582 Δ-AMINOLEVULINIC ACID (ALA) SYNTHETASE DEFECT IN A FEMALE WITH CONGENITAL SIDEROBLASTIC ANEMIA

Abstract

Since birth a 3-year old black girl has had severe refractory hypochromic microcytic anemia. Her usual red blood cell (RBC) values are Hgb 6.0 gm/dl, Hct 20%, Retic. 0.5%, MCV 52 fl, MCH 15 pg. Iron deficiency and clinically significant thalassemia were excluded by: lack of response to oral or parenteral iron, serum Fe/TIBC 231/276 μg/dl and serum ferritin 407 ng/ml; normal hemoglobin electrophoresis, absence of erythroid inclusions in the peripheral blood and bone marrow (BM), α/β globin synthetic ratio of 0.85 in peripheral blood reticulocytes and negative family studies. Intensive erythroid hyperplasia and numerous ring sideroblasts were present in the BM aspirate, and electron microscopy confirmed intramitochondrial deposits of iron. Free RBC protoporphyrin, urine porphyrins and porphyrin precursors, and BM ferrochelatase activity were normal. RBC ALA dehydrase, uroporphyrinogen synthetase and pyridoxal kinase activities were increased. Activity of BM ALA synthetase was markedly reduced to 5.5 pmoles ALA/106 erythroblasts/30 min (normal 127±29) but was enhanced 5-fold by pyridoxal phosphate (normal 0-25% increase). Therapy with oral pyridoxine has thus are not noticeably increased effective RBC production. The sideroblastic anemia in this patient appears to be related to an inherited defect in the initial step of heme biosynthesis.