Leber Congenital Amaurosis Type 2
Leber Congenital Amaurosis (LCA) is the most severe form of inherited retinal degeneration. LCA is characterized by severely reduced visual acuity (less or equal 20/400) or blindness within the first year of life. (Source Orphanet)
The prevalence of LCA is 1/50 000 – 1/33 000. LCA represents 5% of all retinal dystrophies and 20% of blindness in school age children. (Source Orphanet)
Different types of gene are involved. Mutations in genes encoding retina-specific proteins have been identified in several responsible genes of LCA, e.g. RPE65, AIPL1, CRB1, CRX, GUCY2D, RPGRIP1.
HORAMA is focused on Leber congenital amaurosis type 2 (LCA2).
Leber congenital amaurosis type 2 is due to mutations in the RPE65 gene.
RPE65 mutations represent 3-6% of all LCA cases and 11% of early-onset retinal degeneration. More than 30 RPE65 gene mutations have been described.
The RPE65 protein, located in the RPE, is involved in the visual cycle. RPE65 helps convert all-trans retinal back to 11-cis retinal so the visual pigment can be regenerated. Mutations in the RPE65 gene lead to a disruption of the visual cycle that results in reduced PR function and visual loss from early life.
Clinical presentation of RPE65 patients
An early diagnosis is made as the child shows visually impaired behaviour in the first year(s) of life. After the first decade, an improvement in visual performance is observed, which then deteriorates to reach legal blindness around 30 years of age.
LCA2 is first characterised by a loss of night vision and then of central vision. Occasionally there is an associated photophilia (necessity for exposure to strong light) followed by, as the child ages, a photophobia.
By funduscopy, small whitish, chalky dots can sometimes be seen. This test reveals attenuation of retinal vessels along with variable signs of retinal degeneration.
There are no detectable photopic or scotopic ERG responses from a young age. An absence of retinal autofluorescence has been reported.
Fundus photograph of a 25-year-old individual compound heterozygous for RPE65 mutations IVS1+5g-a and Y368H, and diagnosed with childhood-onset severe retinal dystrophy. (Photograph courtesy of Paul A. Sieving, NEI/NIDCD, Bethesda, MD.) in D.A. Thompson, A. Gal / Progress in Retinal and Eye Research 22 (2003) 683–703