OJBD  Vol.2 No.1 , March 2012
On the Hyperferritinemia and Hereditary Cataract Syndrome
Abstract: Introduction. Mutations in the promoter region of ferritin light gene can induce an uncontrolled over expression of this protein. Consequently, ferritin is found in serum at very high levels (~1000 ng/mL) and it accumulates in the crystalline lens, generating cataracts. This entity is known as hyperferritin and hereditary cataract syndrome (HHCS) which is inherited in an autosomal dominant manner. Case Presentation. We describe a family affected by HHCS. The proband was identified among subjects submitted to a biological screening for hemochromatosis. He had very high levels of serum ferritin (~900 ng/mL) with normal transferrin saturation (TS). The proband has a single H63D HFE-gene mutation and normal HAMP-gene. He was submitted to periodical phlebotomies that induced anemia and a decrease in TS but no changes on serum ferritin levels. Analyses of promoter region of ferritin-light chain gene showed a 39 C > T mutation, responsible for HHCS. The proband’s sister carried also this mutation. Both subjects had developed cataracts. Discussion. Similar to the first family described carrying this syndrome and to other cases reported, the proband was erroneously submitted to phlebotomies. Clinical consequences are illustrated in this report. HHCS is an infrequent entity which has to be correctly identified. The unique therapeutic approach to this syndrome must be cataract surgery.
Cite this paper: M. José Perez-Lucena, M. Sierra Moreno-Rosel, M. Sagarra-Tió and J. Félez, "On the Hyperferritinemia and Hereditary Cataract Syndrome," Open Journal of Blood Diseases, Vol. 2 No. 1, 2012, pp. 11-13. doi: 10.4236/ojbd.2012.21002.

[1]   J. S. Rahi, “Childhood Blindness: A UK Epidemiological Perspective,” Eye (Lond), Vol. 21, 2007, pp. 1249-1253. doi:10.1038/sj.eye.6702837

[2]   D. Girelli, R. Corrocher, D. Bisceglia, et al., “Molecular Basis for the Recently Described Hereditary Hyperfer-ritinemia-Cataract Syndrome: A Mutation in the Iron- Responsive Element of Ferritin L-Subunit Gene (the ‘Verona Mutation’)," Blood, Vol. 86, 1995, pp. 4050- 4053.

[3]   C. Beaumont, P. Leneuve, I. Devaux, et al., “Mu-tation in the Iron Responsive Element of the L Ferritin mRNA in a Family with Dominant Hyperferritinaemia and Cataract,” Nature Genetics, Vol. 11, 1995, pp. 444-446. doi:10.1038/ng1295-444

[4]   D. Bonneau, I. Winter-Fuseau, M. N. Loiseau, et al., “Bilateral Cataract and High Serum Ferritin: A New Domi- nant Genetic Disorder?” Journal of Medical Genetics, Vol. 32, No. 10, 1995, pp. 778-779. doi:10.1136/jmg.32.10.778

[5]   V. Vanita, J. F. Hejtmancik, H. C. Hennies, et al., “Sutural Cataract Associated with a Mutation in the Ferritin Light Chain Gene (FTL) in a Family of Indian Origin,” Molecular Vision, Vol. 21, 2006, pp. 93-99.

[6]   C. Camaschella, E. Poggiali, “Towards Explaining ‘Unexplained Hyperferritinemia’,” Haematologica, Vol. 94, No. 3, 2009, pp. 307-309. doi:10.3324/haematol.2008.005405

[7]   N. Freixenet, M. S. Moreno-Rosel, M. J. Barceló, et al., “Detection of Hereditary Hemochromatosis and Biochemical Iron-Overload in Primary Care: A Multicenter Case-Finding Study in Spain,” American Journal of Hematology, Vol. 85, No. 4, 2010, pp. 294-296. doi:10.1002/ajh.21634

[8]   K. J. Hintze and E. C. Theil, “Cellular Regulation and Molecular Interactions of the Ferritins,” Cellular and Molecular Life Sciences, Vol. 63, No. 5, 2006, pp. 591- 600. doi:10.1007/s00018-005-5285-y

[9]   M. Cazzola, G. Bergamaschi, L. Tonon, et al. “Hereditary Hyperferritinemia-Cataract Syndrome: Relationship between Phenotypes and Specific Mutations in the Iron- Responsive Element of Ferritin Light-Chain mRNA,” Blood, Vol. 90, No. 2, 1997, pp. 814-821.

[10]   G. Milloning, M. U. Muckenthaler and S. Mueller, “Hyperferritinaemia-Cataract Syndrome: Worldwide Mutations and Phenotype of an Increasingly Diagnosed Genetic Disorder,” Human Genomics, Vol. 4, No. 4, 2010, pp. 250-262.

[11]   C. Kannengiesser, A. M. Jouanolle, G. Hetter, et al., “A New Missense Mutation in the L Ferritin Coding Sequence Associated with Elevated Levels of Glyscosylated Ferritin in Serum and Absence of Iron Overload,” Haematologica, Vol. 94, No. 3, 2009, pp. 335-339. doi:10.3324/haematol.2008.000125

[12]   J. A. García Erce, T. Cortés, L. Cremonesi, et al., “Hiperferritinemia Familiar y Cataratas Congenitas Aso- ciadas a Mutación del Gen HFE. Dos Nuevas Familias Espa?olas y una Nueva Mutación (A37T: ‘Zaragoza’),” Medicina Clínica (Barc), Vol. 127, No. 2, 2006, pp. 55- 58.