Endocrine Abstracts

In 1981 a 33 yr old woman was diagnosed with Graves thyrotoxicosis and type 2 diabetes mellitus. At diagnosis her BMI was 19 kg/m² and she was initially treated with carbimazole and glibenclamide. She had a past medical history of idiopathic lymphoedema, asthma and bronchopulmonary aspergillosis and was regularly reviewed by an ophthalmologist for hyperpigmented maculae.

In 1991 she required insulin to control her diabetes and developed progressive bilateral neurosensory hearing loss. She was later diagnosed with restless leg syndrome and then progressive ataxia. A more detailed enquiry revealed a family history of deafness, diabetes mellitus and visual problems in her mother and daughter. A diagnosis of maternally inherited diabetes and deafness (MIDD) was suspected. A muscle biopsy confirmed the presence of ragged-red fibres and an A3243G mutation was detected on genetic testing.

MIDD is a new sub-type of diabetes and usually results from an A to G substitution at position 3243 of the mitochondrial tRNA (leu(UUR)) gene. The mean age of onset is 35yrs and patients usually have a normal/low BMI and normal insulin sensitivity. The prevalence of MIDD is unclear. Clinical features include neurosensory hearing loss (90%), myopathy (43%), cardiomyopathy (15%), renal disease (28%), macular dystrophy (86%) and specific retinal lesions. Macular/retinal dystrophy has a classical appearance and distribution and is a clue to the diagnosis. Patients do not typically develop classic diabetic retinopathy. Hypoparathyroidism, ACTH deficiency, ovarian or hypothalamic dysfunction, seizures, dementia, ataxia and migraine may also feature. There is no single diagnostic test though lactate to pyruvate ratios may be helpful in diagnosis and monitoring. Ragged-red fibres on muscle biopsy are characteristic of mitochondrial disorders. There is no cure for MIDD and no specific treatments are available though coenzyme Q10 may improve the insulin secretory response, prevent progressive hearing loss and reduce exercise induced lactate levels.