Última actualización:
November 08, 2017
Años publicados: 2009, 2012, 2017
NORD gratefully acknowledges Joshua L. Dunaief, MD, PhD, Adele Nissen Professor of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, for assistance in the preparation of this report.
Hyperferritinemia-cataract syndrome is an extremely rare genetic disorder characterized by the early onset of cataracts associated with persistently elevated levels of ferritin in the blood plasma. Ferritin is a protein that binds to iron and is used as an indicator of the body’s iron stores. Cataracts are the only known complication associated with this disorder. Hyperferritinemia-cataract syndrome is caused by mutations to ferritin light chain (FTL) gene. This mutation is inherited as an autosomal dominant trait.
The only known symptom of hyperferritinemia-cataract syndrome is the early onset of cataracts, usually between the second and fourth decades of life. However, onset of the disorder has been reported in children as young as five and adults more than 40. The overall prognosis of the disorder is very good. The severity of the hyperferritinemia-cataract syndrome can vary greatly from one person to another even among members of the same family. Some individuals with characteristic mutations of the FLT gene have not developed any symptoms (asymptomatic).
Cataracts are characterized by a clouding (opacity) of the lenses of the eye and can affect vision. The lens of an eye is the clear front portion of the eye through which light passes. The light is focused on the retina, the thin nerve-rich membrane lining the back of the eye. The retina converts light into nerve impulses and relays the information along the optic nerve to the brain. Cataracts can potentially affect both eyes and may cause several symptoms. Evidence suggests that cataracts in hyperferritinemia-cataract syndrome may become progressively worse.
Individuals with hyperferritinemia-cataract syndrome may experience glare symptoms that are worse when driving at night or in bright sunlight. Glare symptoms means that headlights, lamps, and other lights may appear too bright or have a halo form around them. Some affected individuals may be abnormally sensitive to light (photophobia) or experience blurred or hazy vision.
Hyperferritinemia-cataract syndrome is caused by mutations of the ferritin light chain (FTL) gene and is inherited as an autosomal dominant trait.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy. The risk is the same for males and females.
In some individuals, the disorder is due to a spontaneous (de novo) genetic mutation that occurs in the egg or sperm cell. In such situations, the disorder is not inherited from the parents.
Mutations of the FTL gene in hyperferritinemia-cataract syndrome affect a region of the gene known as the iron regulatory element (IRE). A specialized protein called iron regulatory protein (IRP) normally binds to the IRE and suppresses the creation of ferritin. Mutations of the IRE prevent the binding of this protein and ultimately results in elevated levels of ferritin it the blood plasma. Ferritin is also commonly found in the lenses of the eyes. In individuals with hyperferritinemia-cataract syndrome, excess amounts of ferritin have been found in the lenses of the eyes and are believed to cause the development of cataracts.
Hyperferritinemia-cataract syndrome is an extremely rare disorder that affects males and females in equal numbers. More than 100 families with the disorder have been described in the medical literature. The prevalence of hyperferritinemia-cataract syndrome has been estimated at 1 in 200,000 people in the general population. Because the disorder is so rare, it often goes unrecognized or undiagnosed, making it difficult to determine the disorder’s true frequency in the general population. Hyperferritinemia-cataract syndrome was first described in the medical literature in 1995.
A diagnosis of hyperferritinemia-cataract syndrome is made based upon identification of characteristic symptoms (e.g., cataracts), a detailed patient history, a thorough clinical evaluation and a variety of specialized tests such as blood tests, which can reveal elevated levels of ferritin in the blood plasma.
Treatment
There is no specific treatment for hyperferritinemia-cataract syndrome. Cataracts are the only known complication of the disorder. Individuals are treated with corrective glasses, contact lenses and, if vision is impaired to the point of interference with daily activities, then cataract surgery is performed. During cataract surgery, the cloudy lens inside the eye is replaced with a clear plastic lens. This surgery is technologically advanced and has a high success rate.
Therapy involving the regular removal of blood via a vein (known as a venesection or phlebotomy) is a common therapy for disorders associated with excess iron in the blood, but is not recommended as a therapy for hyperferritinemia-cataract syndrome.
Genetic counseling may be of benefit for affected individuals and their families.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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Some current clinical trials also are posted on the following page on the NORD website:
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For information about clinical trials sponsored by private sources, contact:
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For information about clinical trials conducted in Europe, contact:
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TEXTBOOKS
Rimoin D, Connor JM, Pyeritz RP, Korf BR. Eds. Emory and Rimoin’s Principles and Practice of Medical Genetics. 4th ed. New York, NY: Churchill Livingstone; 2002:2657.
JOURNAL ARTICLES
Del Castillo Rueda A, Fernandez Ruano ML. Hereditary hyperferritinemia cataracts syndrome in a Spanish family caused by the A40G mutation (Paris) in the L-ferritin (FTL) gene associated with the mutation H63D in the HFE gene. Med Clin (Barc). 2007;129:414-417.
Burdon KP, Sharma S, Chen S, et al. A novel deletion in the FTL gene causes hereditary hyperferritinemia cataract syndrome (HHCS) by alteration of the transcription start site. Hum Mutat. 2007;28:742.
Christiansen G, Mohney BG. Hereditary hyperferritinemia syndrome. J AAPOS. 2007;11:294-296.
Ismail AR, Lachlan KL, Mumford AD, Temple IK, Hodgkins PR. Hereditary hyperferritinemia cataract syndrome: ocular, genetic, and biochemical findings. Eur J Ophthalmol. 2006;16:153-160.
Lachlan KL, Temple IK, Mumford AD. Clinical features and molecular analysis of seven British kindreds with hereditary hyperferritinemia cataract syndrome. Eur J Hum Genet. 2004;12:790-796.
Craig JE, Clark JB, McLeod JL, et al. Hereditary hyperferritinemia-cataract syndrome: prevalence, lens morphology, spectrum of mutations, and clinical presentations. Arch Ophthalmol. 2003;121:1753-1761.
Ponka P. Rare causes of hereditary iron overload. Semin Hematol. 2002;39:249-262.
INTERNET
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Hyperferritinemia-Cataract Syndrome. Entry No: 600886. Last Edited:10/19/2017. Available at: https://omim.org/entry/600886. Accessed Nov. 8, 2017.
Beaumont C. Hyperferritinemia, Hereditary, with Congenital Cataracts. Orphanet. https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=1580&Disease_Disease_Search_diseaseGroup=Hyperferritinemia%E2%80%93Hereditary%E2%80%93with-Congenital-Cataracts&Disease_Disease_Search_diseaseType=Pat&Disease%28s%29/group%20of%20diseases=Hereditary-hyperferritinemia-with-congenital-cataracts&title=Hereditary-hyperferritinemia-with-congenital-cataracts&search=Disease_Search_Simple.%20Last Updated April 2006. Accessed Nov. 8, 2017.
NORD y la Fundación MedicAlert se han asociado en un nuevo programa para brindar protección a pacientes con enfermedades raras en situaciones de emergencia.
Aprende más https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Asegurarse de que los pacientes y los cuidadores estén equipados con las herramientas que necesitan para vivir su mejor vida mientras manejan su condición rara es una parte vital de la misión de NORD.
Aprende más https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/Este programa de asistencia, primero en su tipo, está diseñado para los cuidadores de un niño o adulto diagnosticado con un trastorno raro.
Aprende más https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
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