Dyserythropoiesis and Congenital Dyserythropoietic Anaemias

144

145

Key Points• In P falciparum-infected anemic children, immature gametocytes are more prevalent and abundant in bone marrow than in peripheral blood.• P falciparum-infected anemic children are gametocyte carriers that can potentially contribute to malaria transmission.Plasmodium falciparum immature gametocytes are not observed in peripheral blood. However, gametocyte stages in organs such as bone marrow have never been assessed by molecular techniques, which are more sensitive than optical microscopy. We quantified P falciparum sexual stages in bone marrow (n 5 174) and peripheral blood (n 5 70) of Mozambican anemic children by quantitative polymerase chain reaction targeting transcripts specific for early (PF14_0748; PHISTa), intermediate (PF13_0247; Pfs48/45), and mature (PF10_0303; Pfs25) gametocytes. Among children positive for the P falciparum housekeeping gene (PF08_0085; ubiquitin-conjugating enzyme gene) in bone marrow (n 5 136) and peripheral blood (n 5 25), prevalence of immature gametocytes was higher in bone marrow than peripheral blood (early: 95% vs 20%, P < .001; intermediate: 80% vs 16%; P < .001), as were transcript levels (P < .001 for both stages). In contrast, mature gametocytes were more prevalent (100% vs 51%, P < .001) and abundant (P < .001) in peripheral blood than in the bone marrow. Severe anemia (3.57, 95% confidence interval 1. 49-8.53) and dyserythropoiesis (6.21, 95% confidence interval 2.24-17.25) were independently associated with a higher prevalence of mature gametocytes in bone marrow. Our results highlight the high prevalence and abundance of early sexual stages in bone marrow, as well as the relationship between hematological disturbances and gametocyte development in this tissue. (Blood. 2014;123(7):959-966)

Section: Bone Marrow Smear Examinationmentioning

confidence: 99%

Molecular evidence for the localization of Plasmodium falciparum immature gametocytes in bone marrow

Aguilar

Magallon-Tejada

Achtman

et al. 2014

144

145

“…5 The gene mutated in the majority of CDA I patients (CDAN1) was cloned 6 but the pathogenesis of the disease and the role of the encoded protein codanin-1 are still unknown. Most patients although transfusion-independent develop iron overload; 3,4 however, the details of iron overload regulation in this disease have not been extensively studied, with hepcidin levels (urinary) determined previously in only 2 patients. 7 To determine whether the elevation in serum GDF15 is unique for thalassemia or more generally associated with ineffective erythropoiesis and associated iron loading, we determined the …”

Section: Introductionmentioning

confidence: 99%

“…3 CDA type I (CDA I) is an autosomal recessive subtype with moderate to severe macrocytic anemia, binuclearity, internuclear chromatin bridges, and spongy heterchromatin of late erythroblasts. 3,4 The disease has been described sporadically worldwide as well as in genetic isolates, including Israeli Bedouins. 5 The gene mutated in the majority of CDA I patients (CDAN1) was cloned 6 but the pathogenesis of the disease and the role of the encoded protein codanin-1 are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Elevated growth differentiation factor 15 expression in patients with congenital dyserythropoietic anemia type I

Tamary

Shalev

Perez-Avraham

et al. 2008

122

Congenital dyserythropoietic anemia (CDA) is a rare group of red blood cell disorders characterized by ineffective erythropoiesis and increased iron absorption. To determine whether growth differentation factor 15 (GDF15) hyper-expression is associated with the ineffective erythropoiesis and iron-loading complications of CDA type I (CDA I), GDF15 levels and other markers of erythropoiesis and iron overload were studied in blood from 17 CDA I patients. Significantly higher levels of GDF15 were detected among the CDA I patients (10 239 ؎ 3049 pg/mL) compared with healthy volunteers (269 ؎ 238 pg/mL). In addition, GDF15 correlated significantly with several erythropoietic and iron parameters including

“…At least 3 or 4 new categories have been proposed, designated as IV (CDA with nonspecific erythroid dysplasia), V (congenital ineffective erythropoiesis without significant dysplasia), VI (vitamin B 12 -and folate-independent megaloblastic and dysplastic erythropoiesis), and CDA with intraerythroblastic precipitation of a nonglobin protein, although many cases remain to be classified in a subgroup of CDA. 2 Bone marrow transplantation (BMT) has been used to treat severe congenital erythroid disorders such as major thalassemias or hemoglobinopathies, and BMT is now considered as a potential curative option for many patients with transfusiondependent disorders.…”

Section: Introductionmentioning

confidence: 99%

Hydrops fetalis–associated congenital dyserythropoietic anemia treated with intrauterine transfusions and bone marrow transplantation

Remacha

Badell

Pujol-Moix

et al. 2002

Hydrops fetalis is rarely caused by congenital dyserythropoietic anemia (CDA). We report a patient with hydrops fetalis as a result of severe anemia. This patient needed intrauterine transfusions from 21 weeks of gestation until birth. The hematologic study showed an atypical CDA (hydrops fetalis-associated CDA) characterized by features resembling CDA type II, but negative acidified serum lysis test (HEMPAS negative). The patient was regularly transfused for a year, after which an allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling was successfully carried out. His actual hemoglobin is 127 g/L, and he has not received transfusions for more than a year. In conclusion, intrauterine transfusions and BMT could cure an otherwise lethal atypical CDA. (Blood. 2002;100:356-358)