Aceruloplasminaemia: A Family with a Novel Mutation and Long-Term Therapy with Deferasirox

Lindner, Uwe; Schuppan, Detlef; Schleithoff, Lothar; Habeck, Jörg-Olaf; Grodde, T.; Kirchhof, Klaus; Stoelzel, U.

doi:10.1055/s-0034-1383650

Cited by 11 publications

(8 citation statements)

References 26 publications

(38 reference statements)

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“…Table 2 summarizes the clinical characteristics of all 48 cases treated for aceruloplasminemia, differentiated between neurologically symptomatic patients (n = 24) and patients who started treatment before the onset of neurological manifestations (n = 24). These neurologically asymptomatic patients were diagnosed following the onset of diabetes and/or anemia [7,17,22,28,43,47], during the diagnostic workup of unexplained hyperferritinemia with low transferrin saturation [8,17,20,23,39,43,46,47], or by family counselling [16,21,24,25,27,31,37,42].…”

Section: Review Of the Literaturementioning

confidence: 99%

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

Vroegindeweij

Wilson

Langendonk

2020

Orphanet J Rare Dis

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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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Section: Review Of the Literaturementioning

confidence: 99%

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

Vroegindeweij

Wilson

Langendonk

2020

Orphanet J Rare Dis

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“…We compared the present case with previous ones, limited to those referring to iron chelation therapy (Table) (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Neurological symptoms were improved in 5 of 10 cases (50%), including ours.…”

Section: Discussionmentioning

confidence: 95%

Deferasirox Might Be Effective for Microcytic Anemia and Neurological Symptoms Associated with Aceruloplasminemia: A Case Report and Review of the Literature

et al. 2020

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The patient was a 64-year-old man presented with difficulty in walking, articulation, and swallowing, as well as cognitive impairment. He had refractory microcytic anemia and diabetes mellitus. His serum levels of iron, copper, and ceruloplasmin were low. Magnetic resonance imaging suggested iron deposition in the basal ganglia, thalami, cerebellar dentate nuclei, and cerebral and cerebellar cortices. He was diagnosed with aceruloplasminemia after a ceruloplasmin gene analysis. Iron chelation therapy with deferasirox improved his anemia and cerebellar symptoms, which included dysarthria and limb ataxia. The present study and previous reports indicate that cerebellar symptoms with aceruloplasminemia might respond to deferasirox in less than one year.

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“…(Meral Gunes et al 2014) A 20-year-old patient in Australia was treated for a sustained increase in ferritin and a mild increase in alanine aminotransferase, he was eventually diagnosed with ACP through clinical manifestations. (Lindner et al 2015) In another case, a Japanese woman suffered from anemia at the age of 21, diabetes at the age of 23, and retinopathy at the age of 25. At the age of 33, she had genetic diagnosis at the same time with her sisters.…”

Section: Literature Reviewmentioning

confidence: 99%

A novel ceruloplasmin mutation identified in a Chinese patient and clinical spectrum of aceruloplasminemia patients

Wang

et al. 2021

Metab Brain Dis

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Background and Purpose: Aceruloplasminemia (ACP) is a rare disorder of iron overload resulting from ceruloplasmin (CP) variants. Because of its rarity and heterogeneity, the diagnosis of ACP is often missed or misdiagnosed. Here, we aim to present a clinical spectrum of ACP and raise more attention to the early diagnosis.Methods: Whole exome sequencing (WES) was performed in a Chinese female patient suspected with ACP and her clinical data were collected in detail. The PubMed databases was searched for published ACP patients within the last decade, and we present a systematic review of their clinical features with data extracted from these researches.Results: A novel pathogenic variant (c.2689delC) and a known pathogenic variant (c.606dupA) within ceruloplasmin gene were identi ed in our patient and con rmed the diagnosis of ACP. Then we reviewed 50 ACP patients including the case we reported here. A possible timeline of symptoms was discovered, anemia appears rst (29.7 years old on average), followed by diabetes (37.3 years old) and nally neurological symptoms (52.2 years old). The delay in diagnosis was signi cantly shortened in patients without neurological symptoms. Biochemical triad including anemia, low to undetectable serum ceruloplasmin, low serum iron and/or hyperferritinemia, showed better sensitivity in diagnosis than clinical triad including diabetes, neurological symptoms and retinal degeneration.Conclusions: Due to the variable symptom spectrum, patients with ACP often visit different departments, which can lead to misdiagnosis. Clinical attention needs to be paid to symptoms and tests that have a warning effect. Prompt diagnosis in the early stage of the disease can be bene cial.

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Aceruloplasminaemia: A Family with a Novel Mutation and Long-Term Therapy with Deferasirox

Cited by 11 publications

References 26 publications

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

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

Deferasirox Might Be Effective for Microcytic Anemia and Neurological Symptoms Associated with Aceruloplasminemia: A Case Report and Review of the Literature

A novel ceruloplasmin mutation identified in a Chinese patient and clinical spectrum of aceruloplasminemia patients

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