Introduction: The diagnosis aceruloplasminemia is usually made in patients with advanced neurological manifestations of the disease. In these patients prognosis is poor, disabilities are severe and patients often die young. The aim of our study was to facilitate recognition of aceruloplasminemia at a disease stage at which treatment can positively influence outcome. Currently, the neurological phenotype of aceruloplasminemia has been mainly described in Japanese patients. This 'classical' phenotype consists of cerebellar ataxia, hyperkinetic movement disorders and cognitive decline. In this study we describe the spectrum of neurological disease in Caucasian patients.
Methods: Data on neurological presentation and follow-up were gathered from both our patients, homozygous for the G631R mutation in the . CP gene, and other published Caucasian cases. Neurological features of aceruloplasminemia in Caucasian patients were compared to those summarized in Japanese patients.
Results: 21 Caucasian patients, both ours and the described cases, displayed a wide range of movement disorders with predominant chorea, parkinsonism and ataxia, and also tremor and dystonia. In addition to cognitive decline, nearly half of the Caucasian patients presented with psychiatric changes, including depression, anxiety and behavioral changes. In one-third of the neurologically symptomatic Caucasian patients, cognitive- or psychiatric changes were the first neurological manifestations of aceruloplasminemia.
Conclusions: Aceruloplasminemia in Caucasian patients can present with a wider range and a different order of neurological symptoms than previously described in Japanese patients. Psychiatric changes and parkinsonism can be added to the spectrum of neurological disease. Cognitive- or psychiatric changes may be the first neurological manifestations of aceruloplasminemia.

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Parkinsonism & Related Disorders
Erasmus MC: University Medical Center Rotterdam

Vroegindeweij, L. H. P., Langendonk, J., Langeveld, M., Hoogendoorn, M., Kievit, A. J. A., Di Raimondo, D. (Domenico), … Boon, A. (2017). New insights in the neurological phenotype of aceruloplasminemia in Caucasian patients. Parkinsonism & Related Disorders, 36, 33–40. doi:10.1016/j.parkreldis.2016.12.010