Z Gastroenterol 2019; 57(05): e161
DOI: 10.1055/s-0039-1691931
POSTER
Hepatologie
Georg Thieme Verlag KG Stuttgart · New York

High pre-test likelihood for non-HFE mutations through full exome sequencing in patients with hepatic iron overload

A Viveiros
1   Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
,
B Schäfer
1   Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
,
M Höppner
2   Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
,
A Finkenstedt
1   Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
,
C Kremser
3   Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria
,
M Plaikner
3   Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria
,
B Henninger
3   Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria
,
S Franzenburg
4   Institute of Clinical Molecular Biology, University of Kiel, Kiel, Germany
,
A Franke
4   Institute of Clinical Molecular Biology, University of Kiel, Kiel, Germany
,
H Tilg
1   Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
,
H Zoller
1   Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
› Author Affiliations
Further Information

Publication History

Publication Date:
16 May 2019 (online)

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Background:

More than 80% of patients with hemochromatosis are homozygous for the p.Cys282Tyr mutation in the HFE gene. Recent studies have shown that even by comprehensive genetic testing using next generation sequencing methods, only a minority of patients with suspected non- HFE hemochromatosis harbor disease-causing mutations in HAMP, HJV, HFE, TFR2 or SLC40A1. The aim of the present study was to determine the prevalence of mutations in HFE and non-HFE hemochromatosis genes in a cohort of patients with hyperferritinemia.

Methods:

Between September 2007 and November 2017 410 patients were referred for the evaluation of high serum ferritin to our outpatient liver clinic. This retrospective analysis included the results from comprehensive clinical and biochemical workup including non-invasive assessment of parenchymal iron in liver spleen and pancreas by R2* mapping.

Results:

Forty-one (10%) patients were homozygous for the p.Cys282Tyr mutation in HFE. From all other patients, 199 had confirmed hepatic iron overload, of whom 38 patients had given their written informed consent for further genetic testing by full exome sequencing. Potentially disease-causing mutations were identified in 16 (42%) patients. When ferritin, transferrin saturation, liver and spleen R2*, plasma hepcidin concentration and CRP were included as continuous variables in a multivariable binary logistic regression analysis none were independently associated with the presence of non-HFE mutations. However, low to normal spleen iron defined as a spleen R2* < 60 s-1 was significantly associated with the presence of non-HFE mutations (OR 7.56, p = 0.009).

Conclusion:

In conclusion, our study shows that full exome sequencing has a high pre-test likelihood for the genetic diagnosis of non-HFE hemochromatosis in patients with hepatic iron overload and low to normal spleen iron concentration.