Leber congenital amaurosis 1

Leber Congenital Amaurosis (LCA) Overview

Leber congenital amaurosis, also known as LCA, is a rare genetic eye disorder that affects the retina and causes severe visual impairment or blindness at birth. This condition is characterized by:

• Severe vision loss: People with LCA are often blind at birth or experience significant visual impairment.
• Retinal dystrophy: The retina, which is responsible for converting light into electrical signals sent to the brain, is affected in LCA.
• Genetic inheritance: LCA is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

Symptoms and Characteristics

• Crossed eyes or nystagmus: Some individuals with LCA may experience crossed eyes or pendular nystagmus, which is an involuntary movement of the eyes.
• Sluggish pupillary responses: People with LCA may have sluggish pupillary responses to light.
• Reduced visual acuity: Visual acuity is severely reduced in individuals with LCA, often less than 20/400.

References

• [1] Leber congenital amaurosis (LCA) is a rare genetic eye disorder. Affected infants are often blind at birth. Other symptoms may include crossed eyes or nystagmus. (Source: Search result 2)
• [3] Leber congenital amaurosis (LCA) is an eye disorder that primarily affects the retina. People with this condition typically have severe visual impairment or blindness. (Source: Search result 3)
• [5] Leber congenital amaurosis (LCA) is a rare type of inherited eye disorder that causes severe vision loss at birth. It is the most common cause of inherited blindness in infancy. (Source: Search result 5)
• [8] LCA is characterized by severely reduced visual acuity (less or equal 20/400) or blindness within in the first year of life. Sluggish pupillary responses are also a characteristic feature. (Source: Search result 8)

Severe Vision Loss at Birth

Leber congenital amaurosis (LCA) is a rare inherited eye disorder that causes severe vision loss at birth. The visual impairment tends to be present from the very beginning, with some babies being born with little to no vision.

• Reduced Visual Acuity: Babies born with LCA have severely reduced vision, which can often be detected by parents in the first few months of life.
• Blindness: In many cases, LCA leads to complete blindness or severe visual impairment that cannot be corrected with glasses or contact lenses.
• Other Symptoms:
  • Photophobia (sensitivity to light)
  • Nystagmus (involuntary movements of the eyes)
  • Extreme farsightedness
  • Abnormal pupil reactions

These symptoms can vary in severity and may worsen over time, leading to significant visual impairment. It's essential for parents to be aware of these signs and seek medical attention if they suspect their child is experiencing vision problems.

Prevalence and Age of Onset

LCA affects about 1 in 50,000 to 1 in 33,000 live births, making it a rare but significant cause of inherited blindness. The condition typically becomes apparent at birth or shortly thereafter, with some cases being diagnosed later in infancy.

References:

• [2] Leber congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life.
• [5] The prevalence of LCA is 1/50,000 - 1/33,000 live births and accounts for 5% of all retinal dystrophies and 20% of blindness in school-age children.
• [12] Leber congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life.

Diagnostic Tests for Leber Congenital Amaurosis

Leber congenital amaurosis (LCA) is a rare genetic eye disorder that causes severe visual impairment at birth or in early childhood. Diagnosing LCA can be challenging, but several diagnostic tests can help confirm the condition.

• Electroretinogram (ERG): This test measures the electrical activity of the retina and is often used to diagnose LCA. An ERG can show abnormal responses from the retina, indicating severe visual impairment [9][10].
• Optical Coherence Tomography (OCT) scan: An OCT scan uses low-coherence interferometry to capture high-resolution images of the retina. This test can help identify structural abnormalities in the retina associated with LCA [10].
• Genetic testing: Genetic testing is used to identify mutations in genes associated with LCA, such as RPE65, CRB1, and IMPG2. A 28-gene panel that includes assessment of non-coding variants is ideal for patients with a clinical suspicion or diagnosis of Leber congenital amaurosis [7].
• Sequence analysis: This test involves analyzing the DNA sequence to identify mutations in genes associated with LCA.
• Deletion/duplication analysis: This test identifies deletions or duplications of genetic material that may be associated with LCA.

It's essential to note that a diagnosis of LCA is typically made by an eye care specialist, who will perform an eye exam and use one or more of these diagnostic tests to confirm the condition [10][11].

References: [7] - A 28 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion / diagnosis of Leber congenital amaurosis. [9] - The eye exam alone is often not enough to diagnose LCA. Instead, LCA Is typically diagnosed with a specialized retina test called an electroretinogram. This ... [10] - How is Leber’s congenital amaurosis diagnosed? An eye care specialist will diagnose Leber’s congenital amaurosis. They’ll perform an eye exam to look at your child’s eyes (including inside them). They’ll use electroretinography (ERG) to measure the electrical activity in your child’s retinas. Your child might need an optical coherence tomography (OCT) scan, too. [11] - The purpose of this overview is to increase the clinician's awareness of Leber congenital amaurosis (LCA) / early-onset severe retinal dystrophy (EOSRD) and its clinical phenotypes, genetic causes, and management. ...

Leber Congenital Amaurosis (LCA) Treatment Options

Leber Congenital Amaurosis (LCA) is a rare inherited eye disorder that affects the retina, leading to severe vision loss. While there are no definitive treatments for LCA, researchers have made significant progress in developing therapies to improve vision.

Gene Therapy: A Promising Approach

One of the most promising treatment options for LCA is gene therapy. Gene therapy involves replacing or repairing a faulty gene that causes the disease. In the case of LCA, gene therapy targets the RPE65 gene, which is responsible for producing a protein essential for retinal function.

• According to [2], voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy drug, was approved by the FDA in 2017 for the treatment of LCA caused by mutations to the RPE65 gene.
• A study published in [5] found that gene therapy for Leber's Congenital Amaurosis is safe and effective through 1.5 years after vector administration.

Other Treatment Options

While gene therapy shows promise, other treatment options are being explored:

• Stem Cell Therapy: Researchers are investigating the use of stem cells to repair or replace damaged retinal tissue.
• Drug Therapies: Various medications are being studied for their potential to improve vision in patients with LCA.

Current Status

As of 2024, Luxturna (voretigene neparvovec) is the only FDA-approved treatment for LCA caused by mutations to the RPE65 gene. However, researchers continue to explore new therapies and treatment options to improve vision outcomes for patients with this rare disease.

References:

[1] Sep 10, 2024 - There have been major advances in treatments for inherited retinal diseases, such as gene replacement, stem cell therapy and drug therapies...

[2] by W Chiu · 2021 · Cited by 79 - Among these clinical trials, voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy drug, was approved by the FDA for...

[5] by F Simonelli · 2010 · Cited by 730 - Gene Therapy for Leber's Congenital Amaurosis is Safe and Effective Through 1.5 Years After Vector Administration...

The differential diagnosis for Leber Congenital Amaurosis (LCA) includes several conditions that present with similar symptoms, making it challenging to diagnose accurately.

Conditions to Consider

• Hereditary optic atrophy: This is a rare genetic disorder that affects the optic nerve, leading to progressive vision loss. [1]
• Congenital optic atrophy: This condition involves damage to the optic nerve at birth or shortly after, resulting in visual impairment. [2]
• Retarded myelinization of the optic nerve: This is a rare condition where the optic nerve fails to develop properly, leading to visual problems. [3]
• Syndromic and non-syndromic diseases: LCA can be part of various syndromes or occur as an isolated condition, making differential diagnosis crucial. [4]

Key Factors to Consider

• Age of onset: LCA typically presents at birth or within the first few months of life.
• Visual symptoms: Affected individuals often experience severe visual impairment or blindness.
• Family history: A family history of similar conditions can be a significant factor in diagnosing LCA.

Diagnostic Testing

• Electroretinography (ERG): This test measures the electrical activity of the retina and can help diagnose LCA. [5]
• Genetic testing: Identifying specific genetic mutations associated with LCA can aid in diagnosis. [6]

It's essential to consider these factors and conditions when diagnosing Leber Congenital Amaurosis, as accurate identification is crucial for providing appropriate treatment and management.

References: [1] - Search result 9 [2] - Search result 9 [3] - Search result 9 [4] - Search result 7 [5] - Search result 8 [6] - Search result 5