Генетически обусловленные нарушения обмена железа

В обзоре представлена информация о генетически обусловленных заболеваниях вследствие нарушения обмена железа, основные аспекты обмена железа в норме, рассмотрены механизмы его нарушений при каждой из описанных патологий. Обзор содержит информацию об основных клинических проявлениях, изменениях лабораторных показателей и принципах терапии.

нарушения обмена железа, гемохроматоз, IRIDA, сидеробластные анемии, ферропортин, гепсидин, атрансферринемия, ацеруллоплазминемия

1. Ganz T. Hepcidin and iron regulation, 10 years later. Blood 2011; 117: 4425-33.

2. Brissot P., et al. Current approach to hemochromatosis. Blood Rev 2008; 22: 195-210.

3. Camaschella C., Poggiali E. Inherited disorders of iron metabolism. Curr Opin Pediatr 2011; 23: 14-20.

4. Andrews N.C. Forging a field: the golden age of iron biology. Blood 2008; 112: 219-30.

5. Hentze M.W., Muckenthaler M.U., Andrews N.C. Balancing Acts: Molecular Control of Mammalian Iron Metabolism. Cell 2004; 117: 285-97.

6. De Falco L., Sanchez M., Silvestri L., Kannengiesser C., Muckenthaler M.U., Iolascon A., Gouya L., et al. C. Iron refractory iron deficiency anemia. Haematol 2013; 98 (6): 845-53.

7. Pippard M.J. Iron deficiency anemia, anemia of chronic disorders and iron overload / In Porwit A., McCullough J., Erber W.N., editors. Blood and bone marrow pathology. 2nd ed. Edinburgh: Churchill Livingstone, 2011. p. 173-95.

8. Aguilar-Martinez P., Grandchamp B., Cunat S., Cadet E., Blanc F., Nourrit M., Lassoued K., et al. Iron overload in HFE C282Y heterozygotes at first genetic testing: a strategy for identifying rare HFE variants. Haematol 2011; 96: 507-14.

9. Camaschella C. Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders. Blood 2005; 106 (12): 3710-7.

10. Lyon E., Frank E. Hereditary hemochromatosis since discovery of the HFE gene. Clin Chemistry 2001; 47 (7): 1147-56.

11. Wallace D.F., Subramanian V.N. Non-HFE haemochromatosis. World J Gastroenterol 2007; 13 (35): 4690-98.

12. Lanzara C., Roetto A., Daraio F., Rivard S., Ficarella R., Simard H., Cox T.M., et al. Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis. Blood 2004; 103 (11): 4317-21.

13. De Domenico I., McVey Ward D., Langelier C., Vaughn M.B., Nemeth E., Sundquist W.I., Ganz T., et al. The Molecular Mechanism of Hepcidin-mediated Ferroportin Down-Regulation. Mol Biol Cell 2007; 18: 2569-70.

14. Montosi G., Donovan A., Totaro A., Garuti C., Pignatti E., Cassanelli S., et al. Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J Clin Invest 2001; 108: 619-23.

15. Pietrangelo A. The ferroportin disease. Blood Cell Mol Dis 2004; 32: 131-8.

16. De Domenico I., McVey Ward D., Langelier C., Vaughn M.B., Nemeth E., Sundquist W.I., Ganz T., et al. The Molecular mechanism of hepcidin-mediated ferroportin down-regulation. Mol Biol Cell 2007; 18: 2569-78 .

17. Pietrangelo A. The ferroportin disease. Clin Liv Dis 2014; 3 (5): 98-100.

18. Kato J., Fujikawa K., Kanda M., Fukuda N., Sasaki K., Takayama T., Kobune M., et al. A mutation, in the iron-responsive element of H ferritin mRNA, causing autosomal dominant iron overload. Am J Hum Genet 2001; 69 (1): 191-7.

19. Brissot P. Current appoaches to the management of hemochromatosis. Am Soc Hematol Education Book, 2006, pp. 36-41.

20. Du X., She E., Gelbart T., Thiksa J., Lee P., Xia Y., Khovananth K., et al. The serine protease TMPRSS6 is required to sense iron deficiency. Science 2008, 320 (5879): 1088-92.

21. Folgueras A.R., de Lara F.M., PendSs A.M., Garabaya C., Rodrfguez F., Astudijlo A., Bernal T., et al. Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis. Blood 2008, 112: 2539-45.

22. Ramsay A.J., Hooper J.D., Folgueras A.R., Velasco G., Lopez-Otin C. Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis. Haematol 2009; 94: 840-9.

23. Melis M.A., Cau M., Congiu R., et al. A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron. Haematol 2008; 93: 1473-9.

24. Finberg K.E., Heeney M.M., Campagna D.R., et al. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet 2008; 40: 569-71.

25. Finberg K.E. Iron-refractory iron deficiency anemia. Semin Hematol 2009; 46 (4): 378-8.

26. Camaschella С., Poggiali E. Inherited disorders of iron metabolism. Current opinion in pediatrics 2011; 23: 14-20.

27. Camaschella С. State of the Art - How I manage patients with atypical microcytic anaemia. British Journal of Haematology 2013; 160 (1): 12-24.

28. Cau M., Galanello R., Giagu N., Melis M.A. Responsiveness to oral iron and ascorbic acid in a patient with IRIDA. Blood Cells Mol Dis 2012; 48 (2): 121-3.

29. Sasu B.J., Cooke K.S., Arvedson T.L., Plewa C., Ellison A.R., Sheng J., et al. Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia. Blood 2010; 115 (17): 3616-24.

30. Hohlbaum A.M., Trentman S., Gille H., Allersdorfer A., Belaiba R.S., Huelsmeyer M., et al. Discovery and Preclinical Characterization of a Novel Hepcidin Antagonist with Tunable PK/PD Properties for the Treatment of Anemia in Different Patient Populations. ASH Annual Meeting Abstracts 2011; 118 (21): 687.

31. Akinc A., Chan-Daniels A., Sehgal A., Foster D., Bettencourt B.R., Hettinger J., et al. Targeting the Hepcidin Pathway with RNAi Therapeutics for the Treatment of Anemia. ASH Annual Meeting Abstracts. 2011; 118 (21): 688.

32. Trombini P., Coliva T., Nemeth E., Mariani R., Ganz T., Biondi A., Piperno A. Effects of plasma transfusion on hepcidin production in human congenital hypotransferrinemia. Haematol 2007; 92 (10): 1407-10.

33. Grandchamp B., Hetet G., Kannengiesser C., Oudin C., Beaumont C., Rodrigues-Fcrreira S., et al. A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene. Blood 2011; 118: 6660-6.

34. Lolascon A., Camaschella C., Pospisilova D., Piscopo C., Tchernia G., Beaumont C. Natural history of recessive inheritance of DMTI mutations. J pediatr 2008, 152: 136-9.

35. Beaumont C., Delaunay J., Hetet G., Grandchamp B., de Montalembert M., Tchernia G. Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. Blood 2006, 107: 4168-70.

36. Fleming M.D. Congenital sideroblastic anemias: iron and heme lost in mitochondrial translation. American Society of Hematology. Hematology Education Book, 2011, pp. 525-31.

37. Camaschella C. Recent advances in the understanding of inherited sideroblastic anaemia. Br J Haematol 2008; 143 (1): 27-38.

38. Camaschella C., Campanella A., De Falco L., Boschetto L., Merlini R., Silvestri L., Levi S., et al. The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload. Blood 2007, 110 (4): 1353-8.

39. Wingert R.A., Galloway J.L., Barut B., Foott H., Fraenkel P., Axe J.L., Weber G.J., et al. Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis. Nature 2005; 436 (7053): 1035-39.

40. Iolascon A., De Falco L., Beaumont C. Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis. Haematol 2009; 94 (3): 395-408.

41. Loreal O., Turlin B., Pigeon C., Moisan A., Ropert M., Morice P., et al. Aceruloplasminemia: new clinical, pathophysiological and therapeutic insights. J Hepatol 2002; 36 (6): 85-6.

42. Nittis T., Gitlin J.D. The copper-iron connection: hereditary aceruloplasminemia. Semin Hematol 2002; 39 (4): 282-9.

43. Kono S. Aceruloplasminemia: An update. Inter Rev Neurobiol 2013; 125-51.

44. Tai M., Matsuhashi N., Ichii O., Suzuki T., Ejiri Y., Kono S., Terada T., et al. Epub 2014; 44 (12): 1253-8.

45. Miyajima H. Aceruloplasminemia. Neuropathol 2015; 35: 83-90.