Monogenic diabetes is a form of diabetes caused by a mutation of a single gene. The genetic mutation causes the pancreatic beta cells to function abnormally. As a result, the body becomes unable to make sufficient insulin. In some cases insulin resistance develops.
Over 20 specific gene mutations have been identified as causes of different types of monogenic diabetes. These are grouped in two main forms:
- Neonatal diabetes mellitus (NDM) occurs in newborns and young infants. It typically appears in the first six months of life. It can be a transient condition, disappearing within the first year (with a chance of returning later in life), or a permanent, lifelong disease.
- Maturity-onset diabetes of the young (MODY) usually appears in adolescence or early adulthood.
Most forms of monogenic diabetes are autosomal dominant, which means a child can inherit the condition from one parent. However, some children with monogenic diabetes have new (de novo) mutations that do not come from either parent.
Outward signs of monogenic diabetes are similar to those for the more common forms of diabetes, including frequent urination, excessive thirst and dehydration.
Diagnosis is made after observing the child’s symptoms and taking a history, including a family history. Small size, for example, is characteristic of NDM, and a genetic cause will be suspected if symptoms of diabetes appear in infancy. If symptoms suggest diabetes, blood tests are done to measure:
- Glucose levels
- How much insulin the body is making
- The presence or absence of autoantibodies
High glucose levels and insufficient insulin production are indicators of diabetes, and the absence of autoantibodies can suggest monogenic diabetes. (Autoantibodies are generally present in type 1 diabetes.)
If the symptoms, history and tests suggest monogenic diabetes, a genetic test is done, initially for the child and possibly for immediate family members, to confirm the diagnosis and identify the specific gene mutation.
Children with monogenic diabetes are often misdiagnosed with type 1 diabetes and treated with injections of insulin. While some forms of monogenic diabetes require insulin to control blood sugars, patients with other forms of monogenic diabetes do better with different treatments, including oral medications. Some are able to manage the symptoms with diet and exercise alone, and no medication.
Children with some forms of monogenic diabetes may also require treatment for other health problems, such as digestive enzyme deficiencies, kidney cysts, low magnesium levels or autism.
Mitochondrial disorders impair the function of mitochondria, the tiny compartments in every cell of the body that produce the energy needed by cells. Depending on which cells have fewer or lower-functioning mitochondria, different symptoms may occur. Organs and body parts that require more energy, such as the heart, muscles and brain, are often affected.
Mitochondrial disease is the name for a large number of mitochondrial disorders, with different genetic causes and presentations. Friedreich’s ataxia is one form of inherited mitochondrial disease that impairs mitochondrial energy production that particularly involves dysfunction of the cerebellum, the part of the brain that helps plan and coordinate movements.
The body’s production of insulin depends on mitochondrial activity. If a mitochondrial disorder affects the cells in the pancreas that produce insulin, diabetes can be a feature of the patient’s mitochondrial disorder. Mitochondrial disorders may also cause insulin resistance in multiple body tissues, which increases the amount of insulin needed to control the absorption of glucose from the blood into fat, liver and muscle cells.
Diabetes can sometimes be the presenting symptom that leads to the genetic diagnosis of mitochondrial disorder. In other cases, diabetes may develop after the genetic diagnosis has already been made.
Treatment of a child’s diabetes that occurs due to an inherited mitochondrial disorder must be done in close collaboration with the different specialists who are treating the child. Some of the approaches to treat diabetes may be particularly helpful (or harmful) for other aspects of the condition, and medications or therapies that are used to treat other aspects of a child’s mitochondrial disease may affect the course or management of their diabetes.
Understanding the dynamics of diabetes when it occurs in the context of mitochondrial disorder is also critical to devise effective treatment. For example, some children with mitochondrial disease may develop high blood sugar levels and require insulin when they are ill or stressed, but not at other times. Some of these same children are also at risk for developing low blood sugar levels. It is important to individualize the approach to diabetes in the context of each child’s genetic diagnosis.
Lipodystrophy is a rare disorder that affects how the body stores and uses fat. Instead of being stored as body fat, under the skin, fat builds up in places it shouldn’t, like the blood and internal organs. This can cause diabetes, fatty liver disease, and other health problems.
Lipodystrophy can be inherited from one or both parents, or it can occur with no known genetic cause.
Diagnosis is made after taking a history of the symptoms, including a detailed family history, and conducting a complete physical exam. If symptoms suggest lipodystrophy, additional tests may be done, including:
- Blood tests to measure levels of leptin (a hormone produced by fat tissue), glucose and triglyceride (fat) in the blood
- An ultrasound of the liver to check for fat buildup
- An MRI to show where fat has accumulated or is missing
- Genetic testing
Treatment varies with the type of lipodystrophy diagnosed. It may include:
- A low-carbohydrate/low-fat diet
- Physical activity to reduce blood sugar and fat
- Medication to treat diabetes and manage the levels of fat in the blood
As with mitochondrial diabetes, treatment for diabetes with lipodystrophy must be done in close collaboration with the different specialists who are treating the child.
Physicians in CHOP’s Monogenic and Atypical Diabetes Program have expertise in the diagnosis and treatment of these rarer forms of diabetes. We perform evaluations to properly identify patients with monogenic and atypical diabetes, and to diagnose the specific forms of the conditions. We then establish individualized treatment programs for these patients, and work closely with families and the other specialists to manage those treatment plans.
The Monogenic and Atypical Diabetes Program works closely with CHOP’s Mitochondrial Medicine, a Frontier Program, and Friedreich’s Ataxia Program.