Abstract
In this study the TGA/Chemometric test was applied for diagnosis of a case of congenital hemolytic anemia for which the common first level diagnostic tests were not able to find the erythrocyte congenital defect. A 6 years old girl presented chronic hemolytic anemia characterized by hyperbilirubinemia, increased spleen, negative Coombs tests, normal hemoglobin values, decreased mean corpuscular volume (MCV), increased red cell distribution width (RDW), reticulocytes and lactate dehydrogenase (LDH), and altered erythrocyte morphology (ovalocytes, spherocytes, and rare schizocytes). The diagnostic protocols for differential diagnosis of hereditary hemolytic anemia were carried out by the investigation of the congenital hemolytic anemias due to defects of membrane proteins and the most common erythrocyte enzymes, but no defect was found. The TGA/Chemometric test was applied and the PLS-DA model of prediction was used to process results. The thermogravimetric profile of the patient was very distinct from those of healthy subjects and comparable with those of thalassemia patients. The classification model applied to the patient identified a chronic hemolytic anemia due to a hemoglobin defect and the molecular characterization confirmed the TGA/Chemometrics results, demonstrating the presence of a very rare hemoglobin variant Hb Bibba (α2136(H19)Leu → Proβ2). In conclusion the TGA/Chemometric test proved to be a promising tool for the screening of the hemoglobin defects, in a short time and at low cost, of this case of congenital hemolytic anemia of difficult diagnosis. This method results particularly suitable in pediatric patients as it requires small sample volumes and is able to characterize patients subjected to transfusion.
Highlights
The differential diagnosis of hereditary hemolytic anemias (Haley, 2017) is generally carried out by applying different diagnostic protocols depending on the specific congenital erythrocyte defects such as hereditary erythrocyte enzyme deficiencies (Grace and Glader, 2018), red blood cell counts (RBC) membrane proteins defects (King and Zanella, 2013), or hemoglobinopathies (Cao and Galanello, 2010).Hemoglobin disorders are characterized by pathologic defects on globin chain synthesis: quantitative defects that give rise to thalassemia; qualitative defects, Thermogravimetric Analysis (TGA)/Chemometric Test for Rare Hemoglobin Variants namely hemoglobinopathies, that are due to structural hemoglobin variants; hereditary persistence of fetal hemoglobin
Hemoglobin disorders are characterized by pathologic defects on globin chain synthesis: quantitative defects that give rise to thalassemia; qualitative defects, TGA/Chemometric Test for Rare Hemoglobin Variants namely hemoglobinopathies, that are due to structural hemoglobin variants; hereditary persistence of fetal hemoglobin
The full blood count revealed a decrease in the RBC, Hb, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) values, an increase in the red cell distribution width (RDW) value and reticulocytes count, while the peripheral blood smear showed anisopoikilocytosis and the presence of ovalocytes, spherocytes, schistocytes, and dacryocytes suggesting congenital alterations of erythrocyte morphology
Summary
Hemoglobin disorders are characterized by pathologic defects on globin chain synthesis: quantitative defects that give rise to thalassemia (mainly α and β thalassemia); qualitative defects, TGA/Chemometric Test for Rare Hemoglobin Variants namely hemoglobinopathies, that are due to structural hemoglobin variants; hereditary persistence of fetal hemoglobin. These globin defects determine a wide array of heterogeneous thalassemia syndromes and related diseases. There do exist silent β thalassemic mutations with normal HbA2 levels or borderline elevated HbA2 values of difficult interpretation (Weatherall and Clegg, 2001) These methods need equipment, time and personnel with expertise in the interpretation of the screening results. A positive screening test still needs to be confirmed by molecular analysis of the globin genes (Cao et al, 2002; Giardine et al, 2014)
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