Concomitant a novel ALAS2 mutation and GATA1 mutation in a newborn: a case report and review of the literature

Abstract

GATA-1, an X-linked gene, encodes a transcription factor that plays a role in erythropoiesis and megakaryopoiesis. GATA-1 mutations have been associated with various diseases, such as X-linked thrombocytopenia. ALAS2 is an X-linked erythroid-specific isoenzyme expressed during erythropoiesis. Mutations of ALAS2 were associated with X-linked sideroblastic anemia. We report a case of newborn twin boy with anemia and thrombocytopenia at birth. A bone marrow biopsy at 4 months of age showed marked dyserythropoiesis, dysmegakaryopoiesis, and rare ringed sideroblasts. Gene sequencing study showed a previously reported mutation in GATA-1 at c.622G>A location (G208R) and a novel ALAS2 mutation at c.1436G>A location (R479Q).

Keywords: ALAS2 mutation; GATA1 mutation; dyserythropoiesis; dysmegakaryopoiesis; macrothrombocytopenia; ringed sideroblasts.

Figure 1

Comparison of peripheral blood and bone marrow morphology at 2 months (A) and 4 months of age (B). In panel A: Top left: Peripheral blood showed normocytic RBCs without anisopoikiocytosis. A very rare agranular large platelet is seen (MPV 10.3). Top right: Bone marrow aspirate showed trilineage hematopoiesis with marked erythroid hypoplasia. The megakaryocytes appeared unremarkable. Bottom left: Iron stain on the bone marrow aspirate showed a rare ringed sideroblast. Bottom right: Occasional early stage myeloid cells contained small cytoplasmic vacuoles. In panel B: Top left: Peripheral blood showed normocytic anemia with marked anisopoikilocytosis. The insert showed the presence of one of the many RBCs with coarse basophilic stippling. There were many giant agranular platelets (MPV 12.9). Top right: The bone marrow aspirate showed moderate dyserythropoiesis with increased monolocated/hypolobated megakaryocytes with eccentrically located nucleus (insert). Bottom left: The bone marrow showed increased iron storage for age with rare ringed sideroblasts (insert). Bottom right: The bone marrow core biopsy showed the presence of the small megakaryocytes with crescent shaped eccentrically located nuclei.

Figure 2

Hemoglobin, platelet count and transfusion requirements over time. The patient’s platelet count (solid line) and hemoglobin concentration (dashed line) over time until the age of 240 days (8 months) are shown. Transfusion of packed red cells (Δ) and platelets (x) over time are also displayed on these curves.