CLN2

CLN2, also known as neuronal ceroid lipofuscinosis type 2 or Batten disease, is a rare lysosomal storage disorder within the neuronal ceroid lipofuscinoses spectrum. It results from biallelic mutations in the TPP1 gene, which encodes the enzyme tripeptidyl peptidase 1. Deficient TPP1 activity leads to accumulation of storage material in lysosomes, particularly in neurons, causing progressive neurodegeneration.

The disease characteristically begins in early childhood, usually between ages 2 and 4, though onset can vary. Early symptoms include seizures, developmental regression, and loss of motor and language skills. As the condition progresses, affected individuals commonly experience ataxia, visual impairment from retinal degeneration, and a broad decline in cognitive function. Epilepsy and behavioral changes are common, and survivors often require substantial supportive care.

Diagnosis is based on clinical features supported by laboratory testing. Reduced or absent TPP1 enzymatic activity in leukocytes or fibroblasts confirms the functional defect, and genetic testing identifies pathogenic variants in TPP1. Brain imaging and electroencephalography may show progressive neurodegenerative changes and characteristic patterns associated with Batten disease.

Management is multidisciplinary and focuses on symptom control and quality of life. Anti-seizure medications, physical and occupational therapy, vision support, and nutritional and palliative care are integral components. A disease-modifying therapy, cerliponase alfa (Brineura), a recombinant human TPP1 enzyme, is administered intraventricularly via an implanted device every two weeks and has been shown to slow neurological decline, though it does not cure the disease. Research continues into gene therapy and other approaches, with ongoing trials underway to expand treatment options.