Advanced searches left 3/3

Aceruloplasminemia - DOAJ

Summarized by Plex Scholar
Last Updated: 15 September 2022

* If you want to update the article please login/register

BRAIN IRON ACCUMULATION: DON’T FORGET ACERULOPLASMINEMIA

Aceruloplasminemia is a rare autosomal recessive disease that affects iron metabolism and iron metabolism, with normal onset in adulthood. A 52-year-old man who underwent MR imaging to further define an AP diagnosis that revealed typical iron deposition and unusual T2-weighted/FLAIR hypointensities in the subcortical white matter U fibers, indicating that brain iron accumulation may be more extensive than previously expected.

Source link: https://doi.org/10.3269/1970-5492.2020.15.26


Aceruloplasminemia: Waiting for an Efficient Therapy

Aceruloplasminemia is an extremely rare hereditary disorder characterized by inadequate production of ceruloplasmin. Ceruloplasmin is a ferric iron ferroxidase that plays a key role in iron homeostasis by oxidation and mobilization of iron from stores, as well as subsequent incorporation of ferric iron into transferrin, which is also available for cell uptake via the Tf receptor. In addition, ceruloplasmin has antioxidant properties, preventing the production of deleterious reactive oxygen species by the Fenton reaction. Several phenotypes can be more heterogeneous than previously thought, with a wide range of conditions. The common therapeutic strategy is based on iron chelators that are effective in reducing systemic iron overload. The mechanisms responsible for clinical manifestation and onset of diabetes, as well as the efficacy of iron chelation therapy remain unclear. Recent animal studies in aceruloplasminemia models have fueled the possibility of new therapeutic approaches by parenteral ceruloplasmin administration.

Source link: https://doi.org/10.3389/fnins.2018.00903


A New Pathogenic Missense Variant in a Consanguineous North-African Family Responsible for a Highly Variable Aceruloplasminemia Phenotype: A Case-Report

Aceruloplasminemia is a rare autosomal recessive genetic disorder. Mutations in the ceruloplasmin gene resulted in decreased ferroxide production, which contributed to iron accumulation. Aceruloplasminemia is characterized by elevated serum ferritin levels but low transferrin saturation, resulting in cerebral, liver, and systemic iron overload. In a consanguineous North-African family, four new cases of aceruloplasminemia have been reported here. In exon 4 of the ceruloplasmin gene, which had been described earlier as of u201d unknown significance, but not connected with ACP in the HGMD database, a homozygous missense variant c. 656T> A was identified as of "unknown significance" in the dbSNP database and never associated with ACP. The proband started deferoxamine therapy when he was still symptomatic, and he quickly declined. In the asymptomatic cases, the drug was accompanied by poor tolerance and was stopped due to anemia necrequiring red blood cell transfusion, requiring anemia in the asymptomatic cases. Our collection illustrates the need for new therapeutic approaches to aceruloplasminemia.

Source link: https://doi.org/10.3389/fnins.2022.906360


Aceruloplasminemia: A Severe Neurodegenerative Disorder Deserving an Early Diagnosis

Aceruloplasminemia is a rare, adult-onset, autosomal recessive disorder characterized by systemic iron overload due to mutations in the Ceruloplasmin gene, which can lead to a lack or significant decrease in CP activity. CP is a ferroxidase that plays a significant role in iron export from various cells, particularly in the brain, where it maintains the proper iron homeostasis with neuroprotective properties. ACP is one of systemic iron overload syndromes, e. g. , many forms of genetic hemochromatosis, due to brain iron accumulation.

Source link: https://doi.org/10.3389/fnins.2019.00325


Molecular and pathological basis of aceruloplasminemia

Aceruloplasminemia is a autosomal recessive neurodegenerative disorder associated with iron accumulation in the brain and visceral organs. Patients with aceruloplasminemia patients' brains have a higher iron concentration, which is related to increased lipid peroxidation. In addition, deformed astrocytes and globular structures have demonstrated a strong response to anti-4-hydroxynononenal antibody, suggesting that elevated oxidative stress is involved in neuronal cell death in aceruloplasminemia brain. We investigated the biosynthesis of two missense ceruloplasmin proteins that result from a Japanese P177R mutation and a Dutch G631R mutation, using a Chinese hamster ovary cell expression system. The G631R mutant protein, which is predicted to change the interactions at a single type I copper-binding site, prevented copper incorporation into apoceruloplasmin, resulting in the extraction and secretion only of apoceruloplasmin. The discovery of mutant ceruloplasmin bacteria, synthesis, trafficking, and function of ceruloplasmin revealed new insight into aceruloplasminemia's molecular pathogenesis, as well as biosynthesis, trafficking, and function of ceruloplasmin.

Source link: https://doaj.org/article/ba56ed1bc4c449ed8b7feba04e1e7fe1


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

The effects of iron chelation on neurological outcomes have only been demonstrated in case studies, and they are inconsistent. Patients initiating therapy were compared to patients with neurologically symptomatic and patients without neurological signs, respectively. Results Aceruloplasminemia therapy has been tested in 48 patients around the world, including our three patients. Although some patients with neurological disorders in 11/20 were stable or improved during therapy, they were not admitted or improved during therapy, these patients were much shorter than patients who deteriorated neurologically, according to researchers who deteriorated neurologically. Conclusions: Early beginning of iron chelation therapy may delay the onset of cutaneous manifestations of aceruloplasminemia. In our review, we recommend iron chelation therapy for aceruloplasminemia patients with symptomatic anemia in combination with phlebotomy.

Source link: https://doi.org/10.1186/s13023-020-01385-w


Genetic and Clinical Heterogeneity in Thirteen New Cases with Aceruloplasminemia. Atypical Anemia as a Clue for an Early Diagnosis

Aceruloplasminemia, diabetes, retinopathy, liver disease, liver disease, and progressive neurological signs due to iron accumulation in pancreas, retina, and brain. The disease is caused by mutations in the Ceruloplasmin gene that result in a significant decrease or absence of ceruloplastin ferroxidase production, which leads to an impairment of iron metabolism. Most patients identified so far are from Japan, Japan. Prost diagnosis and therapy are often irreversible, and they can often be used to prevent neurological disorders. Here, we introduce the first collection of non-Japanese patients with aceruloplasminemia published so far, including 13 individuals from 11 families carrying 13 mutations in the CP gene, 10 of which are novel. Uncomplained anemia with low transferrin saturation and high ferritin levels without inflammation, as well as inflammation, should raise the possibility of aceruloplasminemia, which can be easily established by low serum ceruloplasmin levels.

Source link: https://doi.org/10.3390/ijms21072374


MR imaging for the quantitative assessment of brain iron in aceruloplasminemia: A postmortem validation study

Aims: Brain iron supplementation therapy can be of significant assistance in neurodegeneration with brain iron accumulation, as a biomarker for disease progression and diagnosis of iron chelation therapy. Although magnetic resonance imaging provides several quantitative measures of brain iron content, none of which have been validated for patients with a significant elevated cerebral iron burden. Sample R2* values of the aceruloplasminemia brain were compared to postmortem in situ MRI results obtained from the same subject at 3 T u2013 in situ R2*. In situ R2* at 3 T and sample R2* at 1. 5 T were highly correlated, with gray matter samples of the aceruloplasminemia subject with an iron concentration above 1000 mg/kg, 91% of change in R2*, explaining iron.

Source link: https://doi.org/10.1016/j.neuroimage.2021.118752


Quantification of different iron forms in the aceruloplasminemia brain to explore iron-related neurodegeneration

Methods: The inhomogeneous transverse relaxation rate and magnetic susceptibility obtained from 7 T MRI were combined with Electron Paramagnetic Resonance and Quantum Interference Device magnetometry, which was combined with Electron Paramagnetic Resonance and Superconducting Quantum Interference Device magnetometry. In this research, the brain iron pool in aceruloplasminemia was found to contain EPR-detectable Fe3+ ions, magnetic Fe3+ embedded in the core of ferritin and hemosiderin, and magnetic Fe3+ embedded in oxidized magnetite/maghemite minerals. Although deep gray matter structures were three times higher in ferrihydrite-iron than the temporal cortex, ferrihydrite-iron was six times more prevalent in the patient's temporal cortex than the normal situation. The temporal cortex in aceruloplasminemia had Fe3+ ions and maghemite-iron levels that were within the normal range of those in the control group. Iron-related neurodegeneration in aceruloplasminemia is mainly due to an increase in ferrihydrite-iron, with ferrihydrite-iron being the primary determinant of iron-sensitive MRI comparison.

Source link: https://doi.org/10.1016/j.nicl.2021.102657


Ceruloplasmin replacement therapy ameliorates neurological symptoms in a preclinical model of aceruloplasminemia

We investigated the possibility of ceruloplasmin replacement therapy in reducing the neuropathology in the ceruloplasmin-u2010knockout mouse model of aceruloplasminemia. Human ceruloplasmin mice were intraperitoneal administered for two months with human ceruloplasmin, which was able to enter the brain and stimulate ferroxidase activity. In particular in the choroid plexus, Ceruloplasminu2010treated mice showed improvements in motor coordination that was attributed to reduced loss of Purkinje neurons and reduced brain iron deposition, in particular in the choroid plexus. These results show that enzyme replacement therapy may be a promising treatment for aceruloplasminemia.

Source link: https://doi.org/10.15252/emmm.201708361

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions