2.1. Maturity-Onset Diabetes of the Young

Mutations in the HNF4A gene cause maturity-onset diabetes of the young (MODY), which is a group of conditions characterized by abnormally high blood sugar levels. MODY usually begins before age 30. HNF4A gene mutations cause a type called HNF4A-MODY (also known as MODY1). Often babies with this condition are heavier than average when they are born, and they may have unusually low blood sugar levels. Symptoms of high blood sugar, which usually begin in childhood or early adulthood, include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, weight loss, and recurrent skin infections. Over time, uncontrolled high blood sugar can lead to eye and kidney problems.

HNF4A gene mutations result in production of an altered HNF-4α protein that is unable to function normally. Some changes prevent the HNF-4α protein from forming dimers; others prevent the attachment of additional proteins that aid in transcription; still others prevent the transcription factor from attaching to DNA to control gene activity. These changes interrupt transcription, altering gene activity in cells. As a result, beta cell development and function are impaired. The cells are less able than normal to produce insulin in response to sugar in the blood, which means blood sugar cannot be controlled. Elevated blood sugar results in the signs and symptoms of MODY