Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-onset Diabetes of the Young
What is neonatal diabetes mellitus (NDM)?
NDM is a monogenic form of diabetes that occurs in the first 6 months of life. It is a rare condition occurring in only one in 100,000 to 500,000 live births. Infants with NDM do not produce enough insulin, leading to an increase in blood glucose. NDM can be mistaken for the much more common type 1 diabetes, but type 1 diabetes usually occurs later than the first 6 months of life. In about half of those with NDM, the condition is lifelong and is called permanent neonatal diabetes mellitus (PNDM). In the rest of those with NDM, the condition is transient and disappears during infancy but can reappear later in life; this type of NDM is called transient neonatal diabetes mellitus (TNDM). Specific genes that can cause NDM have been identified. More information about each type of NDM is provided in the appendix.
Symptoms of NDM include thirst, frequent urination, and dehydration. NDM can be diagnosed by finding elevated levels of glucose in blood or urine. In severe cases, the deficiency of insulin may cause the body to produce an excess of acid, resulting in a potentially life-threatening condition called ketoacidosis. Most fetuses with NDM do not grow well in the womb and newborns are much smaller than those of the same gestational age, a condition called intrauterine growth restriction. After birth, some infants fail to gain weight and grow as rapidly as other infants of the same age and sex. Appropriate therapy improves and may normalize growth and development.
What is maturity-onset diabetes of the young (MODY)?
MODY is a monogenic form of diabetes that usually first occurs during adolescence or early adulthood. However, MODY sometimes remains undiagnosed until later in life. A number of different gene mutations have been shown to cause MODY, all of which limit the ability of the pancreas to produce insulin. This process leads to the high blood glucose levels characteristic of diabetes and, in time, may damage body tissues, particularly the eyes, kidneys, nerves, and blood vessels. MODY accounts for about 1 to 5 percent of all cases of diabetes in the United States. Family members of people with MODY are at greatly increased risk for the condition.
People with MODY may have only mild or no symptoms of diabetes and their hyperglycemia may only be discovered during routine blood tests. MODY may be confused with type 1 or type 2 diabetes. People with MODY are generally not overweight and do not have other risk factors for type 2 diabetes, such as high blood pressure or abnormal blood fat levels. While both type 2 diabetes and MODY can run in families, people with MODY typically have a family history of diabetes in multiple successive generations, meaning that MODY is present in a grandparent, a parent, and a child. Unlike people with type 1 diabetes who always require insulin, people with MODY can often be treated with oral diabetes medications. Treatment varies depending on the genetic mutation that has caused the MODY. More information about each type of MODY is provided in the appendix.
What do I need to know about genetic testing and counseling?
Testing for monogenic diabetes involves providing a blood sample from which DNA is isolated. The DNA is analyzed for changes in the genes that cause monogenic diabetes. Abnormal results can determine the gene responsible for diabetes in a particular individual or show whether someone is likely to develop a monogenic form of diabetes in the future. Genetic testing can also be helpful in selecting the most appropriate treatment for individuals with monogenic diabetes. Prenatal testing can diagnose these conditions in unborn children.
Most forms of monogenic diabetes are caused by dominant mutations, meaning that the condition can be passed on to children when only one parent is affected. In contrast, if the mutation is a recessive mutation, a disease gene must be inherited from both parents for diabetes to occur. For recessive forms of monogenic diabetes, testing can indicate whether parents or siblings without disease are carriers for recessive genetic conditions that could be inherited by their children.
If you suspect that you or a member of your family may have a monogenic form of diabetes, you should seek help from health care professionals-physicians and genetic counselors-who have specialized knowledge and experience in this area. They can determine whether genetic testing is appropriate, select the genetic tests that should be performed, and provide information about the basic principles of genetics, genetic testing options, and confidentiality issues. They also can review the test results with the patient or parent after testing, make recommendations about how to proceed, and discuss testing options for other family members.
Hope through Research
Researchers are studying the genetic causes of and metabolic processes related to diabetes. Discoveries about monogenic forms of diabetes may contribute to the search for the causes of and treatments for type 1 and type 2 diabetes. For information about clinical trials related to diabetes and genetics, see www.ClinicalTrials.gov.
Points to Remember
For More Information
Information About Genetic Testing, Evaluation, and Counseling, Funded by the National Institutes of Health (NIH)
The GeneTests website provides information about medical genetics, an international directory of genetic testing laboratories, and an international directory of genetics clinics providing genetic evaluation and genetic counseling.
Information About Genetics
National Human Genome Research Institute
The Genetics Home Reference website provides consumer-friendly information about genetic conditions. A service of the National Library of Medicine (NLM), NIH.
The Online Mendelian Inheritance in Man database is a catalog of human genes and genetic disorders with references and related links. A service of the National Center for Biotechnology Information, NLM, NIH.
Entrez Gene is a searchable database of genes with extensive information and related links. A service of the National Center for Biotechnology Information, NLM, NIH.
The Diabetes Research department and the Centre for Molecular Genetics at the Peninsula Medical School and Royal Devon and Exeter Hospital, Exeter, United Kingdom provides information for patients and health care professionals about genetic forms of diabetes.
The International Society for Pediatric and Adolescent Diabetes is an international society for health care professionals and others interested in childhood diabetes. They publish consensus guidelines; see the list of selected references.
Information About Diabetes
For more information about diabetes, see Diabetes Overview, which is available from the National Diabetes Information Clearinghouse, or contactNational Diabetes Information Clearinghouse
1 Information Way
Bethesda, MD 20892-3560
American Diabetes Association
Appendix and Selected References
Appendix: Characteristics of Monogenic Forms of Diabetes
*Gene or Syndrome: the name of the gene with the mutation or the syndrome-a grouping of conditions that occur together and indicate a specific disease-caused by the mutated gene
**Type of Inheritance or Mutation:
***Transient or Permanent: whether the form of diabetes goes away after some time, called transient, or is permanent
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Colombo C, Delvecchio M, Zecchino C, Falenza MF, Cavallo L, Barbetti F. Transient neonatal diabetes mellitus is associated with a recurrent (R201H) KCNJ11 (Kir6.2) mutation. Diabetologia. 2005;48:2439-2441.
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National Diabetes Information Clearinghouse
The National Diabetes Information Clearinghouse (NDIC) is a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health of the U.S. Department of Health and Human Services. Established in 1978, the Clearinghouse provides information about diabetes to people with diabetes and to their families, health care professionals, and the public. The NDIC answers inquiries, develops and distributes publications, and works closely with professional and patient organizations and Government agencies to coordinate resources about diabetes.
Publications produced by the Clearinghouse are carefully reviewed by both NIDDK scientists and outside experts. This publication was reviewed by Mark A. Sperling, M.D., Department of Pediatrics, Children's Hospital, University of Pittsburgh; Kenneth S. Polonsky, M.D., Department of Medicine, Washington University School of Medicine; and Concepcion R. Nierras, Ph.D., Juvenile Diabetes Research Foundation International.
This publication is not copyrighted. The Clearinghouse encourages users of this publication to duplicate and distribute as many copies as desired.
NIH Publication No. 07-6141