Albertine Donker

Chapter 6 214 of this complication. The patient had no history of liver cirrhosis. 18 Because of the family history, mutation analysis of the HFE -gene was also performed in his grandson, which revealed homozygosity for the p.Cys282Tyr mutation. Because of increasing ferritin levels at age 16 years treatment with phlebotomies was started. Within a 30 weeks period, this resulted in a decrease in ferritin levels from 454 μg/L to 72 μg/L and an increase of Hb from 7.4 mmol/L tot 7.8 mmol/L ( Figure 1 ). Patient 3 presented with both severe anemia (4.3 mmol/L) and very severe and systemic iron overload (ferritin of 5040 µg/L) at age 35. Despite his severe anemia, phlebotomies were well tolerated and are likely to have contributed to normalization of his iron stores and Hb in addition to treatment with pyridoxine and iron chelation. In his teens patient 5 presented with severe anemia and ferritin within reference ranges. His younger brother was diagnosed at the age of 23 years with SA by family screening. He had no signs and symptoms of anemia. However, serum ferritin was 1200 µg/L, suggesting severe iron overload. Treatment for SA and iron overload was started, consisting of pyridoxine and phlebotomies. Patient 9 was initially diagnosed with myelodysplastic syndrome (MDS) at the age of 30 years, subtype Refractory Cytopenia with Multilineage Dysplasia (RCMD). Interestingly, no ring sideroblasts were seen in the bone marrow and MCV was low, 70 fL. Since his grandfather had previously been described with “hereditary primary sidero-achrestic anemia” (patient 41 in ref 20 ) and since the index patient presented with a hypochromic microcytic anemia in combination with iron overload, an ALAS2 mutation was suggested and subsequently confirmed.