Leber's congenital amaurosis

Leber's congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life, and affects around 1 in 80,000 of the population.

It was first described by Theodor Leber in the 19th century. It should not be confused with Leber's hereditary optic neuropathy, which is a different disease also described by Theodor Leber.

Presentation
Amaurosis refers to a loss of vision not associated with a lesion, and congenital refers to a condition present from birth (not acquired). However, beyond these general descriptions, the presentation of LCA can vary, because it is associated with multiple genes.

LCA is typically characterized by nystagmus, sluggish or no pupillary responses, and severe vision loss or blindness.

Genetics
It is an autosomal recessive disorder thought to be caused by abnormal development of photoreceptor cells.

There is evidence tying type 1 LCA to, and type 2 to.

Other genes which have been implicated include, , and.

OMIM currently recognizes 11 types of LCA:

The gene has been associated with Joubert syndrome, as well as type 10 LCA.

Testing
Project 3000, a foundation started by Pittsburgh Pirates first baseman Derrek Lee and Boston Celtics owner Wyc Grousbeck, works to have the approximately 3,000 people in the United States with the disease genetically tested.

Genetic tests and research are currently being performed at the University of Iowa Carver Lab by Drs. Edwin Stone and Val Sheffield. Dr. Sue Rowland at the University of Florida has recently restored sight in an avian model using gene therapy.

Treatment
Gene therapy treatments are still in the trial phase but there have been successes. The results of a phase 1 trial conducted, by the University of Pennsylvania and Children’s Hospital of Philadelphia and published in 2009, showed sustained improvement in 12 subjects (ages 8 to 44) with RPE65-associated LCA after treatment with AAV2-hRPE65v2, a gene replacement therapy. Early intervention was associated with better results. In that study patients were excluded based on the presence of particular antibodies to the vector AAV2 and treatment was only administered to one eye as a precaution. A 2010 study testing the effect of administration of AAV2-hRPE65v2 in both eyes in animals with antibodies present suggested that immune responses may not complicate use of the treatment in both eyes.

Researchers at Children's Hospital of Philadelphia and the University of Pennsylvania have treated six young people via gene therapy. Eye Surgeon Dr. Al Maguire and gene therapy expert Dr. Jean Bennett developed the technique used by the Children's Hospital.

In Popular Culture

 * In the episode The Blackout in the Blizzard of the television drama Bones, Dr. Jack Hodgins and his pregnant wife Angela Montenegro, who is an LCA carrier, have to wait during a citywide blackout for Hodgins's genetic test results, to see if he is also an LCA carrier. He does indeed turn out to be a carrier, giving their unborn child a 25% chance of having LCA.


 * In the television series ER (season 14, episode 12) Dr. Abby Lockhart diagnoses a young foster girl with Leber's congenital amaurosis. The girl to this point hid her condition from her foster families. The episode contains some information about symptoms, clinical diagnosis and mentions gene replacement therapy and clinical trials as hope for help in managing the condition.