A 26-year-old woman presented with vomiting and cortical blindness. CT scan of the brain confirmed a right-sided parietal-occipital infarct, She subsequently developed seizures and neurological extension resulting in global dysphasia. Serum and CSF lactate were elevated (4.4 and 4.3 mmol/l respectively, NR<1.8). MELAS syndrome was confirmed by mitochondrial DNA analysis, which revealed an A3243G mutation in muscle and serum (85% muscle, 63% urinary epithelial cells and 33% blood heteroplasmy). Muscle biopsy revealed characteristic ragged-red fibres. Examination revealed a BMI of 18.9 and was suggestive of thyrotoxicosis, which was confirmed (fT4 27.2 pmol/l, fT3 7.3 pmol/l, TSH <0.05 mU/l, TSH receptor antibody positive). Euthyroidism was restored and maintained with carbimazole.
Her previous history revealed insulin-dependent diabetes aged 22 and, two months prior to the current illness, a stroke like episode resulting in left-sided neglect. At that time a diagnosis of subclinical hyperthyroidism was made (TSH<0.05 mU/l, fT4 15.1 pmol/l and fT3 3.7 pmol/l).
MELAS syndrome most commonly results from an A3243G transition in the mitochondrial gene encoding tRNA for leucine (MTTL1). It is associated with diabetes, cardiomyopathy and progressive renal failure, but the A3243G transition also causes the distinct syndrome of diabetes with sensori-neural deafness. The mutation is thought to sensitise affected tissues to oxidative stresses, such as exposure to sodium valproate which can precipitate seizures. Progressively impaired oxidative phosphorylation is manifest by reduced pyruvate dehydrogenase and respiratory chain complex I and IV activities in tissues with high heteroplasmy. Clinical severity varies in proportion to the quantity of mutated mitochondrial DNA in different tissues. MELAS syndrome and thyrotoxicosis has been described once before: a woman with the A3243G mutation suffered lactic acidosis and recurrent seizures. We propose the catastrophic event in this case was precipitated by the metabolic stress of uncontrolled thyrotoxicosis.
06 - 07 Nov 2006
Society for Endocrinology