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MIDD (maternally inherited diabetes and deafness)
MIDD is a genetic condition that affects the body's energy production, primarily leading to a type of diabetes and progressive hearing loss. It is passed down through the maternal line, meaning it is inherited from the mother.
Overview
Maternally Inherited Diabetes and Deafness (MIDD) is a rare genetic condition defined by two main features: diabetes and sensorineural hearing loss [PMID:10729221]. Individuals with MIDD typically develop diabetes in early to mid-adulthood, often presenting before the age of 40. The hearing impairment is usually progressive and can vary in severity. MIDD is part of a group of disorders caused by changes in the DNA of mitochondria, which are the 'powerhouses' of our cells.
Symptoms & clinical features
The primary symptoms of MIDD are diabetes and hearing loss. The diabetes in MIDD is often diagnosed in individuals under 40 years old and may initially be mistaken for Type 1 or Type 2 diabetes. However, it often has unique features, such as not being strongly associated with obesity or autoimmune markers typically seen in other diabetes types [PMID:10729221]. The hearing loss is sensorineural, meaning it results from damage to the inner ear or the nerve pathways from the inner ear to the brain. This loss can vary significantly between individuals, even within the same family, and usually worsens over time. Some individuals may also experience other symptoms, such as problems with the kidneys, eyes, or nervous system, though these are less common.
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Affected organs
MIDD primarily affects the pancreas, leading to diabetes, and the inner ear, causing hearing loss. The pancreas produces insulin, a hormone vital for regulating blood sugar. In MIDD, the mitochondrial changes can impair the ability of pancreatic cells to produce or release enough insulin. The inner ear's delicate structures rely heavily on mitochondrial energy for proper function, so mitochondrial dysfunction can lead to progressive hearing impairment. In some cases, other organs such as the kidneys, eyes (e.g., pigmentary retinopathy), and less commonly, the heart or nervous system, can also be affected.
Risks & severity
The severity of MIDD can vary widely among affected individuals, even within the same family. The diabetes component typically develops in early to mid-adulthood, often before 40 years of age, but the exact age of onset can differ. The hearing loss is usually progressive and can range from mild to profound. The progression of both diabetes and hearing loss is variable, making it difficult to predict individual outcomes. While MIDD is a chronic condition, with appropriate management, individuals can often maintain a good quality of life. The exact prevalence of MIDD is not well established, but it is considered a rare condition.
Genetic causes
MIDD is caused by specific changes in the mitochondrial DNA (mtDNA). Unlike most of our DNA, which is found in the cell's nucleus, mitochondrial DNA resides in the mitochondria themselves. Mitochondria are responsible for generating most of the energy needed for cellular function. Pathogenic variants in mtDNA, particularly the m.3243A>G variant in the MT-TL1 gene (which codes for a transfer RNA), are the most common cause of MIDD [PMID:24637777]. These changes disrupt the normal functioning of mitochondria, impairing energy production and leading to the symptoms seen in MIDD. The presence of these altered mitochondria alongside normal mitochondria, a state called heteroplasmy, can influence the severity of the condition.
Inheritance pattern
MIDD follows a mitochondrial inheritance pattern. This means the condition is inherited exclusively from the mother. All children of an affected mother will inherit her mitochondrial DNA, and therefore the genetic change, regardless of their sex. However, not all individuals who inherit the genetic change will develop symptoms, or they may develop them to varying degrees, due to the concept of heteroplasmy (the proportion of altered mitochondrial DNA). Fathers cannot pass on mitochondrial conditions to their children [PMID:24637777].
Diagnosis & testing
Diagnosing MIDD often involves a combination of clinical assessment and genetic testing. If an individual presents with diabetes, particularly at a young age, along with hearing loss, MIDD may be suspected. A detailed family history is crucial, looking for a maternal pattern of inheritance for similar symptoms. Genetic testing for mitochondrial DNA changes, especially for the common m.3243A>G variant, confirms the diagnosis [PMID:24637777]. This testing can be arranged through the NHS Genomic Medicine Service (GMS) after a referral from a specialist, such as an endocrinologist or clinical geneticist. Relevant NHS Genomic Medicine Service R-codes would be applied for such testing, which is typically requested by a clinical genetics service or specialist. A genetic counsellor can help explain the testing process and implications.
Management & lifestyle
Management of MIDD focuses on addressing the specific symptoms experienced by the individual. Diabetes is managed similar to other forms of diabetes, often requiring insulin or oral medications, and careful monitoring of blood sugar levels. A healthy lifestyle, including a balanced diet and regular exercise, is generally advised. Hearing loss can be managed with hearing aids, and in some cases, cochlear implants may be considered. Regular follow-ups with an endocrinologist for diabetes and an audiologist for hearing are essential. Patients may also benefit from a multidisciplinary team approach, including dietitians, ophthalmologists, and nephrologists, depending on other symptoms. It is important for individuals with MIDD to avoid certain medications, like aminoglycoside antibiotics, which can worsen hearing loss.
UK care pathway
In the UK, individuals suspected of having MIDD would typically be referred to a clinical genetics service, often following initial assessments by an endocrinologist or audiologist. The NHS Genomic Medicine Service (GMS) provides comprehensive genetic testing, guided by national R-codes, to confirm the diagnosis. Clinical geneticists and genetic counsellors play a crucial role in coordinating care, explaining genetic test results, and discussing implications for the individual and their family. They can also advise on appropriate surveillance and management strategies, linking patients to specialist care.
Frequently asked questions
How does MIDD differ from Type 1 or Type 2 diabetes?
MIDD diabetes often presents at a younger age than Type 2, is typically not associated with obesity, and can lack the autoimmune markers seen in Type 1 diabetes. The key distinguishing factor is the presence of maternally inherited hearing loss and specific mitochondrial DNA changes.
Can MIDD affect my children?
If you are a woman with MIDD, all of your children will inherit the mitochondrial genetic change. However, the severity of symptoms can vary widely, and some may not develop symptoms at all, or only very mild ones. Men with MIDD cannot pass the condition to their children.
Is there a cure for MIDD?
Currently, there is no cure for MIDD. However, symptoms can be effectively managed. Treatments focus on controlling diabetes through medication and lifestyle changes, and addressing hearing loss with aids or implants to improve quality of life.
What kind of doctors will I need to see for MIDD?
You will likely see a team of specialists, including an endocrinologist for diabetes management, an audiologist for hearing care, and a clinical geneticist or genetic counsellor for genetic aspects. Other specialists may be involved depending on any additional symptoms.
Are there any medications I should avoid if I have MIDD?
Yes, individuals with MIDD are generally advised to avoid aminoglycoside antibiotics, as these medications can worsen hearing loss. Always inform your healthcare providers about your MIDD diagnosis before starting any new medications.
References
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- Aitman TJ, Todd JA. Molecular genetics of diabetes mellitus. Bailliere's clinical endocrinology and metabolism. 1995. PMID: 7575335
- Dabravolski SA, Orekhova VA, Baig MS. The Role of Mitochondrial Mutations and Chronic Inflammation in Diabetes. International journal of molecular sciences. 2021. PMID: 34201756
- de Laat P, Janssen MC, Alston CL. Three families with 'de novo' m.3243A > G mutation. BBA clinical. 2016. PMID: 27331024
- Maassen JA, 't Hart LM, Janssen GM. Mitochondrial diabetes and its lessons for common Type 2 diabetes. Biochemical Society transactions. 2006. PMID: 17052206
- Świerczyńska M, Danikiewicz-Zagała M, Sedlak L. Choroidal neovascularization associated with butterfly-shaped pattern dystrophy - a case report. Romanian journal of ophthalmology. 2023. PMID: 37522013
- Maresca A, Moresco M, Amore G. Biomarking MELAS with neurofilament light chain and circulating cell free mitochondrial DNA. Molecular genetics and metabolism. 2026. PMID: 41637969
- Mancuso M, Orsucci D, Angelini C. The m.3243A>G mitochondrial DNA mutation and related phenotypes. A matter of gender? Journal of neurology. 2014. PMID: 24375076