Dyskeratosis Congenita
Dongyou Liu in Handbook of Tumor Syndromes, 2020
The BM findings in DC are variable and range from normal to different severity of aplasia depending on the stage of the disease. Aplastic anemia occurs in patients with a median age of presentation of 11 years. The anemia is macrocytic. Fetal hemoglobin levels are increased. Approximately 90% have peripheral cytopenia of one or more lineages. Initially, the patient usually presents thrombocytopenia, and during the evolution of the disease this becomes more global and they develop severe BMF. BMF (in up to 90% of patients) is one of the major causes of premature mortality in DC due to opportunistic infections because of the significant reduction in mature blood cells. The BM abnormalities can progress in different forms with the appearance of myelodysplasia in one or more lineages or leukemia. It has been reported that patients with DC have an observed expected ratio of 2663 to develop myelodysplasia (95% confidence interval 858–6215), with a mean age of onset of 35 years.
Hematopoiesis and Storage Iron in Infants
Bo Lönnerdal in Iron Metabolism in Infants, 2020
Several developmental changes occur in the erythropoiesis of the fetus. The site of red blood cell production is primarily in liver tissues by 3 months of gestation age. The bone marrow takes over gradually, starting around 5 months of gestation age (Figure 1). Usually by term of pregnancy, the bone marrow is almost exclusively responsible for erythropoiesis. In preterm newborns, the liver plays a role in red blood cell production even at birth. There are also other developmental changes that occur simultaneously. The size of the red cell gradually becomes smaller during fetal life so that the red cell mean corpuscular volume (MCV) tends to be larger in premature than in full-term newborns. The concentration of hemoglobin seems to rise in the fetus during pregnancy although the details of this development are not well known. Finally, the specific fetal hemoglobin-F is partially replaced by adult hemoglobin-A by term of pregnancy. Thus, premature infants have proportionally more hemoglobin-F than full-term newborns.
The Red Blood Cell In Thalassemia *
Ronald L. Nagel in Genetically Abnormal Red Cells, 2019
Several studies85-87 demonstrated significantly higher 2,3-diphosphoglycerate (2,3-DPG) content and oxygen affinity in a relatively large group of heterozygous thalassemic patients compared with normal controls. Such an increase concerns a compensatory adaptation to the anemia through the 2,3-DPG mediated increase in whole blood p50, which is a shift to the right in the hemoglobin dissociation curve. In patients with homozygous β-thalassemia the increase in 2,3-DPG was much lower than could be expected for their degree of anemia.86-89 It has been hypothesized87 that the greater requirement of ATP in the relatively young thalassemic RBC with normal or high glycolytic activity could cause the prevailing glycolytic flow to avoid the Rapaport and Lubering’s shunt and also cause a consequent decrease in the synthesis of 2,3-DPG. In addition, it is well known that human fetal blood has higher oxygen affinity in comparison with adult blood, a phenomenon normally ascribed to the increased fetal hemoglobin content. Although 2,3-DPG levels in human newborn and adult normal RBC are not significantly different, fetal hemoglobin binds less 2,3-DPG and its in vivo oxygen dissociation curve is shifted to the left when compared with hemoglobin A.90 The increased fetal hemoglobin concentration in most cases with β-thalassemia major appears to account, at least in part, for their inappropriately high blood oxygen affinity.
Hb F-Wentzville [Gγ24(B6)Gly→Glu; HBG2: c.74G>A, p.Gly25Glu]: An Unstable Gγ-Globin Variant Associated with Neonatal Hemolytic Anemia
Published in Hemoglobin, 2020
Katarina M. Semkiu, Jennifer L. Oliveira, Phuong L. Nguyen, Tavanna R. Porter, David B. Wilson
Fetal hemoglobin (Hb F), the principal hemoglobin (Hb) produced by the fetus, is a tetramer composed of two α- and two γ-globin chains [1]. γ-Globins are encoded by the paralogous HBG1 and HBG2 genes. The resultant proteins, Aγ- and Gγ-globin, are nearly identical, differing only in the amino acid at position 136 (alanine vs. glycine) [1]. Gγ is the predominant γ-globin in neonatal erythrocytes (Gγ:Aγ = 7:3) [2]. γ Chain variants may be evident at birth but rapidly disappear over the first months of life owing to globin switching, wherein γ-globin expression is extinguished and adult globin (β, δ) expression is activated [3]. Most γ-globin variants are clinically insignificant, but some cause transient hemolytic anemia, cyanosis or methemoglobinemia [1,3,4]. In this report, we describe a novel Gγ-globin variant associated with neonatal hemolysis.
Distinctive phenotypes in two children with novel germline RUNX1 mutations - one with myeloid malignancy and increased fetal hemoglobin
Published in Pediatric Hematology and Oncology, 2020
Shruti Bagla, Katherine A. Regling, Erin N. Wakeling, Manisha Gadgeel, Steven Buck, Ahmar U. Zaidi, Leigh A. Flore, Michael Chicka, Charles A. Schiffer, Meera B. Chitlur, Yaddanapudi Ravindranath
Based on the emerging use of hypomethylating agents in CMML and more recently in JMML,31,32 treatment was started with two five-day courses of intravenous decitabine (20 mg/m2/dose) four weeks apart. Normoblastemia resolved but there was no objective platelet response and there was a modest increase in CD16+ monocytes (Figure 1C, 1D*). Fetal hemoglobin remained elevated. A trial of valproic acid (50 mg/kg/day) for 7 days was given based on in vitro studies showing increased megakaryocyte ploidy in experimental systems.33,34 Despite this, the patient continued to be transfusion dependent for platelets and red blood cells (RBCs); repeat bone marrow aspirate and biopsy showed clearance of sea blue histiocytes but persistent blast cells and decreased megakaryocytes. Our patient had no full siblings, and her half-sister was not a haplo-match. Therefore, she underwent a 4/6 match umbilical cord blood stem cell transplant. Post HSCT she developed grade IV acute graft-versus-host disease (aGVHD) of her skin, gastrointestinal tract, and liver. She subsequently died after developing disseminated aspergillosis.
Association of Xmn1 polymorphism and consanguineous marriage with fetal hemoglobin in Syrian patients with sickle cell disease
Published in Cogent Medicine, 2019
Fariz Kahhaleh, M Ameen Sulaiman, Faizeh Alquobaili
The ameliorating role of fetal hemoglobin (HbF) in sickle cell disease (SCD) has been well established. Higher levels of HbF associate with a milder phenotype of SCD manifested with a lower number of hospitalizations and higher survival rates (Mpalampa, Ndugwa, Ddungu, & Idro, 2012; Platt et al., 1994). Among SCD patients, HbF concentrations vary from 0.1% to 30% with an average of about 8%, this variation is not fully understood yet (Steinberg, 2005). HbF levels induced by hydroxyurea, a known medication used in SCD treatment, have also shown a high degree of variation (Steinberg et al., 1997; Ware et al., 2002). Many studies have shown that genetic variations at specific DNA locations may explain part of HbF variation at baseline and hydroxyurea-induced levels (Menzel et al., 2007; Roy et al., 2012; Wonkam et al., 2014). The (C-T) variation at position −158 upstream of the Gγ globin gene (HBG2, rs7482144), which is detectable by the restriction enzyme Xmn-1, known to associate positively with HbF levels in SCD adults and children (Cardoso et al., 2014; Dadheech et al., 2014; Pandey, Pandey, Mishra, & Saxena, 2012; Sheehan et al., 2013; Ware et al., 2011).
Related Knowledge Centers
- Fetus
- Hemoglobin A
- Oxygen
- Placenta
- Transport Protein
- Circulatory System
- Uterus
- Hemoglobin
- Red Blood Cell
- Beta Thalassemia