Leber Congenital Amaurosis
Leber Congenital Amaurosis or LCA is an inherited retinal disease that causes severe visual impairment in children. The retina is the lining at the back of the eye. Along with the optic nerve, it forms the ‘nerve’ of the eye. A healthy retina is essential for normal vision. At a cellular level, the retina has 10 layers and the most important of these are the photoreceptors called ‘Rods and Cones’ and the ‘Retinal Pigment Epithelium’. Rods generally help with night vision while cones help with day vision and color vision. The central retina is called the macula; a healthy macula is essential to be able to read fine print, identify colors, faces, and so on.
Genetic conditions like LCA cause severe, progressive loss of the photoreceptors, of both the rods and cones. Parents of the affected child may notice a lack of visual response and roving eye movements in early infancy. As the child grows older, they may notice their child constantly rubbing their eyes. Some forms of LCA may be associated with symptoms that involve organs other than the eye/vision.
Like other genetic conditions, LCA is caused by genetic ‘mutations’. The human body is made up of millions of cells. The genetic code within each cell is contained in the DNA, with the code being arranged as a set of spellings (Nucelotides). These nucleotides get together to form amino acids, which then form proteins. Proteins are essential for every single function within the human body. When an error occurs in these nucleotides (like the spelling mistakes within a word), a mutation occurs. A mutation that affects the normal functioning of the retina can lead to genetic conditions like LCA.
LCA itself is caused by mutations in about two dozen genes. These are mostly transmitted from parents to offspring in an autosomal recessive manner. Each parent carries one copy of the mutated gene (while the other gene is normal). They have no symptoms themselves and are unaffected carriers of the mutation. When such a couple has children, there is a 50% chance that the child inherits one affected copy from one of the parents (while the other copy is normal). This child then becomes an unaffected carrier. 25% of the children however can inherit both the abnormal copies, and they then develop the disease.
Genetic testing is available for LCA and helps understand the various treatment approaches under research, and the appropriate clinical trial.
This is one of the very few inherited retinal diseases for which an approved treatment exists. In December 2017, the USFDA approved gene therapy, “LUXTURNA” for patients with retinal disease caused by two mutations in the RPE65 gene. This is currently the only approved gene therapy for LCA. However, this is not applicable to patients with LCA due to other mutations. Several gene therapy clinical trials are underway for other mutations in LCA.