Liver and Bile
J Hepatol. 2022;76(3):568–76
A simple clinical score to promote and enhance ferroportin disease screening
Background and aims: Ferroportin disease is a rare genetic iron overload disorder which may be underdiagnosed, with recent data suggesting it occurs at a higher prevalence than suspected. Costs and the lack of defined criteria to prompt genetic testing preclude large-scale molecular screening. Hence, the authors aimed to develop a readily available scoring system to promote and enhance ferroportin disease screening.
Methods: The derivation cohort included probands tested for ferroportin disease from 2008 to 2016 in a rare disease network. Data were prospectively recorded. Univariate and multivariate logistic regression were used to determine significant criteria, and odds ratios were used to build a weighted score. A cut-off value was defined using a ROC curve with a predefined aim of 90% sensitivity. An independent cohort was used for cross validation.
Results: The derivation cohort included 1306 patients. Mean age was 55 ± 14 years, ferritin 1351 ± 1357 μg/l, and liver iron concentration (LIC) 166 ± 77 μmol/g. Pathogenic variants (n = 32) were identified in 71 patients. In multivariate analysis: female sex, younger age, higher ferritin, higher LIC and the absence of hypertension or diabetes were significantly associated with the diagnosis of ferroportin disease (AUROC in whole derivation cohort: 0.83 [0.78–0.88]). The weighted score was based on sex, age, the presence of hypertension or diabetes, ferritin level and LIC. An AUROC of 0.83 (0.77–0.88) was obtained in the derivation cohort without missing values. Using 9.5 as a cut-off, sensitivity was 93.6% (91.7–98.3%), specificity 49.5% (45.5–53.6%), positive likelihood ratio 1.8 (1.6–2.0) and negative likelihood ratio 0.17 (0.04–0.37).
Conclusion: The authors describe a readily available score with simple criteria and good diagnostic performance that could be used to screen patients for ferroportin disease in routine clinical practice.