FERROPORTIN DISEASE: A CASE SERIES AT THE REGIONAL REFERRAL CENTER FOR IRON DISORDERS IN VERONA.
(Abstract release date: 05/19/16)
EHA Library. Girelli D. 06/09/16; 133028; E1479
Prof. Domenico Girelli
Contributions
Contributions
Abstract
Abstract: E1479
Type: Eposter Presentation
Background
Ferroportin Disease (FD), due to mutations in the SLC40A1 gene encoding for the hepcidin receptor and cell membrane iron exporter ferroportin, is deemed as the most frequent form of “atypical” or “non-HFE” Hereditary Hemochromatosis (HH) (Wallace DF, Genet Med 2015). To date, knowledge on FD is mainly based on individual case reports, with heterogeneous clinical and biochemical features.
Aims
the aim of the work is to describe our experience as Regional Referral Center for Iron Disorders, after the recent implementation of a next generation sequencing (NGS)-based 2nd level genetic test for the molecular diagnosis of non-HFE HH.
Methods
we used our recently validated molecular test (Badar S, Am J Hematol 2016) combining capture and enrichment of the five HH genes (HFE, HFE2, TFR2, SLC40A1/ferroportin, and HAMP/hepcidin) through HaloPlexTM Technology and NGS using the IlluminaHiSeq 1000 platform (Illumina, San Diego CA).
Results
new cases of FD have been detected, so that we are now following 9 FD patients from 7 families. The 3bp-deletion p.Val162del, the most frequent FD-associated variant reported in literature was found in 3 families. We recently detected a new variant (p.Leu233Gln) in a patient showing mixed biochemical/pathological features between Type 4A/4B HH, i.e. marked hyperferritinemia (6,923 ng/ml), elevated transferrin saturation (85% at diagnosis), iron deposition in both liver and spleen at MRI, and iron overload in both Kupffer cells and hepatocytes at liver biopsy. Noteworthy, the mutation affected the same residue involving a different mutation (p.Leu233Pro) previously described in a patient with a quite similar phenotype (Girelli D, J Hepatol 2008). All 4 patients with p.Val162del (all females, age range 30-69) had marked hyperferritinemia (range 1,101-3,020 ug/L) and normal transferrin saturation. Despite in some cases hyperferritinemia dated back several years without treatment before the correct diagnosis, all patients were clinically asymptomatic, with no overt biochemical signs of liver disease. Hepcidin levels in FD patients were high-normal at diagnosis, but tended to decrease with iron depletion through phlebotomies.
Conclusion
our single center experience confirm FD disease as the most frequent atypical HH, and call for multicentre registries to better define the clinical features of this heterogeneous condition.
Session topic: E-poster
Keyword(s): Hemochromatosis, Iron overload
Type: Eposter Presentation
Background
Ferroportin Disease (FD), due to mutations in the SLC40A1 gene encoding for the hepcidin receptor and cell membrane iron exporter ferroportin, is deemed as the most frequent form of “atypical” or “non-HFE” Hereditary Hemochromatosis (HH) (Wallace DF, Genet Med 2015). To date, knowledge on FD is mainly based on individual case reports, with heterogeneous clinical and biochemical features.
Aims
the aim of the work is to describe our experience as Regional Referral Center for Iron Disorders, after the recent implementation of a next generation sequencing (NGS)-based 2nd level genetic test for the molecular diagnosis of non-HFE HH.
Methods
we used our recently validated molecular test (Badar S, Am J Hematol 2016) combining capture and enrichment of the five HH genes (HFE, HFE2, TFR2, SLC40A1/ferroportin, and HAMP/hepcidin) through HaloPlexTM Technology and NGS using the IlluminaHiSeq 1000 platform (Illumina, San Diego CA).
Results
new cases of FD have been detected, so that we are now following 9 FD patients from 7 families. The 3bp-deletion p.Val162del, the most frequent FD-associated variant reported in literature was found in 3 families. We recently detected a new variant (p.Leu233Gln) in a patient showing mixed biochemical/pathological features between Type 4A/4B HH, i.e. marked hyperferritinemia (6,923 ng/ml), elevated transferrin saturation (85% at diagnosis), iron deposition in both liver and spleen at MRI, and iron overload in both Kupffer cells and hepatocytes at liver biopsy. Noteworthy, the mutation affected the same residue involving a different mutation (p.Leu233Pro) previously described in a patient with a quite similar phenotype (Girelli D, J Hepatol 2008). All 4 patients with p.Val162del (all females, age range 30-69) had marked hyperferritinemia (range 1,101-3,020 ug/L) and normal transferrin saturation. Despite in some cases hyperferritinemia dated back several years without treatment before the correct diagnosis, all patients were clinically asymptomatic, with no overt biochemical signs of liver disease. Hepcidin levels in FD patients were high-normal at diagnosis, but tended to decrease with iron depletion through phlebotomies.
Conclusion
our single center experience confirm FD disease as the most frequent atypical HH, and call for multicentre registries to better define the clinical features of this heterogeneous condition.
Session topic: E-poster
Keyword(s): Hemochromatosis, Iron overload
Abstract: E1479
Type: Eposter Presentation
Background
Ferroportin Disease (FD), due to mutations in the SLC40A1 gene encoding for the hepcidin receptor and cell membrane iron exporter ferroportin, is deemed as the most frequent form of “atypical” or “non-HFE” Hereditary Hemochromatosis (HH) (Wallace DF, Genet Med 2015). To date, knowledge on FD is mainly based on individual case reports, with heterogeneous clinical and biochemical features.
Aims
the aim of the work is to describe our experience as Regional Referral Center for Iron Disorders, after the recent implementation of a next generation sequencing (NGS)-based 2nd level genetic test for the molecular diagnosis of non-HFE HH.
Methods
we used our recently validated molecular test (Badar S, Am J Hematol 2016) combining capture and enrichment of the five HH genes (HFE, HFE2, TFR2, SLC40A1/ferroportin, and HAMP/hepcidin) through HaloPlexTM Technology and NGS using the IlluminaHiSeq 1000 platform (Illumina, San Diego CA).
Results
new cases of FD have been detected, so that we are now following 9 FD patients from 7 families. The 3bp-deletion p.Val162del, the most frequent FD-associated variant reported in literature was found in 3 families. We recently detected a new variant (p.Leu233Gln) in a patient showing mixed biochemical/pathological features between Type 4A/4B HH, i.e. marked hyperferritinemia (6,923 ng/ml), elevated transferrin saturation (85% at diagnosis), iron deposition in both liver and spleen at MRI, and iron overload in both Kupffer cells and hepatocytes at liver biopsy. Noteworthy, the mutation affected the same residue involving a different mutation (p.Leu233Pro) previously described in a patient with a quite similar phenotype (Girelli D, J Hepatol 2008). All 4 patients with p.Val162del (all females, age range 30-69) had marked hyperferritinemia (range 1,101-3,020 ug/L) and normal transferrin saturation. Despite in some cases hyperferritinemia dated back several years without treatment before the correct diagnosis, all patients were clinically asymptomatic, with no overt biochemical signs of liver disease. Hepcidin levels in FD patients were high-normal at diagnosis, but tended to decrease with iron depletion through phlebotomies.
Conclusion
our single center experience confirm FD disease as the most frequent atypical HH, and call for multicentre registries to better define the clinical features of this heterogeneous condition.
Session topic: E-poster
Keyword(s): Hemochromatosis, Iron overload
Type: Eposter Presentation
Background
Ferroportin Disease (FD), due to mutations in the SLC40A1 gene encoding for the hepcidin receptor and cell membrane iron exporter ferroportin, is deemed as the most frequent form of “atypical” or “non-HFE” Hereditary Hemochromatosis (HH) (Wallace DF, Genet Med 2015). To date, knowledge on FD is mainly based on individual case reports, with heterogeneous clinical and biochemical features.
Aims
the aim of the work is to describe our experience as Regional Referral Center for Iron Disorders, after the recent implementation of a next generation sequencing (NGS)-based 2nd level genetic test for the molecular diagnosis of non-HFE HH.
Methods
we used our recently validated molecular test (Badar S, Am J Hematol 2016) combining capture and enrichment of the five HH genes (HFE, HFE2, TFR2, SLC40A1/ferroportin, and HAMP/hepcidin) through HaloPlexTM Technology and NGS using the IlluminaHiSeq 1000 platform (Illumina, San Diego CA).
Results
new cases of FD have been detected, so that we are now following 9 FD patients from 7 families. The 3bp-deletion p.Val162del, the most frequent FD-associated variant reported in literature was found in 3 families. We recently detected a new variant (p.Leu233Gln) in a patient showing mixed biochemical/pathological features between Type 4A/4B HH, i.e. marked hyperferritinemia (6,923 ng/ml), elevated transferrin saturation (85% at diagnosis), iron deposition in both liver and spleen at MRI, and iron overload in both Kupffer cells and hepatocytes at liver biopsy. Noteworthy, the mutation affected the same residue involving a different mutation (p.Leu233Pro) previously described in a patient with a quite similar phenotype (Girelli D, J Hepatol 2008). All 4 patients with p.Val162del (all females, age range 30-69) had marked hyperferritinemia (range 1,101-3,020 ug/L) and normal transferrin saturation. Despite in some cases hyperferritinemia dated back several years without treatment before the correct diagnosis, all patients were clinically asymptomatic, with no overt biochemical signs of liver disease. Hepcidin levels in FD patients were high-normal at diagnosis, but tended to decrease with iron depletion through phlebotomies.
Conclusion
our single center experience confirm FD disease as the most frequent atypical HH, and call for multicentre registries to better define the clinical features of this heterogeneous condition.
Session topic: E-poster
Keyword(s): Hemochromatosis, Iron overload
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