Male,63 years(y) old, normal weight and height, cognitively adequate. From 30 to 53y he had: membranoproliferative glomerulonephritis, atrial fibrillation, tibial vein thrombosis, polyneuropathy, pulmonary thromboembolism and a diagnosis of homocystinuria (plasma homocysteine 268 μmol/L) and antiphospholipid syndrome. He started oral anticoagulant, pyridoxine, folic acid, vitamin B12 therapy without benefit. From 56 to 62y: he had: transient ischemic attacks with following dizziness, subarachnoid hemorrhage, partial renal artery thrombosis. The analysis of cystathionine beta synthase, methylenetetrahydrofolate and Transcobalamin II genes did not show mutations. At 63y, urine and plasma analysis showed increased urinary methylmalonic acid (ur.MMA) (2706 mmol/mol creatinine) associated to normal vitaminB12 (789 pg/ml) and hyperhomocysteinemia (357 μmol/L) and a diagnosis of methylmalonic aciduria (MMA) with homocystinuria was done. He started treatment with betaine (up to 21gr/day), hydroxocobalamin (OHCbl; 1 mg/day orally) and a low-protein diet (40 g/day) decreasing dizziness, plasmatic homocysteine (latest value 107 μmol/L) and ur.MMA (latest value 259 mmol/mol creat ur). MMACHC gene analysis showed only one mutation (p.Arg2106Gln), the [1-14 C] propionate uptake in fibroblasts was reduced and normalized in OHCbl-supplemented medium. MMADHC gene analysis is ongoing. Before undertaking expensive genetic testing, a dosage of ur.MMA should be performed when homocystinuria is not associated to a vitamin B12 reduction Since our publication (Tuschl et al, JIMD, 2008) describing two siblings with inherited hypermanganesaemia, dystonia and liver cirrhosis, we have collected data on additional fourteen patients from seven unrelated families. All of these patients have sequence changes in the same gene; expression studies are in progress to confirm they disrupt the function of the gene product. Following normal initial development, patients typically present at the age of two to fourteen years, with gait disturbance and increased muscle tone in the lower limbs. Some patients also have upper limb involvement causing difficulties with fine motor movements. MRI imaging is characteristic with hyperintensity of the basal ganglia on T1 weighted scans and no corresponding abnormality on T2-weighted scans. Laboratory investigations show polycythaemia (Hb 16-22 g/dL) and whole blood manganese level above 2000 nmol/L. The degree of abnormality of liver function varies quite considerably-we have identified two further patients who died of the complications of liver cirrhosis. Chelation therapy plus iron supplementation, as used in the patient under our care, seems to halt progression of liver cirrhosis as well as improve dystonia. This treatable disorder of Mn metabolism needs to be considered in any patient presenting with dystonia or Parkinsonian symptoms.