examining developmental outcomes of children diagnosed with cln2 disease

Conditions: Batten Disease; CLN2; Neuronal Ceroid-Lipofuscinoses

Summary: the investigators propose a study to assess cognitive and developmental outcomes of patients with cln2 that are untreated and receiving cerliponase alfa. this study aims to validate standardized assessment measures to establish a standard of care. the secondary aim is to compare cognitive and developmental outcomes of patients with cln2 that are receiving celiponase alfa to a natural history cohort. to accomplish specific aims of the study, the investigators will use a multi-method approach to collect retrospective data collected as standard of care and prospective developmental data in children with cln2 disease. the investigators will use a combination of standardized measures that include direct assessment and parent report of child development. the investigators focus will also include multiple measures of development including language, motor, social-emotional, and adaptive functioning.

cln2 disease is a predominantly late infantile form of neuronal ceroid lipofuscinosis and one of the many genetic isoforms of batten disease. mutations in the cln2 gene are characterized by deficient lysosomal serine protease tpp1, an enzyme that metabolizes intracellular lysosomal storage materials. accumulations of intracellular deposits occur over time and in many organs of individuals with cln2 disease and lead to neurodegeneration and, eventually, death. cln2 disease is an extremely rare genetic disease affecting around 1 per 200,000 live births. symptoms emerge early in life typically between the ages of 2 and 4 years of age and include seizures, as well as loss of motor, language, and vision functioning. development further declines in early childhood and by age 6 years, children with cln2 are often unable to walk or sit unsupported and become blind. the progression of the disease is rapid with death typically occurring in mid-childhood between the ages of 10 and 15 years of age. recently, enzyme replacement therapy (ert), cerliponase alfa, which is a recombinant form of human tppi, was the first fda-approved treatment to slow the progression of motor decline in children with cln2. cerliponase alfa is expected to restore tpp1 enzyme activity in the brain and alter neurodegeneration and disease progression. animal models suggest promising treatment outcomes as cerliponase alfa significantly delayed the onset of clinical signs, preserved motor and cognitive function, and prolonged life. initial results from a clinical trial further demonstrated that patients receiving cerliponase alfa had less motor declines, as measured by the cln2 clinical rating scale, compared to a natural history cohort. despite these promising results, little is known about the trajectory of other developmental domains, including language, social-emotional, and adaptive functioning of children receiving cerliponase alfa. likewise, the developmental trajectory of untreated patients with cln2 is not well understood. therefore, it is important to understand developmental outcomes and the progression of cln2 in a natural history cohort in order to compare the effectiveness of treatment outcomes.

Eligibility criteria:
inclusion criteria: * patients that have a tpp1 enzyme deficiency * patients have confirmed molecular diagnosis of pathogenic variants in the tpp1 gene * patients that are enrolled in post-marketing studies will be allowed to enroll into the current study exclusion criteria: * patients without a diagnosis of cln2 and deficiency of tpp1 * patients that are currently enrolled as part of a larger multi-center clinical trial