CLN2 disease

CLN2 disease, also known as late infantile neuronal ceroid lipofuscinosis (LINCL) or Jansky-Bielschowsky disease, is a rare, inherited lysosomal storage disorder caused by deficiency of the enzyme tripeptidyl peptidase 1 (TPP1). It belongs to the group of neuronal ceroid lipofuscinoses (NCLs), which are collectively the most common neurodegenerative disorders of childhood. The disease results from biallelic pathogenic variants in the TPP1 (CLN2) gene located on chromosome 11p15.4. Deficiency of TPP1 leads to accumulation of ceroid lipofuscin within lysosomes, particularly in neurons, causing progressive neurodegeneration. The classic late infantile form typically presents between ages 2 and 4 years. The first symptom is usually new-onset seizures, often initially presenting as epilepsy. This is followed by progressive language decline, loss of motor skills, ataxia, and myoclonus. Visual impairment progresses to blindness due to retinal degeneration. Cognitive decline is relentless, and affected children typically lose the ability to walk, talk, and interact with their environment. Brain MRI shows progressive cerebral and cerebellar atrophy. Without treatment, the disease follows a rapidly progressive course, with most children becoming severely impaired by age 6 and death typically occurring between ages 8 and 12. An atypical, later-onset form with slower progression has also been described. A significant advance in treatment came with the approval of cerliponase alfa (Brineura), a recombinant form of TPP1 administered directly into the cerebrospinal fluid via intracerebroventricular infusion. This enzyme replacement therapy has been shown to slow the decline in motor and language function in children with CLN2 disease and was approved by the FDA in 2017. Supportive care including antiepileptic medications, physical therapy, nutritional support, and palliative care remain essential components of management. Gene therapy approaches are also under investigation in clinical trials.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about CLN2 disease