Albertine Donker

X-linked Sideroblastic Anemia in the Netherlands 213 6 (cysteine) and mutant amino acids (tyrosine) differed in size. The wild type residue was buried in the core of the protein; the mutant residue was bigger and probably not fitting. The hydrophobicity of the wild type and mutant residue differed. The mutation probably caused loss of hydrophobic interactions in the core of the protein”. The fact that both brothers share the same mutation and have similar phenotypes suggested the mutation to be pathogenic. Case descriptions Table 1 shows hematological, biochemical, molecular data and treatment characteristics of the XLSA patients. We will describe some of these patients and relatives in more detail in order to illustrate the biochemical and clinical presentation of XLSA patients, the effectiveness of treatment regimens and the various pitfalls associated with the management of this disease. Patient 1A illustrates that women may develop a phenotype of XLSA later in life. At the age of 78 years SA was diagnosed after she presented with anemia (Hb 6.0 mmol/L). Three years earlier, her Hb was 7.7 mmol/L. Post mortem she was found to have the same ALAS2 defect as her son (patient 1B). Patient 2A was originally diagnosed with iron overload at the age of 38 years. 18 Treatment with phlebotomies was started. Because of low Hb levels and ferritin levels within the reference range, phlebotomies were stopped at the age of 51 years. After the discovery of the HFE gene in 1996, at the age of 57 years, the patient was tested for hereditary hemochromatosis (HH). A heterozygous p.Cys282Tyr mutation in the (hemochromatosis) HFE gene was found. Based on this finding, the patient’s iron overload was attributed to HH. However, HH is an autosomal recessive inherited disorder and complications due to iron overload alone are extremely rare in individuals who are heterozygous for defects in the HFE gene. 19 In the same period, a male grandchild (patient 2B) was diagnosed with SA. DNA analysis in this child revealed a p.Arg452His mutation in the ALAS2 gene, responsible for XLSA. The same mutation was subsequently found in his grandfather. So, in retrospect, patient 2A suffered from XLSA with secondary systemic iron overload due to ineffective erythropoiesis. At age 70 years liver biopsy revealed an HCC with substantial iron accumulation in the hepatocytes and some steatosis. The lesion was attributed to iron overload and was not resectable. At age 71 years the patient died