C’linimf ~Vewoict,~,~~ m/ Nezmsurgc~r~, 94 ( 1992) 307 3 10 0 I992 Elsevier Science Publishers B.V. All rights reserved 031%8467/92/$05.00 307 Cl.INEU 002 I2 -- -- Case report --~ -.--.---__-...~~_ _ ..___. _ _ Increased neurotoxicity of arsenic in ~ethylen~t~trahydrofolate reductase deficiency O.F. Brouwer”, W. Onkenho&, P.M. Edelbroek”. J.F.M. de Kom”, F.A. de Wolff’ and A.C.B. Peters” (Received 15 May. 1992) (Rcviscd. recekd 5 June. 1992) (Accepted 9 June. I992) KPJ* WV&: Homocystinuria, Methyknetetrahydrofolate reductase: Arsenic: Neurotoxicity Summary A l&year-old girl from Surinam presented with mental deterioration and severe paraparesis with areflexia and bilateral Babinski signs. Laboratory examination showed a hyperhomocysteinemia that was caused by 5,1 O-methylene- tetrahydrofolate reductase (MTHFR) deficiency. In addition. urine samples contained large amounts of arsenic. An open bag with the pesticide copper acetate arsenite was found to be the source of exposure. In remethylation defects such as MTHFR deficiency. the concentration of methyldonors is severely reduced. As arsenic is detoxified by methyl- ation. we suggest that the MTHFR deficiency in this girl might explain the fact that of all family members exposed to arsenic. only she developed severe clinical signs and symptoms of arsenic poisoning. Introduction Arsenic exerts its toxic effects in the human body by reacting with the sulfhydryl groups of certain enzymes necessary for cellular metabolism. Especially the py- ruvate and succinate pathways are sensitive to disrLlption by arsenic. Arsenic anions can substitute for phosphate in many reactions and disrupt oxidative phosphorylation by replacing stable phosphoryl with less stable arsenyl compounds [l]. The effects of arsenic poisoning on the nervous system are those of an encephalopathy and/or Cbvres~otzdrtzcT to: O.F. Brouwer, MD, Department of Neurology. Division of Child Neurology, University Hospital L&den, P.O. Box 9hOO. 2300 RC Leiden. The Netherlands. Tel.: (71) 263920. peripheral neuropathy [1,2]. Symptoms may occur as part of acute or chronic intoxication. In the latter case, small transverse white (Mees) lines may appear above the lunula of each fingernail. We report a girl with chronic arsenic poisoning, in whom the clinical symp- toms seemed to be aggravated by 5.1 O-methylenetet~hy- drofolate-reductase (MTHFR) deficiency. Case report A 16-year-old girl from Surinam was admitted in Au- gust 1989 because of mental deterioration and progres- sive muscle weakness of both legs since I year. Three months before admission she had some generalized sei- zures. She was known to be slightly mentally retarded.