of arsenic in ~ethylen~t~trahydrofolate deficiency
W. Onkenho&,
(Received
15 May. 1992)
recekd
(Accepted
Homocystinuria,
reductase
P.M. Edelbroek”. J.F.M. de Kom”, F.A. de Wolff’ and A.C.B. Peters”
(Rcviscd.
KPJ*WV&:
_ ..___. __
Methyknetetrahydrofolate
5 June.
9 June.
1992)
I992)
reductase: Arsenic: Neurotoxicity
Summary
A l&year-old bilateral
girl from
Babinski
Surinam
signs. Laboratory
presented
with mental
examination
showed
deterioration
and severe
a hyperhomocysteinemia
paraparesis
with areflexia
and
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 methylation. arsenic.
we suggest that the MTHFR only she developed
deficiency
severe clinical
in this girl might explain
signs and symptoms
Introduction
Arsenic
the fact that of all family members
of arsenic
exerts its toxic effects in the human
ruvate and succinate
pathways
of certain Especially
are sensitive
body by enzymes the py-
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
small transverse white (Mees) the lunula of each fingernail. chronic
arsenic
Cbvres~otzdrtzcT to: O.F. Brouwer, Neurology,
MD, Department
University
9hOO. 2300 RC Leiden. The Netherlands.
Hospital
of Neurology.
L&den,
Tel.: (71) 263920.
P.O. Box
poisoning,
lines may appear above We report a girl with
in whom
toms seemed to be aggravated drofolate-reductase (MTHFR)
the clinical
symp-
by 5.1 O-methylenetet~hydeficiency.
Case report
A 16-year-old
of Child
to
peripheral neuropathy [1,2]. Symptoms may occur as part of acute or chronic intoxication. In the latter case,
reacting with the sulfhydryl groups necessary for cellular metabolism.
Division
exposed
poisoning.
girl from Surinam was admitted in August 1989 because of mental deterioration and progressive muscle weakness of both legs since I year. Three months before admission she had some generalized seizures. She was known to be slightly mentally retarded.
30x but she went to a regular was unremarkable. siblings
Her parents
were healthy.
revealed
extreme
paraparesis
Physical
Otherwise
her history
were cousins:
four other
examination
bradyphrenia
(MRC
and bilateral
school.
and
studies
concentration.
revealed
areflexia
acid
was also clearly
B,z plasma
increased
and normal excretion
into
1). Analysis
was diffusely
of
ranging over the
slow, and
were of the
TABLE I LABORATORY DATA IN THE PATIENT (A) AND THE OTHER SIX FAMILY MEMBERS (B) B
Normal value
Ph.SF?lU
Vitamin B , 2 @g/ml) Folic acid (ng/ml) Homocysteine” (m&h)
Increased neurotoxicity of arsenic in methylenetetrahydrofolate reductase deficiency.
A 16-year-old girl from Surinam presented with mental deterioration and severe paraparesis with areflexia and bilateral Babinski signs. Laboratory exa...