Movement disorder due to aceruloplasminemia and incorrect diagnosis of hereditary hemochromatosis

Excerpt

Sirs: We read with great interest the paper by Russo and colleagues published in your journal and agree with authors’ conclusion that hereditary haemochromatosis (HH) is unlikely to cause movement disorders [10]. We observed a 56-year-old man affected by diabetes, dementia, ataxia, parkinsonism, and retinal degeneration; MRI showed iron deposition within cerebral deep nuclei. His sister had received a diagnosis of HH some years earlier, so that he was diagnosed of having HH associated with central nervous iron deposition. However, this patient did not manifest any involvement of liver and heart, he had sideropenic anemia, low transferrine saturation and elevated ferritin concentration. Moreover serum ceruloplasmin was undetectable: this, in combination with the clinical picture, led to the diagnosis of hereditary aceruloplasminemia (HA), confirmed later by means of direct analysis of ceruloplasmin gene. The same mutation was also carried by the sister whose diagnosis of HH was therefore incorrect albeit she has been followed up for several years by different hematologists who made the diagnosis on the basis of: high serum ferritin, high iron concentration on liver biopsy specimen, and heterozygous H63D mutation of the HFE gene. HA is a rare autosomal recessive disease caused by the absence of ceruloplasmin, a ferroxidase which catalyses the oxidation of ferrous to ferric iron, a change required for release of iron to transferrin [12]. It is classified among the group of Neurodegenerations with Brain Iron Accumulation (NBIA) along with Karak syndrome [8], Neuroferritinopathy [3], and PKAN, formerly known as Hallervorden-Spatz disease [6]. NBIA have to be distinguished from Wilson’s disease, characterized by abnormal copper depositions and low serum ceruloplasmin concentration, due to mutations in the gene encoding ATP7B, the protein that contributes to copper incorporation into apoceruloplasmin [7]. …