Neuronal Ceroid-Lipofuscinoses type 3 (NCL3), also known as CLN3 disease or juvenile NCL, is a rare inherited neurodegenerative disorder that belongs to a group of diseases known as Batten disease. Mutations in the CLN3 gene cause CLN3 disease.
Neuronal ceroid-lipofuscinoses type 3 genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Critical features of neuronal ceroid-lipofuscinoses type 3 (CLN3 disease) include:
- Onset in Childhood or Adolescence: CLN3 disease typically begins in childhood or adolescence, typically between the ages of 5 and 10.
- Visual Impairment: Visual symptoms are often early and prominent. Progressive vision loss, including retinal degeneration, is a characteristic feature.
- Seizures: Seizures are common in individuals with CLN3 disease and may be one of the early signs.
- Motor Decline: Progressive decline in motor skills and coordination occurs over time.
- Cognitive Decline: Individuals with CLN3 disease experience a decline in cognitive abilities, leading to intellectual disability.
- Behavioral Changes: Changes in behavior and personality, including mood swings and aggression, may occur.
- Language Regression: Loss of language skills and communication abilities may be observed.
- Movement Abnormalities: In later stages, individuals may develop movement abnormalities such as tremors and myoclonic jerks.
- Psychiatric Symptoms: Psychiatric symptoms, including anxiety and depression, may manifest.
- Brain Atrophy: Imaging studies may reveal progressive brain atrophy.
CLN3 disease is inherited in an autosomal recessive manner, meaning that affected individuals inherit mutated CLN3 genes from both parents. The CLN3 gene provides instructions for making a protein that plays a role in the function of lysosomes within cells.
As CLN3 disease progresses, affected individuals may experience significant disability, including loss of independent mobility and dependence on caregivers. Unfortunately, CLN3 disease has a progressive and relentless course, leading to premature death, often in late adolescence or early adulthood.
Management of CLN3 disease is primarily supportive, focusing on symptom management and improving the quality of life for affected individuals. Seizures may be treated with antiepileptic medications, and various supportive therapies, including physical and occupational therapy, can help address specific needs.
Genetic counseling is crucial for families affected by CLN3 disease to understand the inheritance pattern, assess the risk of having affected children, and explore reproductive options. Due to the severity of the condition, early diagnosis is essential for initiating appropriate supportive care and interventions.
More Information
Ceroid lipofuscinosis type 3 is caused by mutations in the CLN3 gene encoding betanin, a protein found in the membrane of lysosomes whose function remains unknown. This disease is characterized by the production of lysosomal lipofuscin deposits that, when viewed under the microscope, resemble the outline of a fingerprint.
More than 60 different mutations have been described in patients with CLN3, which can produce the disease in homozygosis and compound heterozygosis. The most frequent variant associated with CLN3 is a 1-kb deletion, which is not included in this analysis. This deletion usually occurs in homozygosis but has also been detected in compound heterozygosis with another mutation in CLN3.
The variant c.597C>A (p.Tyr199Ter) in exon 8 of the CLN3 gene generates the appearance of an early stop codon so that a truncated protein is produced that lacks 239 amino acids at the C-terminal end. Functional studies indicate that the protein is absent in this case.
Neuronal ceroid-lipofuscinoses type 3 genetic testing analyzes the 7 most frequent pathogenic mutations of the CLN3 gene.
The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).
