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by Michael D. Brown, Ph.D.
Geneticists believe that there may be as many as 100 mutations responsible for hearing loss or deafness in humans. Around 30 have been identified to date, including a rare one that causes both sensorineural hearing loss and diabetes. People who have the disorder that results from this mutation, Maternally Inherited Diabetes and Deafness (MIDD), comprise an estimated 0.5 to 2 percent of the nearly 200 million diabetics worldwide.
Most people with MIDD start to lose their hearing before developing diabetes, which can occur early in life or by the middle-age years. This form of diabetes is difficult to categorize as type 1 or 2 because affected individuals may initially be able to control the disease without relying on insulin treatment but often progress to being insulin dependent. In terms of the effects of the disorder on hearing, MIDD is perhaps a bit misleading since the degree of hearing loss is variable in patients.
Because it is a genetic disease, it is important to understand various features of MIDD and their implications for future generations. First and foremost, the mutation that causes MIDD is passed only by a mother to her offspring and subsequently from her daughters to their children. Men can inherit the disorder but they cannot transmit it to their children. The explanation for this pattern lies in the curiously complex root of the disease.
MIDD is caused by malfunctions that occur in a part of our cells called the mitochondria - the "powerplants" of the cell that provide energy for normal cellular function. These cellular components have their own DNA, mitochondrial DNA (mtDNA), and their own set of genes with the potential for mutations. When mutation occurs, it often leads to defective mitochondria that in turn cause dysfunction and disease. MIDD usually results from a particular mutation that has been pinpointed to mtDNA position 3243.
Interestingly, the familiar principles of genetic inheritance that dictate that both mother and father contribute equally to a child's makeup do not apply to mtDNA. In fact, sperm contain very few mitochondria and essentially all are destroyed upon fertilization of an egg, the reason that MIDD can only be passed from mothers to offspring. Transmission may be sporadic (i.e., the disease may skip a generation or two) or it may occur frequently.
Also, because each cell can have hundreds of mitochondria each, people with the 3243 mutation typically have a mixture of mutated and normal mtDNA in their cells, a condition called heteroplasmy. As a result, although most will develop MIDD, some may have different clinical symptoms, including those that arise from a severe neurological disease.
Heteroplasmy also explains how a person can be a carrier of MIDD but may remain unaffected by the disease - individuals with low levels of mutation may never develop symptoms. Finally, genetic testing for the 3243 mutation is widely available and can confirm a diagnosis of MIDD. It can also indicate that an individual is a heteroplasmic carrier and is therefore at risk for MIDD or if a woman, of passing the mutation to her children. It is advisable for individuals with a family history of hearing loss and diabetes and/or neurological disease along maternal lines to be tested for the mutation. The primary care physician should also be aware of the family medical history and recommend a plan for monitoring diabetes status and hearing ability.
There are still many questions concerning the underlying molecular mechanism of MIDD. Indeed, we do not yet know whether a diabetes prevention lifestyle (i.e., regular physical activity and a healthy diet) will delay or stop the onset or progression of the disease. Growing knowledge of how the various types of diabetes and hearing loss interact and the rapid pace of discovery in mitochondrial research may facilitate efforts towards the development of an effective treatment for MIDD.
Michael D. Brown, Ph.D., is associate professor of genetics and pediatrics at the Mercer University School of Medicine in Macon, Georgia. |
