Methionine Synthase Deficiency (cblG): A Rare Cause of Adult Onset Leukoencephalopathy with Reversible Neurological Deficit (P01.124)

Abstract

Objective: To describe a very rare cause of leucoencepahlopathy with adult onset. Background The presentation of cobalamin (cbl) metabolism disorders has usually been in the first 2 years of life. Design/Methods: A woman complained of pain of the lower limbs at the age of 23. A severe macrocytosis without anemia was observed few years before neurological complain with normal serum folate and vitamin B12 concentrations. At 24 years of age, mild paraparesis appeared subacutely then worsened progressively. Brain MRI showed periventricular leukoencephalopathy. She was considered as having possible multiple sclerosis but cerebrospinal fluid analysis was normal without oligoclonal bands. Results: At the age of 27, a second brain and spinal cord MRI showed moderate cerebral atrophy with periventricular leukoencephalopathy and cervical thinning of spinal cord. Neuro-ophthalmologic examination showed bilateral optic neuropathy. Extensive metabolic analyses in search for metabolic leukodystrophies were negative. Further screening for metabolic disorders revealed hyperhomocysteinemia with hypomethioninemia in the absence of methylmalonic acid upon chromatography. The abnormalities were thought to be due to a defect in homocysteine remethylation. Complementation studies upon cultured fibroblasts indicated a cblG defect rather than a cblE defect. Therapy with intra-muscular hydroxycobalamine and oral betaine was started resulting in normalization of plasma and urine homocysteine concentrations and MCV. Neurological improvement became significant at 3 months. Brain MRI performed respectively at 6 months, 5 years and 7 years of treatment showed an overall stabilization of T2 lesion load but with a slight posterior reduction of periventricular leucopathy. After a review of the literature, we only found 1 case of methionine synthase cblG deficiency with adult onset. Conclusions: In the diagnosis work-up of a adult-leukoencephalopathy, association of homocystinuria and hypomethionemia in the absence of methylmalonic aciduria, should make consider methylcobalamin deficiency due to cobalamin E (cblE) or G (cblG). Disclosure: Dr. Outteryck has received personal compensation for activities with Biogen Idec, Bayer Schering, Teva Neuroscience, Merck & Co., Inc., and Sanofi-Aventis Pharmaceuticals, Inc. Dr. De Seze has received personal compensation for activities with Bayer Schering, Biogen Idec, LFB, Merck Serono, Novartis, Sanofi-Aventis, and Teva Neuroscience.Dr. De Seze has received personal compensation in an editorial capacity for Elsevier. Dr. Stojkovic has received personal compensation for activities with Biogen Idec, Bayer Schering Pharma, Teva, Merck, Sanofi, and LFB. Dr. Delalande has nothing to disclose. Dr. Lacour has received personal compensation for activities with LFB, Genzyme, Biogenidec, Merck, Bayer Schering Pharma, Teva, and Sanofi as a consultant. Dr. Fowler has nothing to disclose. Dr. Vermersch has received personal compensation for activites with Merck Serono, Bayer Schering, Teva-Aventis, Biogen Idec, Allmirall, and Novartis as a consultant and/or speaker.