Rare red blood cell abnormalities

The aim of this thesis is to give insight in the process of diagnosing rare red blood cell defects, to clarify the relation of a defect with cell function and to extend, in this respect, our knowledge about normal red cell function and biochemistry. It is possible to categorize different red cell abnormalities with respect to the functions that are impaired in patients: I) Abnormal hemoglobins and abnormal hemoglobin synthesis. II) Enzyme deficiencies. The lack of enzyme activity can have impact on the energy supply, on the protection against oxidative stress or on both. III) Membrane and cytoskeleton defects. The chapters in this thesis are organized according to these categories, and the introduction section of each chapter provides a more detailed description of the defect in general terms. Each chapter includes several publications studying the molecular cause in depth and its relation to cell functionality of some rare red blood cell abnormalities The remark made about 20 years ago by Dr. Ernest Beutler that he - although a specialist and the ‘godfather’ of red blood cell diagnostics and research - could only solve about 20 percent of the rare cases of anemia that were referred to his laboratory, should make us humble in the expectations that we raise in doctors and patients, but decisive in the implementation of new diagnostic and research tools to reduce the number of unsolved cases of anemia.