PS1296 ERYTROCYTAPHERESIS IN ACERULOPLASMINEMIA PREVENTS PROGRESSION OF CEREBRAL IRON ACCUMULATION AFTER CHELATOR‐INDUCED NORMALIZATION OF IRON STORES
Authors: M. Van Gelder, W. Moris, E. Rombout‐Sestrienkova, C. van Deursen, G. Koek
Journal: HemaSphere (2019)

Background: Hereditary aceruloplasminemia (HA) is a rare autosomal recessive disorder. It comprises mutations in the ceruloplasmin genes leading to the absence of ceruloplasmin, a protein required for iron oxidaztion that enables incorporation into transferrin. Due to diminished iron export from storage cells and a usually mild anemic state due to ineffective iron incorporation, iron absorption is increased resulting in the accumulating of iron in parenchymal cells like hepaocytes, insulin producing pancreatic cells and neurons in the brain that may resultin diabetes, anaemia, retinal degradation and neurological disorders (symptomatic penetrance is high but not 100%).. Several case reports illustrate that iron chelating theray (ICT), when appropriately dosed, may result in normaliztaion of live iron content and iron storage, but a decrease in cerebral iron content has not been observed. The follow‐up of most studies is also short (1 year or less). Only two case reports describe that the iron content in the brain remainded stable for 4 and 13 year during treatment with ICT without any neurological symptoms. Aims: We hypothesized that progressive accumulation of iron in the brain may also be prevented by applying erythrocytapheresis (EA) after normalization of physiological iron stores by ICT. In this way, a continuous increased demand for maximal erythropoiesis by erythrocytapheresis (EA) is induced that may result in the immediately utilization of every absorbed iron atom by the bone marrow and preventingparenchymal accumuation. Methods: A HA patient with a low normal haemoglobin, insulin‐dependent diabetes and no neurological symptoms, is treated with EA for six years now, after normalizing ferritin levels and liver iron with ICT; cerebral iron depostits were not depleted by ICT. Results: This controlled removal of erythrocytes created an enduring asymptomatic low haemoglobin level (around 10 g/dl,), ferritin level within the normal range (mean ferritin of 199 ± 60.9 μg/L before every EA). The liver iron content measured by MRI remained at the same normal level as reached after ICT, and the cerebral iron content, which was not diminished after iron chelation, remained stable. No neurological symptoms have appeared so far. Summary/Conclusion: EA appears to be an elegant therapy to prevent iron accumulation in the brain after inducing normal iron stores by ICT. The advantage of this approach is that prolonged exposure to ICT and its possible occurring medical and definite financial side effects can be avoided. The application of EA allows for controlled haemoglobin reduction preventing symptoms from anaemia. It remains unsure if this strategy prevented the development of neurological or cognitive symptoms, because the prevalence of these is not 100%. On the other hand does this therapy not harm the patient and may be effective. It may be worthwhile to attemnpt this approach in similar cases and even in those that already developed neurological and/or cognitive sequalae.