Köln's unstable hemoglobin: case report and literature review

Abstract

Unstable hemoglobins are a group of genetic variants of hemoglobins caused by the mutation of amino acids into alpha and beta globins and, depending on the points and types of mutation, the result can vary from no clinical symptomatology to severe hemolytic anemia. On the present report, we study the case of a female patient who showed a very exuberant hematological picture for the red series, which suggests hemoglobinic changes; this was confirmed following the conduction of the protocol established by Laboratório Médico Santa Luzia for the study of hemoglobinopathies and which was then sent for a reference laboratory: C.D.A. Naoun Laboratórios de Análises Clínicas Hemoglobinopathies Unstable hemoglobin Köln HB Due to the great diversity of mutation points on the globinic structure, as well as the types of mutation by substitution or deletion of amino acids, the unstabilizing forms vary greatly. In this situation, some hemoglobins are discreetly unstable and are not

Crystal Structures of HbA2 and HbE and Modeling of Hemoglobin δ4: Interpretation of the Thermal Stability and the Antisickling Effect of HbA2 and Identification of the Ferrocyanide Binding Site in Hb

“…Due to the loss of the hydrogen bond with the 26th residue, the side chain of His117 β flips and its NE2 atom now interacts with another water molecule (not shown in the figure). Previous studies on hemoglobin instabilities suggest that HbE can be unstable when subjected to an increase in temperature ( , ). Our structural studies show that, although there is no direct hydrogen bond between helices B and G near the mutation site of HbE (Figure b), the intersubunit contacts remain the same as those of HbA, presumably due to the presence of the water network that partially connects helices B and G. Among these water molecules, only W2 and W3 are buried, while the other members of this network are on the surface.…”

“…Thermal denaturation experiments performed on blood from E/β-thalassemics in the temperature range of 39-41 °C showed the instability of HbE, a finding that was also observed in homozygous HbE (14). Pscheidt et al (15) also showed the instability of HbE by performing a heat test at 50-60 °C, and they suggested that, in particular, any change that reduces the contacts between the subunits that compose the hemoglobin would generate its instability.…”

Targeted Next Generation Sequencing (NGS) to Diagnose Hereditary Hemolytic Anemias

“…Unstable hemoglobins are a group of genetic variants of hemoglobins in which the mutation of amino acids into alpha and beta globins affect the structure of the molecule, making it unstable. Some hemoglobins are discreetly unstable and are not associated with clinical symptoms, while other unstable hemoglobins precipitate with great intensity, causing hemolytic anemia, excretion of "free heme" such as dipyrroles, making the patient's urine dark 4 . Kӧln haemoglobin was first described by Pribilla et al in 1965, where they found a "new" haemoglobin in haemoglobin electrophoresis, forming a small band between HbA and HbA2, constituting around 5% of total haemoglobin.…”

Common Clinical Manifestations and a Rare Diagnosis: A Case Report of Hemoglobin Köln in Saudi

“…1 Patients with Hgb Köln typically have reticulocytosis, splenomegaly, bilirubin, jaundice, and prolonged dark urine excretion in addition to moderate hemolytic anemia. 2 Prolonged thrombocytopenia or priapism were also reported in certain cases. 3,4 Hemoglobin Köln reports are more common among several regions of the Orient, and throughout Europe.…”