A simple clinical score to promote and enhance ferroportin disease screening.

BACKGROUND & 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, we aimed to develop a readily available scoring system to promote and enhance ferroportin disease screening.

METHODS

Our derivation cohort included probands tested for ferroportin disease from 2008 to 2016 in our 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

Our derivation cohort included 1,306 patients. Mean age was 55±14 years, ferritin 1,351±1,357 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

We 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.

LAY SUMMARY

Increased iron burden associated with metabolic syndrome is a very common condition. Ferroportin disease is a dominant genetic iron overload disorder whose prevalence is higher than initially thought. They can be difficult to distinguish from each other, but the limited availability of genetic testing and the lack of definitive guidelines prevent adequate screening. We herein describe a simple and definitive clinical score to help clinicians decide whether to perform genetic testing.

Informations de copyright

Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest Dr. LOUSTAUD-RATTI reports personal fees from Abbvie, personal fees from Gilead, personal fees from IPSEN, outside the submitted work. Dr. Causse reports personal fees from Abbvie, personal fees from Gilead Sciences, personal fees from MSD, outside the submitted work. Dr. SI AHMED reports grants and non-financial support from Abbvie, grants and non-financial support from Gilead, grants from MSD, outside the submitted work. Dr. Ganne-Carrié reports personal fees and non-financial support from GILEAD, personal fees and non-financial support from BAYER, personal fees from IPSEN, outside the submitted work. Dr. Loréal reports personal fees and other from Diafir, outside the submitted work. Other authors have no conflict of interest to disclose. Please refer to the accompanying ICMJE disclosure forms for further details.