Hyperferritinemia-Cataract Syndrome

Clinical Characteristics
Ocular Features: 

Lens opacification is the only ocular sign of this disorder.  These may be congenital and nuclear in location but this is variable.  Pulverulent and ‘sunflower’ light-diffracting opacities have also been described and are likely responsible for the glare that many patients experience.  In some patients cataracts may not be diagnosed until adult life.  Ferritin levels in surgically removed lenses are 1,500 times higher than controls and histochemical studies demonstrate that the crystalline lens opacities consist of intracellular L-ferritin.

Systemic Features: 

Serum levels of iron and transferrin saturation are normal but ferritin levels are high.  Most patients are asymptomatic but blood loss may lead to iron deficiency anemia.

Genetics

This is an autosomal dominant disorder resulting from mutations in the FTL gene located at 19q33.33.  Phenotypic variability is common as expressed by serum ferritin levels and the characteristics of the lens opacities.

A patient with homozygosity of the FTL mutation has been reported but the phenotype resembled that of heterozygous patients.

Cataracts may also be present among other disorders of iron metabolism.  For example, mutations in the gene HFE (6p21.3) that is responsible for a form of hemachromotosis (235200), can also be associated with lens opacities consisting of both general nuclear sclerosis and discrete opacities.  Epilepsy may be part of the phenotype as well. 

Treatment
Treatment Options: 

No systemic treatment is necessary in most patients but cataracts can be removed if visually significant.

References
Article Title: 

References

Perruccio K, Arcioni F, Cerri C, La Starza R, Romanelli D, Capolsini I, Caniglia M. The hereditary hyperferritinemia-cataract syndrome in 2 italian families. Case Rep Pediatr. 2013:806034.. Epub 2013 Dec 4.

PubMedID: 24368960

Luscieti S, Tolle G, Aranda J, Campos CB, Risse F, Mor?degn E, Muckenthaler MU, S?degnchez M. Novel mutations in the ferritin-L iron-responsive element that only mildly impair IRP binding cause hereditary hyperferritinaemia cataract syndrome. Orphanet J Rare Dis. 2013 Feb 19;8(1):30. [Epub ahead of print]

PubMedID: 23421845

Giansily-Blaizot M, Cunat S, Moulis G, Schved JF, Aguilar-Martinez P. Homozygous mutation of the 5'UTR region of the L-Ferritin gene in the hereditary hyperferritinemia-cataract syndrome and its impact on the phenotype. Haematologica. 2013 Apr;98(4):e42-3

PubMedID: 23300176

Nonnenmacher L, Langer T, Blessing H, Gabriel H, Buchwald HJ, Meneksedag C, Kohne E, Gencik M, Debatin KM, Cario H. Hereditary hyperferritinemia cataract syndrome: clinical, genetic, and laboratory findings in 5 families. Klin Padiatr. 2011 Nov;223(6):346-51.

PubMedID: 22020773

Brooks DG, Manova-Todorova K, Farmer J, Lobmayr L, Wilson RB, Eagle RC Jr, St Pierre TG, Stambolian D. Ferritin crystal cataracts in hereditary hyperferritinemia cataract syndrome. Invest Ophthalmol Vis Sci. 2002 Apr;43(4):1121-6.

PubMedID: 11923255

Girelli D, Bozzini C, Zecchina G, Tinazzi E, Bosio S, Piperno A, Ramenghi U, Peters J, Levi S, Camaschella C, Corrocher R. Clinical, biochemical and molecular findings in a series of families with hereditary hyperferritinaemia-cataract syndrome. Br J Haematol. 2001 Nov;115(2):334-40.

PubMedID: 11703332