Albertine Donker

Chapter 6 218 XLSA patients should not be considered refractory to pyridoxine therapy until iron stores are normalized with serum ferritin and transferrin saturation in the normal range. 11 Because of this mechanism it is feasible to phlebotomize in XLSA, even in patients with severe anemia. Hb typically increases, rather than decreases, after reversal of iron overload by blood removal, as shown by patient 2B en 3. In patients who develop anemia, frequent withdrawal of a small volume is often feasible (our unpublished observations). Although 13 out of 15 patients shared the same missense mutation, response to pyridoxine was highly variable. The reason for this remains unclear. Low compliance should be considered, as was the problem in patient 10. If patients are unresponsive to pyridoxine, it is recommended to discontinue it, since increased levels of pyridoxine are associated with peripheral neuropathy. 35,36 Peripheral neuropathy was not observed in our cases. In conclusion, our case series describes the biochemical and clinical presentation of XLSA patients and the effectiveness of treatment regime, and it illustrates the various pitfalls associated with diagnosis, follow-up and treatment of the disease. We suspect ALAS2 mutations to be more frequent, but not easy to diagnose. The combination of these data with previously published patient information led us to the following recommendations for the clinical management of patients with XLSA: 1. Diagnosis. Consider XLSA in: • Men with unexplained microcytic anemia, even if the anemia is mild, since missing the diagnosis might result in severe iron overload and associated morbidity and mortality. • Men of all ages presenting with the phenotype of MDS with refractory anemia (RA), without MDS specific cytogenetic abnormalities, and microcytosis, because patients with MDS-RA have MCV levels within the reference range. • Women with unexplained microcytic or normocytic anemia because of the possibility of late onset XLSA due to a combination of congenital and acquired unbalanced lyonization. • Patients with unexplained hereditary hemochromatosis and concomitant (mild) microcytic anemia.