Vitamin B12-responsive neonatal megaloblastic anemia and homocystinuria
with associated reduced methionine synthase activity
LJ Hallam, M Sawyer, AC Clark and MB Van der Weyden
We present findings on an infant with neonatal megaloblastic anemia,
homocystinuria, and neurologic dysfunction that included developmental
delay and tonic seizures. There was no methylmalonic aciduria.
Cyanocobalamin therapy was accompanied by complete hematologic and
neurologic recovery, diminished homocystine excretion, and subsequently
normal neurologic development. Cultured fibroblasts and lymphoblasts showed
a reduced methionine synthase activity and a growth requirement for
methionine. Cobalamin incorporation by the patient's lymphoblasts was
normal, but the proportion of cellular methylcobalamin in the patient's
lymphoblasts and fibroblasts were markedly reduced and that of
adenosylcobalamin normal. The reduced methionine synthase activity was
independent of assay reducing (thiol) conditions, but normal levels of
activity accompanied culture of the patient's lymphoblasts in medium with
markedly increased cobalamin concentration. The characteristics of the
reduced methionine synthase of our patient differ significantly from that
of the previously described infant with cobalamin E disease and suggest
that genetic heterogeneity may characterize this mutation.
Volume 69,
Issue 4,
pp. 1128-1133,
04/01/1987
Copyright © 1987 by The American Society of Hematology
