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Genetics Home Reference: your guide to understanding genetic conditions
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Maternally inherited diabetes and deafness

(often shortened to MIDD)
Reviewed October 2012

What is MIDD?

Maternally inherited diabetes and deafness (MIDD) is a form of diabetes that is often accompanied by hearing loss, especially of high tones. The diabetes in MIDD is characterized by high blood sugar levels (hyperglycemia) resulting from a shortage of the hormone insulin, which regulates the amount of sugar in the blood. In MIDD, the diabetes and hearing loss usually develop in mid-adulthood, although the age that they occur varies from childhood to late adulthood. Typically, hearing loss occurs before diabetes.

Some people with MIDD develop an eye disorder called macular retinal dystrophy, which is characterized by colored patches in the light-sensitive tissue that lines the back of the eye (the retina). This disorder does not usually cause vision problems in people with MIDD. Individuals with MIDD also may experience muscle cramps or weakness, particularly during exercise; heart problems; kidney disease; and constipation. Individuals with MIDD are often shorter than their peers.

How common is MIDD?

About 1 percent of people with diabetes have MIDD. The condition is most common in the Japanese population and has been found in populations worldwide.

What are the genetic changes related to MIDD?

Mutations in the MT-TL1, MT-TK, or MT-TE gene cause MIDD. These genes are found in mitochondrial DNA, which is part of cellular structures called mitochondria. Although most DNA is packaged in chromosomes within the cell nucleus, mitochondria also have a small amount of their own DNA (known as mitochondrial DNA or mtDNA).

The MT-TL1, MT-TK, and MT-TE genes provide instructions for making molecules called transfer RNAs (tRNAs), which are chemical cousins of DNA. These molecules help assemble protein building blocks (amino acids) into functioning proteins. The MT-TL1 gene provides instructions for making a specific form of tRNA that is designated as tRNALeu(UUR). During protein assembly, this molecule attaches to the amino acid leucine (Leu) and inserts it into the appropriate locations in the growing protein. Similarly, the protein produced from the MT-TK gene, called tRNALys, attaches to the amino acid lysine (Lys) and inserts it into proteins being assembled. Also, the protein produced from the MT-TE gene, called tRNAGlu, attaches to the amino acid glutamic acid (Glu) and adds it to growing proteins.

These tRNA molecules are present only in mitochondria, and they help assemble proteins that are involved in producing energy for cells. In certain cells in the pancreas called beta cells, mitochondria also play a role in controlling the amount of sugar (glucose) in the bloodstream. In response to high glucose levels, mitochondria help trigger the release of insulin, which stimulates cells to take up glucose from the blood.

Mutations in the MT-TL1, MT-TK, or MT-TE gene reduce the ability of tRNA to add amino acids to growing proteins, which slows protein production in mitochondria and impairs their functioning. Researchers believe that the disruption of mitochondrial function lessens the ability of mitochondria to help trigger insulin release. In people with this condition, diabetes results when the beta cells do not produce enough insulin to regulate blood sugar effectively. Researchers have not determined how the mutations lead to hearing loss or the other features of MIDD.

Related Gene(s)

Changes in these genes are associated with maternally inherited diabetes and deafness.

  • MT-TE
  • MT-TK
  • MT-TL1

How do people inherit MIDD?

MIDD is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mitochondrial DNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, only females pass mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children.

Most of the body's cells contain thousands of mitochondria, each with one or more copies of mitochondrial DNA. These cells can have a mix of mitochondria containing mutated and unmutated DNA (heteroplasmy). The severity of MIDD is thought to be associated with the percentage of mitochondria with the mitochondrial DNA mutation.

Where can I find information about diagnosis or management of MIDD?

These resources address the diagnosis or management of MIDD and may include treatment providers.

  • Genetic Testing Registry: Diabetes-deafness syndrome maternally transmitted (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0342289)

You might also find information on the diagnosis or management of MIDD in Educational resources (http://www.ghr.nlm.nih.gov/condition/maternally-inherited-diabetes-and-deafness/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/maternally-inherited-diabetes-and-deafness/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about MIDD?

You may find the following resources about MIDD helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for MIDD?

  • Ballinger-Wallace syndrome
  • diabetes mellitus, type II, with deafness
  • maternally transmitted diabetes-deafness syndrome
  • mitochondrial inherited diabetes and deafness
  • NIDDM with deafness
  • noninsulin-dependent diabetes mellitus with deafness

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about MIDD?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding MIDD?

acids ; amino acid ; cell ; cell nucleus ; constipation ; diabetes ; diabetes mellitus ; DNA ; egg ; embryo ; gene ; Glu ; glucose ; glutamic acid ; heteroplasmy ; high blood sugar ; hormone ; hyperglycemia ; inheritance ; inherited ; insulin ; kidney ; Leu ; leucine ; Lys ; lysine ; maternal ; maternal inheritance ; mitochondria ; molecule ; mutation ; nucleus ; pancreas ; pattern of inheritance ; population ; protein ; retina ; sperm ; syndrome ; tissue ; tRNA

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Kameoka K, Isotani H, Tanaka K, Kitaoka H, Ohsawa N. Impaired insulin secretion in Japanese diabetic subjects with an A-to-G mutation at nucleotide 8296 of the mitochondrial DNA in tRNA(Lys). Diabetes Care. 1998 Nov;21(11):2034-5. (http://www.ncbi.nlm.nih.gov/pubmed/9802769?dopt=Abstract)
  • Maassen JA, Jahangir Tafrechi RS, Janssen GM, Raap AK, Lemkes HH, 't Hart LM. New insights in the molecular pathogenesis of the maternally inherited diabetes and deafness syndrome. Endocrinol Metab Clin North Am. 2006 Jun;35(2):385-96, x-xi. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16632100?dopt=Abstract)
  • Murphy R, Turnbull DM, Walker M, Hattersley AT. Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation. Diabet Med. 2008 Apr;25(4):383-99. doi: 10.1111/j.1464-5491.2008.02359.x. Epub 2008 Feb 18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18294221?dopt=Abstract)
  • Supale S, Li N, Brun T, Maechler P. Mitochondrial dysfunction in pancreatic β cells. Trends Endocrinol Metab. 2012 Sep;23(9):477-87. doi: 10.1016/j.tem.2012.06.002. Epub 2012 Jul 4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22766318?dopt=Abstract)
  • van den Ouweland JM, Lemkes HH, Ruitenbeek W, Sandkuijl LA, de Vijlder MF, Struyvenberg PA, van de Kamp JJ, Maassen JA. Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat Genet. 1992 Aug;1(5):368-71. (http://www.ncbi.nlm.nih.gov/pubmed/1284550?dopt=Abstract)
  • Vialettes BH, Paquis-Flucklinger V, Pelissier JF, Bendahan D, Narbonne H, Silvestre-Aillaud P, Montfort MF, Righini-Chossegros M, Pouget J, Cozzone PJ, Desnuelle C. Phenotypic expression of diabetes secondary to a T14709C mutation of mitochondrial DNA. Comparison with MIDD syndrome (A3243G mutation): a case report. Diabetes Care. 1997 Nov;20(11):1731-7. (http://www.ncbi.nlm.nih.gov/pubmed/9353617?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2012
Published: December 16, 2014