Microcytic anemia in a pregnant woman: beyond iron deficiency

Abstract

Sideroblastic anemias are a heterogeneous group of disorders characterized by anemia of varying severity and the presence of ringed sideroblasts in bone marrow. The most common form of inherited sideroblastic anemia is X-linked sideroblastic anemia (XLSA). In many XLSA patients, anemia responds variably to supplementation with pyridoxine (vitamin B6). We describe the case of a pregnant female with XLSA who had a novel mutation on the ALAS2 gene (c.1218G > T, p.Leu406Phe). Oral chelation therapy was contraindicated and high-dose vitamin B6 would have possible side effects in pregnancy. Serum hepcidin level was very low, indicating increased absorption of iron secondary to ineffective erythropoiesis. Therapy was begun with a low dose of pyridoxine that was increased post-partum. The patient's liver showed moderate iron deposits. During a subsequent 3-month period of pyridoxine supplementation, serum ferritin level and transferrin saturation decreased, hemoglobin content and serum hepcidin level normalized, and morphologic red cell abnormalities improved markedly. The patient responded well to treatment, showing the pyridoxine responsiveness of this novel ALAS2 mutation. The baby girl had the same mutation heterozygously, and although she was neither anemic nor showed abnormalities in a peripheral blood smear, she had a mild increment in RDW and her condition is now being followed.

Biology of Heme in Mammalian Erythroid Cells and Related Disorders

“…Typically, XLSA patients are male and present before the age of 40 years; however, this disorder occurs across a broad range of ages and can affect elderly patients [ 74 ]. On the other hand, anemia may also present in heterozygous female carriers, presumably because of skewed X inactivation or the excessive age-related skewing that occurs in hematopoietic tissues [ 75 , 76 ].…”

Sideroblastic anemia: functional study of two novel missense mutations in ALAS2

“…We have previously published this patient (Rollon et al. ). Briefly, a female in her late‐thirties was diagnosed with anemia that became more severe from the onset of pregnancy.…”

“…The patient responded partially to a low dose of pyridoxine during pregnancy and reached a normal Hb level with 60 mg/day after delivery (Rollon et al. ). The red cell abnormalities improved, but did not disappear, despite the restoration of Hb levels, 2 years later (second row on Table ).…”

Missense variants in ALAS2 gene in five patients

“…Hematologists diagnosed patients with SAs based on the presence of ring sideroblasts in the bone marrow aspirate smear. We performed the genetic study in eighteen unrelated patients; some results have yet been published …”