NORD gratefully acknowledges Joshua L. Dunaief, MD, PhD, Associate 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. In some cases, a mutation may occur randomly as the result of a spontaneous genetic change (sporadically). Hyperferritinemia-cataract syndrome 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 regardless of the sex of the resulting child.
Investigators have determined that the FTL gene is located on the long arm (q) of chromosome 19 (19q13.3-q13.4). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 19q13.3-q13.4” refers to bands 13.3-13.4 on the long arm of chromosome 19. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
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.
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.
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