Maternally Inherited Diabetes and Deafness (MIDD)

The main purpose of mitochondria is to generate energy within the cells by producing a substance called ATP, this allows the cell to perform their functions correctly. MIDD tends to affect the organs where cells are most active such as the pancreas and the cochlea (in the ear) and in some cases the retina (the back of the eye), the muscles, kidneys and brain.

MIDD affects up to 1% of all diabetes but often goes unrecognised and is misdiagnosed as either Type 1 or Type 2 diabetes. The average age at which diabetes develops is 37 years but it ranges from 11 years to 68 years of age and often needs insulin treatment. Those with MIDD are usually of normal body weight. MIDD leads to diabetes because it reduces the amount of insulin made by the beta cells in the pancreas.

The majority of people with MIDD can initially be treated with dietary changes or tablets. However insulin therapy is usually needed within 2 years of diagnosis reflecting the reduced insulin secretion.  Metformin, a commonly used treatment in diabetes is probably best avoided as Metformin is known to interfere with mitochondrial function and the risk of lactic acidosis may be increased although this has not been reported to date. 

The deafness is a result of the nerve to the ear being affected in both ears and develops in around 75% of people with MIDD who also have diabetes. The hearing loss typically develops in young adulthood (although may develop as children or later in life) and usually is present before the diabetes. The deafness is more common in men than women and men have more severe and rapidly progressive hearing loss. Half of those with hearing loss suffer a rapid decline in their hearing while the remainder have slowly progressive hearing loss over many years. Hearing loss is variable, but can require bilateral hearing aids; although it seldom leads to total deafness. Typically the impaired hearing relates to the inability to hear high frequencies. Early detection of deafness by periodic audiograms in children is important and prompt antibiotic treatment of any ear infections is also logical. Cochlear implants have been successful in cases of severe hearing loss in MIDD.

In keeping with other mitochondrial disorders, MIDD can, in some patients, result in other medical problems apart from diabetes and deafness.  As with the diabetes and deafness there is considerable variation in the extent to which these occur.  Even within one family individuals may have varying severity of clinical features with some having diabetes alone and others having many organs affected.

• Short stature is common and MIDD patients are frequently thin (body mass index less than 20).
• Heart problems: It is important to screen all MIDD patients in case they have heart involvement which can cause serious problems with the rhythm of the heart. This would include an ECG (and usually an echocardiogram) at age of 35 years, or earlier if there are any clinical features or history of problems in any family members. In high risk individuals this should be conducted annually. Statin medications should be used in those with cardiovascular risk factors.
• Myopathy (Muscle weakness): muscle problems of either weakness or cramps may be present in around 40% of cases of MIDD. This generally involves proximal muscles (shoulders, buttocks and thighs) which are used when climbing stairs and presents as exercise induced muscle cramps or weakness.
• Renal (kidney) disease: Protein is commonly found in the urine of MIDD patients, particularly in women. Renal disease sometimes presents before the diabetes or deafness. The most common renal problem is called focal segmental glomerular sclerosis and some patients develop end stage renal failure. Renal function should be monitored annually as part of the routine diabetes check up. Tablets called ACE inhibitors should be started early due to the high degree of renal complications and good blood pressure control is also important.
• Retina (back of the eyes): Problems can include macular dystrophy including pigmented lesions and thinning of the epithelium. Visual symptoms are rare but can include visual loss, night blindness, blind spots and dislike of bright lights. Most patients with this macular disease have had diabetes for more than 40 years and are aged over 40 years. Eye screening is important and should be carried out annually.
• Strokes: In young adults less than 45 years of age stroke may occur in around 1% of patients.
• Gastrointestinal disease: Gastrointestinal complaints may be quite common in MIDD, particularly constipation.

Genetic testing should be conducted to confirm the diagnosis, urine samples are preferred although blood, saliva or occasionally muscle biopsies may be taken.

Maternal adult relatives of patients with MIDD are at risk of developing diabetes, hearing loss, renal failure or heart problems so long term follow up of relatives is advisable.