The evaluation of hyperferritinemia: An updated strategy based on advances in detecting genetic abnormalities

被引:48
作者
Aguilar-Martinez, P
Schved, JF
Brissot, P
机构
[1] Montpellier Univ Hosp, Hematol Lab, F-34295 Montpellier, France
[2] Univ Hosp Pontchaillou, Serv Malad Foie, F-35033 Rennes, France
[3] Univ Hosp Pontchaillou, INSERM, U522, F-35033 Rennes, France
关键词
D O I
10.1111/j.1572-0241.2005.40998.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The number of new genes implicated in iron metabolism has dramatically increased during the last few years. Alterations of these genes may cause hyperferritinemia associated or not with iron overload. Correct assignment of the specific disorder of iron metabolism requires the identification of the causative gene mutation. Here, we propose a rational strategy that allows targeting the gene(s) to be screened for a diagnostic purpose. This strategy relies on the age of onset of the disease, the type of clinical symptoms, the biochemical profile (elevated or normal serum transferrin saturation (TfSat)), the presence or not of visceral iron excess, and the mode of inheritance (autosomal recessive or dominant). Then, two main entities can be differentiated: genetic (adult or juvenile) hemochromatosis characterized by elevated TfSat, and hereditary hyperferritinemias where TfSat is normal (or only slightly modified). Adult genetic hemochromatosis (GH) is related mainly to mutations of the HFE gene, and exceptionally to mutations of the TFR2 gene. Juvenile GH is a rare condition related principally to mutations of the HJV gene coding for hemojuvelin, and rarely to mutations of the HAMP gene coding for hepcidin. Hereditary hyperferritinemias are linked to mutations of three genes: the L-ferritin gene responsible for the hereditary hyperferritinemia cataract syndrome (without iron overload), the ferroportin gene leading to a dominant form of iron overload, and the ceruloplasmin (CP) gene corresponding to an iron overload syndrome with neurological symptoms. The proposed strategic approach may change with the identification of other genes involved in iron metabolism.
引用
收藏
页码:1185 / 1194
页数:10
相关论文
共 87 条
  • [1] EASL International Consensus Conference on Haemochromatosis - Part II. Expert document
    Adams, P
    Brissot, P
    Powell, L
    [J]. JOURNAL OF HEPATOLOGY, 2000, 33 (03) : 487 - 496
  • [2] Variable phenotypic presentation of iron overload in H63D homozygotes: are genetic modifiers the cause?
    Aguilar-Martinez, P
    Bismuth, M
    Picot, MC
    Thelcide, C
    Pageaux, GP
    Blanc, F
    Blanc, P
    Schved, JF
    Larrey, D
    [J]. GUT, 2001, 48 (06) : 836 - 842
  • [3] Transferrin receptor-2 gene and non-C282Y homozygous patients with hemochromatosis
    Aguilar-Martinez, P
    Esculié-Coste, C
    Bismuth, M
    Giansily-Blaizot, M
    Larrey, D
    Schved, JF
    [J]. BLOOD CELLS MOLECULES AND DISEASES, 2001, 27 (01) : 290 - 293
  • [4] AguilarMartinez P, 1996, BLOOD, V88, P1895
  • [5] Transferrin receptor-2 (TFR2) mutation Y250X in Alabama Caucasian and African American subjects with and without primary iron overload
    Barton, EH
    West, PA
    Rivers, CA
    Barton, JC
    Acton, RG
    [J]. BLOOD CELLS MOLECULES AND DISEASES, 2001, 27 (01) : 279 - 284
  • [6] Genotypic and phenotypic heterogeneity of African Americans with primary iron overload
    Barton, JC
    Acton, RT
    Rivers, CA
    Bertoli, LF
    Gelbart, T
    West, C
    Beutler, E
    [J]. BLOOD CELLS MOLECULES AND DISEASES, 2003, 31 (03) : 310 - 319
  • [7] VALUE OF HEPATIC IRON MEASUREMENTS IN EARLY HEMOCHROMATOSIS AND DETERMINATION OF THE CRITICAL IRON LEVEL ASSOCIATED WITH FIBROSIS
    BASSETT, ML
    HALLIDAY, JW
    POWELL, LW
    [J]. HEPATOLOGY, 1986, 6 (01) : 24 - 29
  • [8] Noninvasive prediction of cirrhosis in C282Y-linked hemochromatosis
    Beaton, M
    Guyader, D
    Deugnier, Y
    Moirand, R
    Chakrabarti, S
    Adams, P
    [J]. HEPATOLOGY, 2002, 36 (03) : 673 - 678
  • [9] MUTATION IN THE IRON-RESPONSIVE ELEMENT OF THE L-FERRITIN MESSENGER-RNA IN A FAMILY WITH DOMINANT HYPERFERRITINEMIA AND CATARACT
    BEAUMONT, C
    LENEUVE, P
    DEVAUX, I
    SCOAZEC, JY
    BERTHIER, M
    LOISEAU, MN
    GRANDCHAMP, B
    BONNEAU, D
    [J]. NATURE GENETICS, 1995, 11 (04) : 444 - 446
  • [10] The HFE Cys282Tyr mutation as a necessary but not sufficient cause of clinical hereditary hemochromatosis
    Beutler, E
    [J]. BLOOD, 2003, 101 (09) : 3347 - 3350