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Metabolic persistence of fetal hemoglobin
JA Little, NJ Dempsey, M Tuchman and GD Ginder
Department of Medicine, University of Minnesota, Minneapolis, 55455, USA.
Hereditary persistence of fetal hemoglobin (HPFH) has typically been
ascribed to mutations in the beta-globin gene cluster. Pharmacologic
agents, including the short-chain fatty acid butyrate, have been shown to
upregulate fetal and embryonic globin gene expression. In this report we
investigate the possibility that metabolic derangements characterized by an
inability to metabolize another short-chain fatty acid, propionate, could
be associated with a persistence of fetal hemoglobin unrelated to
alterations in the beta-globin cluster. Embryonic globin gene upregulation
in a murine adult erythroid cell culture was shown by RNase protection
after induction with three short- chain fatty acids (C2-C5). Chart reviews
and measurement of fetal hemoglobin in five patients with abnormalities in
propionate (C3) metabolism were undertaken; SSCP/dideoxy fingerprint
analysis of the gamma-globin gene promoters was done in three of these five
patients. Twelve patients with other metabolic derangements served as
controls. Only the four patients with clinically severe abnormalities in
propionate metabolism (ages 2 to 11), but without anemia, showed a
sustained elevation in fetal hemoglobin (3% to 10%). The level of elevation
of fetal hemoglobin in these patients, who lack erythropoietic stress,
suggests that propionic acid and/or its metabolites are potent stimulators
of fetal hemoglobin expression. Study of this group of patients should
allow unique insights into the long-term effects of sustained exposure to
elevations of short-chain fatty acid levels.
Volume 85,
Issue 7,
pp. 1712-1718,
04/01/1995
Copyright © 1995 by The American Society of Hematology
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