Hereditary erythroenzymopathies associated with haemolytic anaemia – their diagnostics in the czech and Slovak populations
Authors:
P. Kořalková 1; R. Mojzíková 1; D. Pospíšilová 2; K. Indrák 3; J. Čermák 4; V. Divoký 1,3
Authors‘ workplace:
Ústav biologie, Lékařská fakulta, Univerzita Palackého v Olomouci
1; Dětská klinika, Lékařská fakulta Univerzity Palackého v Olomouci a Fakultní nemocnice Olomouc
2; Hemato-onkologická klinika, Lékařská fakulta Univerzity Palackého v Olomouci a Fakultní nemocnice Olomouc
3; Ústav hematologie a krevní transfuze, Praha
4
Published in:
Transfuze Hematol. dnes,24, 2018, No. 2, p. 104-114.
Category:
Overview
Hereditary red blood cell (RBC) enzymopathies are genetic disorders affecting genes encoding red blood cell enzymes. They cause a specific type of anaemia designated hereditary nonspherocytic haemolytic anaemia. Enzymopathies affect cellular metabolism, which in the RBC mainly consists of anaerobic glycolysis, the hexose monophosphate shunt, glutathione metabolism and nucleotide metabolism.
Enzymopathies are commonly associated with normocytic/slightly macrocytic normochromic haemolytic anaemia. In general, RBC enzymopathies are not characterized by specific abnormalities in RBC morphology. Routinely used haematology methods are unable to pinpoint a specific enzyme defect. Definitive diagnosis is based on the detection of reduced specific enzyme activity and molecular characterization of the defect at DNA level.
This work represents advanced and up-to-date information regarding RBC enzyme deficiencies in the Czech and Slovak populations dating from the 1980s, when mutations in Czech and Slovak subjects resulting in glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) deficiencies were first described. Both deficiencies represent the most common erythroenzymopathies worldwide. Since 2013, our laboratory has focused on the introduction of direct enzyme assays supplemented by genetic testing in patients with haemolytic anaemia and suspected erythroenzymopathy. To date, several different enzyme defects have been diagnosed in twenty-four patients. Apart from G6PD and PK deficiencies (9 and 12 cases), 2 families with glucose phosphate isomerase (GPI) defect and 1 family with the very rare hexokinase (HK) deficiency have been identified. The two latter deficiencies were diagnosed in the Czech and Slovak populations for the first time. Among the 22 identified mutations, were novel and have not been previously reported in literature:
5, namely G6PD p.(Phe216Tyr), PK p.(Arg518Leufs*12), p.(Asp293Val) and GPI p.(Ser160Pro), p.(Arg472Cys).
Key words:
erythrocytes – haemolytic anemia – enzymopathies
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