New view of aceruloplasminemia: Systematic review and meta-analysis tracking dots from onset to disease development and iron-related features

Background and purpose

Aceruloplasminemia is an uncommon genetic disorder with considerable diversity in clinical manifestations and tissue iron overload, whose underlying mechanisms are unclear. We aim to explain early and follow-up clinical/biological signs, suggesting novel theories about these manifestations and brain iron uptake.

Methods

This systematic review and meta-analysis adhered to the 2020 PRISMA guidelines. PubMed and Europe PMC databases, with Web searches (Google Scholar, Science Direct), were investigated using mesh terms and keywords to identify case reports with no limit for publication date. Screening for eligibility was made by two investigators.

Results

Overall, 110 cases were included. During the disease’s initial phase, male, consanguinity and ferritin level≥ 700 ng/ml were linked to increased diabetes risk (adjusted odds ratio (aOR)= 3.6 [95% CI= 1–12.2], aOR= 6 [95% CI= 1–35.4], aOR= 12.32 [95% CI= 1.8–82.4] respectively) and female (aOR=6.5 [95% CI=1.7–23.8]) and ferritin < 700 ng/ml (aOR=5.7 [95% CI=1.7–19]) were associated with higher risk of anemia. While consanguinity was negatively correlated with neuropsychiatric symptoms in the initial phase, it was positively associated with them in follow-up. Although initial systemic signs were linked to elevated neuropsychiatric and brain iron overload risks, starting with neuropsychiatric symptoms showed an inverse association with systemic signs onset and brain iron uptake. Onset of the disease by diabetes, diabetes in follow-up, and homozygosity were the common risk factors for thalamus, basal ganglia, and dentate nuclei iron overload.

Conclusion

Despite the intricate physiopathological mechanism of aceruloplasminemia involving various factors, our systematic reviews help comprehend the clinical signs range and illustrate the disease course. Additional studies are required to delve deeper into these identified connections.