Back Print

Diabetes – Monogenic Diabetes

Also known as: Neonatal diabetes, Familial Diabetes

Background

Monogenic diabetes (diabetes caused by a genetic change in a single gene) affects approximately 2 per cent of cases of diabetes in the UK.

The majority of cases of monogenic diabetes are initially misdiagnosed as type 1 or type 2 diabetes. However, genetic testing can be used to accurately diagnose monogenic types of diabetes. This is important as it can predict how the person may be affected by their condition, explains other symptoms, guides appropriate treatment and enables genetic counselling of family members. Many patients with a confirmed genetic cause for their diabetes have been able to stop insulin injections and achieve better blood glucose control on tablet treatments.

Credits

Medical text written February 2013 by Dr M Shepherd, Senior Clinical Research Fellow, Royal Devon and Exeter NHS Foundation Trust and Honorary Reader, University of Exeter Medical School, UK.

Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information is provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.

This entry is pending review, and certain details may no longer be up to date. Please ring our helpline or email our Rare Conditions Information Officer for more information.

Types of monogenic diabetes

  • Neonatal diabetes - diabetes is diagnosed before six months of age.
  • Familial diabetes - (also known as maturity onset diabetes of the young or MODY).

Neonatal diabetes
This type of diabetes is diagnosed within the first six months of life. It may last for a short time then resolve but return again, typically during the teenage years, or be permanent. The features of the condition include low birth weight, undetectable pancreatic autoantibodies (proteins made by the immune system which attacks the body's own tissue) and marked hyperglycaemia (high levels of glucose in the blood) at diagnosis.

Around 50 to 60 per cent of those with permanent neonatal diabetes have been identified with changes in one of the potassium channel genes (Kir6.2 or SUR1), which affects insulin production. Ninety per cent of these patients have been able to stop insulin treatment and transfer to high doses of sulphonylurea tablets which enables their body to secrete their own insulin and therefore better control the glucose level in their blood. Twenty per cent of patients with changes in Kir6.2 or SUR1 also have neurological features such as delayed development (see entry Global Developmental Delay) and epilepsy which is associated with their diabetes.

Familial diabetes (MODY)
MODY is passed down from an affected member in one generation to the next (it is inherited). The change in the gene is inherited from an affected parent, therefore diabetes is present in two or more generations. Each child has a 50 per cent chance of inheriting the affected gene from their parent with MODY and if they inherit the affected gene their lifetime risk of developing diabetes is greater than 99 per cent. Familial diabetes is typically diagnosed before 25 years of age in at least one family member. People with MODY continue to make insulin of their own, but due to the young age of diagnosis are often mistaken to have Type 1 diabetes and unnecessary started on insulin.

HNF1A
HNF1A accounts for 60 per cent of UK MODY. Additional features include a low level at which the kidneys allow glucose into the urine (renal threshold) and sulphonylurea sensitivity. Patients with HNF1A diabetes are known to be particularly sensitive to tablets called sulphonylureas, which help the body produce more insulin and this is considered the most appropriate form of treatment for this group. Annual screening for complications is advisable. HNF1A diabetes is progressive, gets worse over time, and although HNF1A diabetes can often be managed with sulphonylurea tablets for many years, the addition of insulin may be required in middle/later life.

HNF4A
HNF4A is rarer than HNF1A, but has similar features although age of diagnosis of diabetes may be later. Those affected tend to have high birth weight (above 4kg/9lb) and may have low blood glucose shortly after birth, which may require treatment. Patients with HNF4A can also be managed on sulphonylurea tablets for many years.

GCK
GCK accounts for 22 per cent of UK MODY. It is characterised by mild, stable raised blood glucose throughout life. The condition is often detected by routine screening. No treatment is required and complications are rare.

HNF1B
In HNF1B MODY, renal (kidney) cysts (or other kidney problems) are often present and may be detected during antenatal ultrasound. Gout can also occur. Diabetes may become apparent after the renal problems. This condition usually requires treatment with insulin.

How is it diagnosed?

Diagnostic genetic testing for patients thought to have monogenic diabetes is available at the Royal Devon and Exeter Hospital which is the UK referral centre for monogenic diabetes. This may confirm the diagnosis and the specific subtype which allows specific decisions regarding treatment to be made, such as the use of a sulphonylurea in those with HNF1A. It also allows guidelines to be given about the likely clinical course of the diabetes.

In families where monogenic diabetes has been confirmed by genetic testing, a predictive genetic test may be offered to those family members who have shown no signs of diabetes. This would reveal whether they have inherited normal copies of the gene and have the same chance of developing diabetes as the general population or whether they have inherited an affected gene, and therefore will go on to develop diabetes.

Further information regarding monogenic diabetes and genetic testing may be obtained from www.diabetesgenes.org, which is run by the Department of Diabetes and the Centre for Molecular Genetics at the University of Exeter Medical School and Royal Devon and Exeter NHS Foundation Trust Hospital, Exeter, UK.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Affected families should seek advice and support from a genetic centre who can give individualised information.

Prenatal diagnosis
This may be possible. Affected families should seek individual advice.

Is there support?

Information and support in the UK for monogenic diabetes is provided by Diabetes UK (see entry Diabetes Mellitus).