42 year old woman presented with ischaemic left leg pain. There had been a right above knee amputation two years previously when Buerger's disease was diagnosed. However, on review of the arteriogram there was proximal disease in the superficial femoral artery suggesting atherosclerotic disease, and typical arteriographic features of Buerger's disease were absent. She had been a smoker of 30 cigarettes per day since age 16 years. At presentation two years after the right above knee amputation, the posterior tibial and dorsalis pedis pulses were absent in the left foot but there were no ischaemic ulcers in the toes. The following investigations were normal or negative: fasting blood sugar, lipid profile, C reactive protein, antinuclear antibody, rheumatoid factor, complement, anticentromere antibody, anti-Scl-70, anticardiolipin antibody, and thrombophilia screen. An echocardiogram was also normal. Serum homocysteine was 117.9 µmol/l (5.5-13.6), serum methionine was 16 µmol/l (22-32), serum folic acid was 3.5 ng/ml (3.2-12.4), serum vitamin B12 was 225 pg/ml (158-1050), and serum vitamin B6 was 45 nmol/l (15-73). Genetic testing revealed the patient was homozygous (TT) for the C677T polymorphism of methylenetetrahydrofolate (MTHFR). QUESTIONS (1) Which conditions should be excluded before making a diagnosis of Buerger's disease? (2) What are the causes of a raised serum homocysteine? (3) What is the appropriate treatment for this patient?