2, and PGM1. Inheritance may be autosomal recessive or autosomal dominant.[4801][14168] Some cases are caused by loss of genetic material in a region of chromosome 11 (11p15) that comes from the mother (maternal chromosome). According to the extent of abnormal beta cells,  the disease can be focal (when abnormal beta cells are limited to 1 or a few areas in the pancreas) and diffuse (where the abnormal beta cells are spread throughout the pancreas).[14168] The goal of treatment is to manage the hypoglycemia to prevent brain damage. Medications may include diazoxide, octreotide, and glucagon.[14169] Surgery to remove part of the pancreas might be required in severe cases.[14167][14168] Genetic testing may help to guide the best treatment.[14168]

Synonyms

• Familial hyperinsulinism
• Congenital isolated hyperinsulinism
• CHI
• Persistent hyperinsulinemic hypoglycemia of infancy
• PHHI
• Hyperinsulinemic hypoglycemia familial
• Hypoglycemia hyperinsulinemic of infancy
• Hyperinsulinism familial with pancreatic nesidioblastosis
• Nesidioblastosis of pancreas
• Hyperinsulinism congenital
• Hyperinsulinemic hypoglycemia due to focal adenomatous hyperplasia