Mody 3E11.-

MODY is the acronym for "Maturity-onset Diabetes of the Young" and describes a group of autosomal-dominantly inherited, genetically heterogeneous, not always insulin-dependent forms of diabetes. The MODY forms of diabetes are caused by various disorders of beta cell function in the pancreas. The body weight of MODY patients is usually normal. Neither are any of the autoimmune phenomena characteristic of type 1 diabetes observed. Rare are other associated organ dysplasias (eyes, pancreas, intestine). MODY-3 affects 69% of all MODY cases and is therefore the most common MODY variation.

MODY 3 is triggered by autosomal dominant inherited mutations in the HNF1A gene located on the long arm of chromosome 12 (12q24.31). The HNF1A gene encodes the transcription factor HNF1alpha, which regulates the transcription of genes involved in insulin production and secretion in pancreatic beta cells. If mutations in the HNF1A gene are present, pathologically reduced insulin production occurs. MODY3 diabetes is one of the most common forms of MODY, accounting for about 60% of all cases. In about 8% of MODY cases "de novo" mutations occur for the first time in the family.

The clinical picture is similar to MODY1 diabetes. About 8-9% of < 30-year-old MODY patients are not slim but overweight. After an initially often mild course, the diabetes progresses continuously over time. Many of the patients require therapy with oral antidiabetics. About 30-40% have to be adjusted to insulin during their life. Those affected develop the full range of late complications of diabetes.

Especially slim pregnant women with glucose tolerance disorders are highly likely to be carriers of a GCK gene mutation (see MODY 2) or a HNF4A gene mutation (see MODY 1). Pregnant women with gestational diabetes and a mutation in the HNF1A gene have a particularly high risk of developing fetal hyperinsulinism in their child (even without a fetal mutation of the HNF1 gene present). The consequences of this hyperinsulinism can be strong fetal growth during pregnancy and high fetal weight at birth (macrosomia). Therefore, knowledge of a carrier for an HNF1A mutation of the mother (and possibly also of the child) is therefore very important in order to prepare for the birth through optimal management.

Indication for genetic analysis:

• Manifestation age of diabetes in early adolescence
• No GAD and/or IA2 antibodies (exclusion of type 1 diabetes)
• Positive family history, autosomal dominant inheritance
• Diabetes without obesity
• Progressive hyperglycaemia in old age
• Gestational diabetes
• No insulin resistance