Congential defect in folic acid absorption

Abstract

A Caucasian girl was noted to have persistent diarrhea and progressive pallor since age of two months. Hematologic evaluation at 3 months revealed anemia of 6.0 gm/100 ml and severe megaloblastic erythropoiesis. She failed to respond to oral treatment with folic acid, but she had a prompt hematologic and gastrointestinal response with folic acid I.M. She remained free of anemia and diarrhea and kept growing and developing adequately while receiving parenteral therapy with folic acid. Anorexia and severe stomatitis and glossitis developed regularly three to four weeks after the administration of 15 mg of folic acid I.M. Evaluation at age 11 yrs., 3 weeks after the last dose of folic acid I.M., revealed a normal girl except for moderate stomatitis and glossitis and some hypersegmented PMN leukocytes. Her serum and whole blood folates were 2.0 and 60 ng/ml, respectively, and the serum B-12 was 500 pg/ml. Intestinal absorption tests were normal. Gastric and jejunal biopsies revealed normal mucosa. Folic acid and citrovorum factor absorption tests with 5 mg doses showed flat curves. Forty mg. of folic acid orally also failed to produce an increase in serum folate or to control the early signs and symptoms of folic acid deficiency. The clearance of folate after the administration of 5 mg. of folic acid intravenously was normal, but the urinary excretion of folate was unusually low (100 μgm) in 8 hours. Studies for the presence of a folate inhibitor in the plasma were negative. These studies demonstrate an alteration in the normal mechanism of absorption of both physiologic and pharmacologic doses of folate compounds and suggest also a defective metabolism of folate in the tissues.