A Diabetic Subject With MELAS and Antiphospholipid Syndrome

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome has been reported to coexist with autoimmune type 1 diabetes (1) and Graves’ disease (2). We described, for the first time, a diabetic patient with MELAS syndrome, autoimmune hemolytic anemia, and antiphospholipid syndrome.

During routine health examination, a 38-year-old man was diagnosed with diabetes. There was no family history of diabetes. On 22 January 2001, he was admitted due to right hemiparesis, slurred speech, and headache. Magnetic resonance imaging of the brain revealed increased signal intensity on diffusion scan with decreased apparent diffusion coefficient confined to left middle cerebral arterial territory, which was compatible with acute ischemic infarct. For his young stroke, we checked carotid duplex, cardiac sonography, anti-nuclear antibodies, rheumatic factors, protein C, and protein S, which were all negative. The level of antiphospholipid antibodies was 14.7 phospholipid units/ml (normal <5, positive >15) and that of anticardiolipin antibodies was 17.5 phospholipid units/ml (normal <16, positive >21). He was then discharged in stable condition. Serum markers were repeated on 16 July 2001 and showed positivity for antiphospholipid antibodies (19.5 phospholipid units/ml) and anticardiolipin antibodies (22.4 phospholipid units/ml). Antiphospholipid syndrome was favored due to a history of vascular thrombosis and the presence of circulating antibodies. However, gradual loss of cognition and muscle power developed progressively. Bilateral hearing impairment was found, and the patient was once again admitted for hyperglycemia with metabolic acidosis on 11 July 2001. Serum lactic acid was high (6.95 mmol/l). The presence of lactic acidosis, bilateral hearing loss, progressive muscle weakness, young stroke, and diabetes prompted us to examine him for mitochondrial disease. MELAS syndrome was then diagnosed with a demonstration of an A-to-G point mutation at position 3243 of mitochondrial DNA. No such a mutation was found in his mother or siblings, indicating that a de novo mutation occurred in this subject. Besides, autoimmune hemolytic anemia was also found during admission (hemoglobin 9.0 g/dl, mean corpuscular volume 91.6 fl, reticulocyte count 10.81%, haptoglobin <5.83 mg/dl, direct Coombs test 2+, antinuclear antibodies [−] 1:160, and rheumatoid factor <20 IU/ml). His condition deteriorated progressively, and he died 5 months later of pneumonia.

It is difficult to distinguish patients with antiphospholipid syndrome from MELAS syndrome based on brain image studies. Patients with antiphospholipid syndrome may suffer from oxidant-mediated injury (3). Since the mitochondrial genome lacks a DNA repairing system and protecting proteins, it is susceptible to oxidative stress. Thus, the presence of antiphospholipid syndrome might be one of the causes of de novo mutation or may accelerate accumulation of mutated DNA, which may result in a rapidly deteriorating course such as that seen in this patient. We therefore suggest that patients with MELAS syndrome be examined for the presence of antiphospholipid syndrome, especially those presenting with vascular thrombosis.