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Primary Care

Presentation: Patient with young-onset diabetes and an affected parent: HNF4A MODY

A patient with early onset diabetes and an affected parent may have an underlying genetic condition known as maturity-onset diabetes of the young, which can have implications for their diabetes management.

At a glance:

  • A patient with early onset diabetes and an affected parent could have maturity-onset diabetes of the young (MODY). Genomic testing (if the patient meets the criteria for genomic testing) could identify a pathogenic variant in the HNF4A gene.
  • Individuals who inherit a variant in the HNF4A gene often have a high birth weight (over 4kg) and may have needed treatment for low blood sugars early in life (neonatal hypoglycaemia).
  • HNF4A MODY is best treated with low doses of sulphonylureas. However, with increasing age, individuals may require a combination of tablets and other medication, in some cases including insulin, to stop deterioration in blood glucose.
  • Alert! Those with HNF4A MODY have a 50% chance of having an affected child, who will be at risk of macrosomia and transient neonatal hypoglycaemia due to hyperinsulinism. This can alter monitoring and testing options during pregnancy, and it is therefore important to seek specialist advice from the Exeter Clinical Laboratory.

Example clinical scenario

A 48-year-old man transfers to your care having recently moved into the area. He was diagnosed with diabetes at 28 years of age and has been treated with tablets ever since. His BMI is 25. His mother had diabetes and was also treated with tablets. His first child was born at term with a birth weight of 3.6kg and no problems. His second child was born at 38 weeks’ gestation with a birth weight of 4.2kg and had transient neonatal hyperinsulinaemic hypoglycaemia, which required treatment with diazoxide for six months.

Identifying those at risk of a genetic condition

  • Flags for an underlying genetic diagnosis of HNF4A MODY include:
    • diagnosis of diabetes below the age of 25 in an individual with a parent or child with a diagnosis of diabetes;
    • sensitivity to sulphonylureas; and
    • having a child who is born with macrosomia and neonatal hypoglycaemia or having a history of it as a newborn with a parent who has diabetes.
  • HNF4A MODY typically results in diabetes presenting in adolescence or early adulthood, although some people may not be diagnosed until middle or old age.
  • HNF4A MODY follows an autosomal dominant inheritance pattern, meaning that first-degree relatives have a 50% chance of being affected. This means that diabetes is usually identified in two or more generations.
  • Individuals with HNF4A MODY may be sensitive to sulphonylureas, although as the diabetes progresses additional medication may be needed. Those with HNF4A MODY taking insulin from diagnosis of diabetes prior to genomic testing may be able to stop insulin and convert to sulphonylurea tablet treatment instead.
  • HNF4A MODY can lead to macrosomia and neonatal hypoglycaemia in affected babies, so specialist advice is required during pregnancy (irrespective of whether the mother or father has a pathogenic HNF4A variant) and non-invasive prenatal genomic testing (NIPT) using cell-free fetal DNA (cffDNA) to aid management may be possible.

What do you need to do?

Resources

For clinicians

References:

For patients

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  • Last reviewed: 09/05/2025
  • Next review due: 09/05/2026
  • Authors: Professor Maggie Shepherd
  • Reviewers: Dr Maarit Brooks, Professor Kevin Colclough, Dr Asma Hamad

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