Neuronal ceroid lipofuscinosis 2: A Monster Attacking The Nervous Systems
Neuronal ceroid lipofuscinosis 2 (CLN2) or Batten disease is a lysosomal storage disease which primarily affects the nervous system. This disease is a rare disease. In a province of Canada, the incidence of CLN2 disease is estimated to be 9 in 100.000 births. More than 300 cases worldwide have been described in the scientific literature. Symptoms of the CLN2 generally develop between ages two and four years, although later onset cases have been reported. Children with CLN2 may experience speech delay, seizures that do not respond to medications (intractable), loss of muscle coordination (ataxia), muscle twitches (myoclonus), loss of vision, developmental delay, intellectual disability, and behavioural problems. Symptoms of CLN2 worsen as the child gets older (progressive).
Mutations in the TPP1 gene cause CLN2 disease and the mutations are inherited in an autosomal recessive pattern. The TPP1 gene provides instructions for producing an enzyme called tripeptidyl peptidase 1. Tripeptidyl peptidase 1 breaks down protein fragments, known as peptides, into amino acids. Mutations in the TPP1 gene greatly reduce the production of the tripeptidyl peptidase 1 enzyme. A reduction in functional enzyme results in the incomplete breakdown of certain peptides. CLN2 disease is characterized by the accumulation of proteins or peptides and other substances in cells.
These accumulations occur in cells throughout the body; however, nerve cells seem to be particularly vulnerable to their effects. Genetic testing and enzyme testing are needed to to confirm the diagnosis.
Although there is no medication that can currently cure CLN2, in the Spring of 2017 both the United States Food and Drug Administration (FDA) and the European Commission approved the use of cerliponase alfa (brand name: Brineura) for children with CLN2. In clinical studies, cerliponase alfa was shown to slow down the progression of the disease. In addition, other medications and therapies can help relieve some of the symptoms of CLN2. However, there are currently no patient with CLN2 who have received this enzyme replacement therapy
References:
https://rarediseases.info.nih.gov/diseases/3045/neuronal-ceroid-lipofuscinosis-2
https://ghr.nlm.nih.gov/condition/cln2-disease#resources