Fetal Globin Induction with Oral Butyrates in β Thalassemia.

The β-thalassemias are characterized by insufficient or absent production of β-globin chains leading to imbalanced a and non a-globin chain synthesis which cause accumulation and precipitation of unpaired a-globin chains and, consequently, to ineffective erythropoiesis and hemolysis. Hb F enhancement could be a therapeutic approach for these patients as it reduces the imbalance between the a and β chains. L-carnitine (L-3-hydroxy-4-N-trimethyl aminobutyric acid) is an oral butyrate derivative that can stimulate Hb F production and stabilize the erythrocyte membrane against oxidative stress. We studied the hematological effects of short term therapy of L-carnitine on the induction of fetal hemoglobin production in a group of β thalassemia patients.

The study was conducted on 27 β-thalassemia patients (age 6-22 years, mean =12.26± 4.25 years). L-carnitine therapy was given orally to the patients in a dose of 50 mg/kg/day for 45 days. Complete blood count, Hemoglobin electrophoresis (by densitometry following cellulose acetate) and F cell percentages (by immuno-histochemical technique using monoclonal anti-Hb A antibodies) were estimated before and after L-carnitine therapy. The drug was well tolerated by all patients. According to the increase in the percentage of Hb F and F cells after treatment, the patients were divided into 2 subgroups; Group 1(responders) those who showed an increase in Hb F and F cell percentage while group 2(non responders) were those who showed either decrease or constant Hb F and F cell percentage after treatment.

In group 1 (14 patients, 51.85%), Hb F increased significantly from 19.3±14.62% to 45.05±17.45% (P=0.00001) and F cell percentage increased from 19.72±14.45% to 43.89±16.85% (P=0.00006) after L-carnitine therapy. In group 2 (13 patients, 48.15%), Hb F significantly decreased from 35.92±34.92% to 32.1±34.16% (P=0.012) and F cell percentage decreased from 36.53±35.73% to 32.5±33.96% (P=0.014). Hemoglobin, hematocrite and all red cell indices increased non-significantly after therapy in both groups except for the red cell distribution width which decreased significantly in groups 1 and 2 (P=0.001, P=0.004 respectively).The intervals between blood transfusions were prolonged in group 1 (3.357±1.216 versus 4.071±1.269 weeks after treatment, P=0.0028) and in group 2 (3.077±1.038 versus 3.615±1.121 weeks, P=0.0028).

L-carnitine as an oral butyrate is a physiologic, well tolerated and safe drug that can stimulate Hb F production in thalassemia patients. Improvement of the hematological parameters in the non responders could be attributed to the other physiologic effects of L-carnitine on the red cells of thalassemia patients. Further longer studies with a larger number of patients and a higher dose of L-carnitine are required to evaluate the overall role of L-carnitine in the course and prognosis of thalassemia.

No relevant conflicts of interest to declare.