When a child younger than six months of age is diagnosed with diabetes, there is likely an underlying monogenic cause, and the child is considered to have neonatal diabetes.
“Neonatal diabetes is rare and can be difficult to recognize, but the chance to make a difference is high when it is identified and treatment begins early,” said Siri A.W. Greeley, MD, PhD, Assistant Professor of Pediatrics and Medicine, Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, Kovler Diabetes Center, University of Chicago.
Dr. Greeley spoke on “Neonatal Diabetes: Identification, Initial Treatment and Transitioning the Parent” at Thursday’s Plenary Session.
He explained that a genetic cause can be found in 75 to 80 percent of children diagnosed with diabetes when they are younger than 6 months. Children diagnosed when they are 6 to 12 months old have only about a 5 percent chance of having a genetic cause.
“Genetic testing is key. Many genetic testing panels are not comprehensive, but if a limited genetic panel is negative, then further testing should be done in a lab offering complete testing, including for defects that are related to 6q24,” Dr. Greeley said.
There is no established best treatment for neonatal diabetes, but some forms such as 6q24-related transient neonatal diabetes may respond to oral medications instead of insulin, he noted.
Mutations of the KCNJ11 and the ABCC8 genes can also result in diabetes. When these proteins are disrupted, it affects the normal channel function. In these cases, diabetes is the result of failure of the channel to close appropriately in response to rising glucose. Patients with these mutations may respond to sulfonylurea therapy, which permits insulin secretion through closure of the channel, Dr. Greeley explained.
“Patients with diabetes that is caused by KCNJ11 and ABCC8 mutations are typically diagnosed before they are 6 months old, and are often misdiagnosed as having type 1 diabetes. And, in fact, they sometimes – although rarely – manifest later in life and may be confused with type 1 or type 2 diabetes,” he said.
KCNJ11 and ABCC8 mutations may include mild to severe neurodevelopmental delays, he explained, and these mutations may have implications for other family members. An affected patient’s children will have a 50 percent risk of inheriting the mutation and developing diabetes.
Insulin (INS) gene mutations are also typically diagnosed before a child is 6 months old and often may be misdiagnosed as type 1 diabetes. In rare cases, INS diabetes can manifest later in life and be confused with type 1 or type 2 diabetes. Lifelong insulin is required. And the patient’s children will be at a 50 percent risk of inheriting the mutation and developing diabetes, Dr. Greeley noted.
“Genetic testing in neonatal diabetes is not only important clinically and in terms of improving the patient’s quality of life, it is also cost effective in terms of lifelong treatment,” he said.
Dr. Greeley also noted that adult patients who describe themselves as having had a brief period of hyperglycemia as a baby should be questioned further about their medical history and should also undergo genetic testing.