Transient neonatal diabetes mellitus

Permanent neonatal diabetes mellitus (PNDB) is a type of diabetes that appears within the first 6 months of life and persists throughout life. Affected individuals have slow growth before birth followed by hyperglycemia, dehydration and failure to thrive in infancy. Some individuals also have neurological problems including developmental delay and epilepsy; when these problems are present with PNDB, it is called DEND syndrome. A few individuals with PNDB also have an underdeveloped pancreas and may have digestive problems. PNDB is caused by mutations in any one of several genes (some of which have not yet been identified) including the KCNJ11, ABCC8, and INS genes. It may be inherited in an autosomal recessive or autosomal dominant manner.^[1] Treatment includes rehydration, insulin therapy and/or long-term therapy with oral sulfonylureas (in some cases).^[2]

Transient neonatal diabetes mellitus (TNDB) is a type of diabetes that appears within the first few weeks of life but is transient; affected infants go into remission within a few months, with possible relapse to permanent diabetes in adolescence or adulthood.^[3] Affected individuals have slow growth before birth followed by hyperglycemia, dehydration and failure to thrive in infancy.^[1] Approximately 70% of cases are caused by the overactivity of certain genes in a region of the long (q) arm of chromosome 6 called 6q24.^[4][5] These cases are referred to as 6q24-related TNDB; most (but not all) of these cases are not inherited.^[5] Other genetic causes include mutations in the KCNJ11 and ABCC8 genes, which usually cause permanent neonatal diabetes.^[4] Treatment may include rehydration and intravenous insulin at the time of diagnosis, followed by subcutaneous insulin.^[4]

The outlook for individuals with neonatal diabetes mellitus (NDM) varies among affected individuals. Among affected infants, some have permanent diabetes, others have remission of their diabetes and later recurrence, and still others have apparently permanent remission. Since diabetes may recur in childhood or adulthood, it is often not possible to consider any remission permanent.^[6] It has been estimated that neonatal diabetes mellitus will be transient in about 50 percent (half) of cases.^[6]

In the neonatal period, the prognosis is generally related to the severity of the disease, the degree of dehydration and acidosis, as well how quickly the disease is diagnosed and treated. The presence of associated abnormalities may also affect an individual's prognosis. The long-term outlook often depends on the individual's metabolic control (as in all forms of diabetes mellitus), which affects the presence and severity of diabetes-related complications.^[7] Furthermore, the prognosis may be better determined with knowledge of the underlying genetic cause of the disease.^[8] With proper management, the overall prognosis for general health and normal intellectual development is usually good.^[6]

Individuals seeking prognosis information for themselves or family members should speak with their health care professional.

When neonatal diabetes mellitus (NDM) is first diagnosed, it is difficult to determine if it is likely to be transient (TNDM) or permanent (PNDM).^[2] The two typically cannot be distinguished based on signs and symptoms alone.^[3] Genetic testing can help determine which form of NDM is present.

The two most common causes of neonatal diabetes are 6q24-related TNDM and mutations in the KCNJ11 gene. It has been suggested that for infants presenting in the first two weeks of life, it is reasonable to test for 6q24-related TNDM first, followed by testing for KCNJ11, INS and/or ABCC8 mutations.^[2][4] For infants presenting from the fourth week of life onwards, it may be more appropriate to test for KCNJ11 and INS mutations first, followed by testing for 6q24-related TNDM.^[4]

Testing for other genetic causes, or testing for the above-mentioned causes in a different order, may be appropriate for some individuals depending on the presence of additional features, family history, or consanguineous parents.^[4]

Individuals interested in learning more about genetic testing for neonatal diabetes mellitus should speak with their health care provider or a genetics professional.

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.