Intravenous
arginine butyrate has been shown to increase
fetal hemoglobin (HbF) in sickle cell and
thalassemia patients. Recently, we observed that
sodium 4-phenylbutyrate, a
drug administered orally to treat
urea cycle disorders, increases HbF production in nonanemic children and adults. We treated six subjects with
sickle cell disease over a period of 14 to 179 days. All subjects received their initial
therapy of 9 to 13 g/m2/day as 0.5-g
tablets of
sodium 4-phenylbutyrate as inpatients. All subjects showed a rapid increase in the percentage of F-reticulocytes (pretreatment, 1% to 20%; posttreatment, 10% to 44%). Four subjects were treated only 11 to 25 days as inpatients. Two of these four subjects failed to respond to the outpatient component because of their inability to maintain an intake of 30 to 40
tablets per day. One subject (C) developed a
rash at day 10 and discontinued treatment at day 14. Another subject (B) was transfused for a painful crisis on day 25. Subject A, treated for 179 days, has an increased percentage of F cells, from 54% to 77%, and increased HbF levels, from 10.6% to 18%. Subject F, treated for 154 days, has an increased percentage of F cells, from 59% to 73%, and an increased percentage of HbF, from 10.4% to 16%. All subjects showed some increase in weight. Subject A developed mild transient ankle
edema. Myelotoxicity was not seen in any treated patient.
Oral administration of
sodium 4-phenylbutyrate rapidly increases F-cell production in
sickle cell disease.