Aceruloplasminaemia: a rare but important cause of iron overload

Doyle, Adam; Rusli, Ferry; Bhathal, Prithi S.

doi:10.1136/bcr-2014-207541

Cited by 22 publications

(16 citation statements)

References 16 publications

(12 reference statements)

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“…When the patient is without significant neurological symptomatology, ideally when they are asymptomatic, an early start to chelatase treatment is considered to be a basic factor for its success [17,26]. In accordance with the literature data, we recorded a reduction in the concentration of serum ferritin.…”

Section: Discussionsupporting

confidence: 80%

New mutation of the ceruloplasmin gene in the case of a neurologically asymptomatic patient with microcytic anaemia, obesity and supposed Wilson’s disease

Ondrejkovičová

Dražilová²,

Drakulová

et al. 2020

BMC Gastroenterol

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Background: Aceruloplasminaemia is a very rare autosomal recessive disorder caused by a mutation in the ceruloplasmin gene, which is clinically manifested by damage to the nervous system and retinal degeneration. This classical clinical picture can be preceded by diabetes mellitus and microcytic anaemia, which are considered to be early manifestations of aceruloplasminaemia. Case presentation: In our report, we describe the case of a patient with aceruloplasminaemia detected in an early stage (without clinical symptoms of damage to the nervous system) during the search for the cause of hepatopathy with very low values of serum ceruloplasmin. Molecular genetic examination of the CP gene for ceruloplasmin identified a new variant c.1664G > A (p.Gly555Glu) in the homozygous state, which has not been published in the literature or population frequency databases to date. Throughout the 21-month duration of chelatase treatment, the patient, who is 43 years old, continues to be without neurological and psychiatric symptomatology. We observed a decrease in the serum concentration of ferritin without a reduction in iron deposits in the brain on magnetic resonance imaging. Conclusion: Currently, there is no unequivocal recommendation of an effective treatment for aceruloplasminaemia. Early diagnosis is important in the neurologically asymptomatic stage.

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Section: Discussionsupporting

confidence: 80%

New mutation of the ceruloplasmin gene in the case of a neurologically asymptomatic patient with microcytic anaemia, obesity and supposed Wilson’s disease

Ondrejkovičová

Dražilová²,

Drakulová

et al. 2020

BMC Gastroenterol

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“…This estimation has obvious regional limitations, and cannot be applied in non-Japanese population, where ACP prevalence is actually unknown. Few more than one hundred of patients have been described in the literature so far, with a worldwide geographical distribution (Miyajima and Hosoi, 1993–2018; Kono, 2013; Doyle et al, 2015; Vroegindeweij et al, 2015; Pelucchi et al, 2018; Riboldi et al, 2018; Yamamura et al, 2018). While Japanese patients with neurological involvement still represent the majority (Miyajima and Hosoi, 1993–2018) the second group is represented by Italian patients reported by some referral centers for disorders of iron metabolism (Pelucchi et al, 2018).…”

Section: Epidemiologymentioning

confidence: 99%

Aceruloplasminemia: A Severe Neurodegenerative Disorder Deserving an Early Diagnosis

et al. 2019

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Aceruloplasminemia (ACP) is a rare, adult-onset, autosomal recessive disorder, characterized by systemic iron overload due to mutations in the Ceruloplasmin gene ( CP ), which in turn lead to absence or strong reduction of CP activity. CP is a ferroxidase that plays a key role in iron export from various cells, especially in the brain, where it maintains the appropriate iron homeostasis with neuroprotective effects. Brain iron accumulation makes ACP unique among systemic iron overload syndromes, e.g., various types of genetic hemochromatosis. The main clinical features of fully expressed ACP include diabetes, retinopathy, liver disease, and progressive neurological symptoms reflecting iron deposition in target organs. However, biochemical signs of the disease, namely a mild anemia mimicking iron deficiency anemia because of microcytosis and low transferrin saturation, but with “paradoxical” hyperferritinemia, usually precedes the onset of clinical symptoms of many years and sometimes decades. Prompt diagnosis and therapy are crucial to prevent neurological complications of the disease, as they are usually irreversible once established. In this mini-review we discuss some major issues about this rare disorder, pointing out the early clues to the right diagnosis, instrumental to reduce significant disability burden of affected patients.

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“…This early identification of aceruloplasminemia subjects enabled the exploration of effect of chelation therapy in the pre-neuro-symptomatic phase. Importantly, studies reported that these still asymptomatic individuals remained free of neurologic symptoms during follow-up lasting up to 10 years [44,46,58,59,[61][62][63][64]. Lifelong iron chelation therapy may thus potentially prevent neurologic symptoms.…”

Section: Aceruloplasminemiamentioning

confidence: 99%

Iron chelation in the treatment of neurodegenerative diseases

Dušek

Schneider

Aaseth

2016

Journal of Trace Elements in Medicine and Biology

104

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a b s t r a c tDisturbance of cerebral iron regulation is almost universal in neurodegenerative disorders. There is a growing body of evidence that increased iron deposits may contribute to degenerative changes. Thus, the effect of iron chelation therapy has been investigated in many neurological disorders including rare genetic syndromes with neurodegeneration with brain iron accumulation as well as common sporadic disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. This review summarizes recent advances in understanding the role of iron in the etiology of neurodegeneration. Outcomes of studies investigating the effect of iron chelation therapy in neurodegenerative disorders are systematically presented in tables. Iron chelators, particularly the blood brain barrier-crossing compound deferiprone, are capable of decreasing cerebral iron in areas with abnormally high concentrations as documented by MRI. Yet, currently, there is no compelling evidence of the clinical effect of iron removal therapy on any neurological disorder. However, several studies indicate that it may prevent or slow down disease progression of several disorders such as aceruloplasminemia, pantothenate kinase-associated neurodegeneration or Parkinson's disease.

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Aceruloplasminaemia: a rare but important cause of iron overload

Cited by 22 publications

References 16 publications

New mutation of the ceruloplasmin gene in the case of a neurologically asymptomatic patient with microcytic anaemia, obesity and supposed Wilson’s disease

New mutation of the ceruloplasmin gene in the case of a neurologically asymptomatic patient with microcytic anaemia, obesity and supposed Wilson’s disease

Aceruloplasminemia: A Severe Neurodegenerative Disorder Deserving an Early Diagnosis

Iron chelation in the treatment of neurodegenerative diseases

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