Biochemical and genetic basis of red cell enzyme deficiencies

Enzyme deficiencies have been identified in all erythrocyte pathways. Their frequencies differ with respect to the affected enzyme, the severity of the clinical manifestations and the geographical distribution. Most mutations are found within the coding sequences of genes, missense mutations occurring more often than deletions, insertions, splice site defects or premature stop codons. Promoter mutations are rare. The clinical manifestations are chronic or non-chronic haemolytic anaemias. The first of these are characterized by an impairment of cell function at normal values of the external load parameters kATPase and kGSHox. Haemolysis with a non-chronic course is induced only at enhanced values of the load parameters, caused by free radical generation by oxidative drugs, fava beans, infections, fever and physical exercise. The development of secondary haemochromatosis is the most common cause of mortality in patients suffering from severe chronic non-spherocytic haemolytic anaemia. Intracellular iron deposits must be prevented by timely treatment with effective chelating agents.