Autosomal dominant hyperinsulinism due to SUR1 deficiency

Autosomal dominant hyperinsulinism due to SUR1 deficiency is a rare genetic form of congenital hyperinsulinism (CHI) caused by heterozygous mutations in the ABCC8 gene, which encodes the sulfonylurea receptor 1 (SUR1) subunit of the ATP-sensitive potassium (KATP) channel in pancreatic beta cells. Unlike the more severe autosomal recessive forms of SUR1-related hyperinsulinism, the dominant form typically presents with a milder phenotype, though it still results in inappropriate and excessive insulin secretion from the pancreas, leading to recurrent episodes of hypoglycemia (low blood sugar). The condition primarily affects the endocrine system, specifically the insulin-regulating mechanisms of the pancreatic beta cells. Key clinical features include recurrent hypoglycemia that may present in the neonatal period, infancy, or later in childhood, and in some cases may not be recognized until adulthood. Symptoms of hypoglycemia include seizures, lethargy, poor feeding, irritability, tremors, and in severe or prolonged cases, developmental delay or brain injury due to neuroglycopenia. The severity is variable, even within the same family carrying the same mutation, ranging from mild, diet-responsive hypoglycemia to more significant disease requiring medical intervention. Treatment options include dietary management with frequent feeds and complex carbohydrates, as well as pharmacological therapy. Diazoxide, which acts on the KATP channel, is often the first-line medical treatment and may be effective in many patients with dominant ABCC8 mutations, in contrast to recessive forms where diazoxide resistance is common. Octreotide (a somatostatin analog) may be used in diazoxide-unresponsive cases. Unlike the diffuse recessive form, near-total pancreatectomy is rarely required in the dominant form. Long-term follow-up is important as some patients may experience resolution of hypoglycemia over time, while others may develop glucose intolerance or diabetes mellitus later in life.

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