MODY1

MODY1, short for maturity-onset diabetes of the young type 1, is a form of monogenic diabetes caused by mutations in the gene that encodes hepatocyte nuclear factor 4 alpha (HNF4A). It is inherited in an autosomal dominant pattern and typically presents in adolescence or early adulthood with progressive beta-cell dysfunction leading to hyperglycemia. Patients often have a family history of diabetes across generations and may be non-obese. Endogenous insulin production is reduced, and autoimmunity is not a feature.

Diagnosis is suspected in young individuals with persistent hyperglycemia, a strong family history, and preserved or variable C-peptide levels, after autoimmune diabetes has been excluded. Confirmation is achieved through genetic testing for MODY-related mutations, including HNF4A.

Management considerations for MODY1 center on preserving insulin secretion and achieving good glycemic control. Many individuals respond to low-dose oral sulfonylureas, which stimulate residual beta-cell function, though some may require insulin therapy as the disease progresses or if beta-cell reserve declines. Treatment is individualized based on glucose measurements, tolerance, and presence of any complications. Pregnancy planning may require particular attention due to effects on both mother and fetus.

Genetics and counseling: because MODY1 is autosomal dominant, each child of an affected parent has a 50% chance of inheriting the mutation. Genetic counseling is recommended for affected individuals and their families. In pregnancies where the mother carries an HNF4A mutation, newborns may face neonatal complications such as macrosomia and hypoglycemia related to maternal hyperglycemia.