Abstract
Ferritin is an acute-phase reactant that is elevated in the course of infectious, inflammatory, autoimmune, and oncological diseases and the hemophagocytic syndrome. In asymptomatic patients, isolated hyperferritinemia may be due to different causes depending on whether or not it is accompanied by iron overload. Hyperferritinemia values above 300 ng/ml and an excess of body iron levels may be indicative of hemochromatosis. However, if such values develop in the absence of iron overload, they may be secondary to hemochromatosis type 4a (ferroportin disease) or more often to hereditary hyperferritinemia–cataract syndrome (HHCS; Aguilar-Martinez et al., Am J Gastroenterol 100:1185–1194, 2005; Ferrante et al., Eur J Gastroenterol Hepatol 17:1247–1253, 2005). HHCS results from different mutations in the L-ferritin gene (FTL) on chromosome 19 (19q13.1), causing autosomal dominant transmission (Bertola et al., Curr Drug Targets Immune Endocr Metabol Disord 4:93–105, 2004). We present a child with HHCS due to the allelic variant c.-167C>T (C33T) in the iron-responsive element region of the FTL gene. When pediatricians encounter an asymptomatic patient with isolated hyperferritinemia in the absence of iron overload, they should consider the possibility of HHCS, especially if other members of the family have developed cataracts from a young age.
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References
Aguilar-Martinez P, Schved JF, Brissot P (2005) The evaluation of hyperferritinemia: an updated strategy based on advances in detecting genetic abnormalities. Am J Gastroenterol 100:1185–1194
Balas A, Aviles MJ, Garcia-Sanchez F et al (1999) Description of a new mutation in the L-ferrin iron-responsive element associated with hereditary hyperferritinemia–cataract syndrome in a Spanish family. Blood 93:4020–4021
Barton JC, Lafreniere SA, Leiendecker-Foster C et al (2009) HFE, SLC40A1, HAMP, HJV, TFR2, and FTL mutations detected by denaturing high-performance liquid chromatography after iron phenotyping and HFE C282Y and H63D genotyping in 785 HEIRS Study participants. Am J Hematol 84:710–714
Bertola F, Veneri D, Bosio S et al (2004) Hyperferritinaemia without iron overload: pathogenic and therapeutic implications. Curr Drug Targets Immune Endocr Metabol Disord 4:93–105
Cao W, McMahon M, Wang B et al (2010) A case report of spontaneous mutation (C33>U) in the iron-responsive element of L-ferritin causing hyperferritinemia–cataract syndrome. Blood Cells Mol Dis 44:22–27
Cazzola M (2005) Role of ferritin and ferroportin genes in unexplained hyperferritinaemia. Best Pract Res Clin Haematol 18:251–263
Cazzola M, Bergamaschi G, Tonon L et al (1997) Hereditary hyperferritinemia–cataract syndrome: relationship between phenotypes and specific mutations in the iron-responsive element of ferritin light-chain mRNA. Blood 90:814–821
Craig JE, Clark JB, McLeod JL et al (2003) Hereditary hyperferritinemia–cataract syndrome: prevalence, lens morphology, spectrum of mutations, and clinical presentations. Arch Ophthalmol 121:1753–1761
Ferrante M, Geubel AP, Fevery J et al (2005) Hereditary hyperferritinaemia–cataract syndrome: a challenging diagnosis for the hepatogastroenterologist. Eur J Gastroenterol Hepatol 17:1247–1253
Garcia Erce JA, Cortes T, Cremonesi L et al (2006) Hyperferritinemia–cataract syndrome associated to the HFE gene mutation. Two new Spanish families and a new mutation (A37T: “Zaragoza”). Med Clín 127:55–58
Girelli D, Bozzini C, Zecchina G et al (2001) Clinical, biochemical and molecular findings in a series of families with hereditary hyperferritinaemia–cataract syndrome. Br J Haematol 115:334–340
Gonzalez-Huerta L, Ramirez-Sanchez V, Rivera-Vega M et al (2008) A family with hereditary hyperferritinaemia cataract syndrome: evidence of incomplete penetrance and clinical heterogeneity. Br J Haematol 143:596–598
Goralska M, Holley BL, McGahan MC (2003) Identification of a mechanism by which lens epithelial cells limit accumulation of overexpressed ferritin H-chain. J Biol Chem 278:42920–42926
Kannengiesser C, Jouanolle AM, Hetet G et al (2009) A new missense mutation in the L ferritin coding sequence associated with elevated levels of glycosylated ferritin in serum and absence of iron overload. Haematologica 94:335–339
Mumford AD, Cree IA, Arnold JD et al (2000) The lens in hereditary hyperferritinaemia cataract syndrome contains crystalline deposits of L-ferritin. Br J Ophthalmol 84:697–700
Acknowledgements
The authors gratefully acknowledge the following grant sponsors: the Spanish “Fondo de Investigaciones Sanitarias” (FIS 07/0074), the “Fundación Mutua Madrileña de Investigación Biomédica” (FMM 2007-73), and the Genomics Facility for expert assistance of the “Fundación para la Investigación Biomédica del Hospital Universitario 12 de Octubre.”
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The authors declare no conflict of financial interest with the organizations that sponsored the research of this article.
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Álvarez-Coca-González, J., Moreno-Carralero, MI., Martínez-Pérez, J. et al. The hereditary hyperferritinemia–cataract syndrome: a family study. Eur J Pediatr 169, 1553–1555 (2010). https://doi.org/10.1007/s00431-010-1251-2
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DOI: https://doi.org/10.1007/s00431-010-1251-2