Effects of iron chelation therapy on the clinical course of aceruloplasminemia: an analysis of aggregated case reports

Background Aceruloplasminemia is a rare genetic iron overload disorder, characterized by progressive neurological manifestations. The effects of iron chelation on neurological outcomes have only been described in case studies, and are inconsistent. Aggregated case reports were analyzed to help delin...

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Vydáno v:Orphanet journal of rare diseases Ročník 15; číslo 1; s. 105 - 8
Hlavní autoři: Vroegindeweij, Lena H. P., Boon, Agnita J. W., Wilson, J. H. Paul, Langendonk, Janneke G.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London BioMed Central 25.04.2020
BioMed Central Ltd
Springer Nature B.V
BMC
Témata:
Aceruloplasminemia
Age
Anemia
Care and treatment
Case reports
Case studies
Chelation
Chelation therapy
Clinical outcomes
Comparative analysis
Deferiprone
Development and progression
Diabetes
Disease
Ethnicity
Health aspects
Hemoglobin
Human Genetics
Inherited metabolic diseases
Iron
Iron chelation therapy
Medical research
Medical treatment
Medicine
Medicine & Public Health
Neurological manifestations
Neutropenia
Neutrophils
Patients
Pharmacology/Toxicology
Phlebotomy
Rare diseases
Netherlands
Neurological manifestations
Deferiprone
Aceruloplasminemia
Iron chelation therapy
Phlebotomy
ISSN:1750-1172, 1750-1172
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Shrnutí:Background Aceruloplasminemia is a rare genetic iron overload disorder, characterized by progressive neurological manifestations. The effects of iron chelation on neurological outcomes have only been described in case studies, and are inconsistent. Aggregated case reports were analyzed to help delineate the disease-modifying potential of treatment. Methods Data on clinical manifestations, treatment and neurological outcomes of treatment were collected from three neurologically symptomatic Dutch patients, who received deferiprone with phlebotomy as a new therapeutic approach, and combined with other published cases. Neurological outcomes of treatment were compared between patients starting treatment when neurologically symptomatic and patients without neurological manifestations. Results Therapeutic approaches for aceruloplasminemia have been described in 48 patients worldwide, including our three patients. Initiation of treatment in a presymptomatic stage of the disease delayed the estimated onset of neurological manifestations by 10 years (median age 61 years, SE 5.0 vs. median age 51 years, SE 0.6, p  = 0.001). Although in 11/20 neurologically symptomatic patients neurological manifestations remained stable or improved during treatment, these patients were treated significantly shorter than patients who deteriorated neurologically (median 6 months vs. median 43 months, p  = 0.016). Combined iron chelation therapy with deferiprone and phlebotomy for up to 34 months could be safely performed in our patients without symptomatic anemia (2/3), but did not prevent further neurological deterioration. Conclusions Early initiation of iron chelation therapy seems to postpone the onset of neurological manifestations in aceruloplasminemia. Publication bias and significant differences in duration of treatment should be considered when interpreting reported treatment outcomes in neurologically symptomatic patients. Based on theoretical grounds and the observed long-term safety and tolerability in our study, we recommend iron chelation therapy with deferiprone in combination with phlebotomy for aceruloplasminemia patients without symptomatic anemia.
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ISSN:1750-1172
1750-1172
DOI:10.1186/s13023-020-01385-w