The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are inherited, autosomal recessive lysosomal storage diseases. Although the NCLs are relatively rare, the childhood variants represent the most common neurodegenerative disorders of childhood, affecting approximately 1:25,000 in the U.S. and with an incidence worldwide as high as 1:12,500. NCL variants are distinguished mainly by their different ages of onset and the rate at which symptoms progress. Juvenile NCL (JNCL), due to the CLN-3 mutation, is one of the more common forms of NCL. Symptom onset for JNCL is between ages 5 to 8, with slow progression until death in the 2nd or 3rd decade of life. The most common early symptoms of JNCL are vision loss, seizures dementia, behavioral difficulties, and impaired motor skills. As the disease progresses, the child becomes increasingly disabled and there is a substantial caregiver burden. There are few quantitative data on the natural history of JNCL. It is known that JNCL includes a broad range of neurological, neuropsychological, and behavioral/psychiatric symptoms. There is progressive loss of speech, language, motor skills, and self-care skills as the disease progresses. In some individuals, aggressive behavior, anxiety, hallucinations, obsessions, or personality changes are prominent. However, it is not known to what degree each type of symptoms contributes to the overall disability and caregiver burden. It is also not known to what degree the seizures and seizure control contributes to disability. Further, it is not known to what extent genotype influences phenotypic variability. We propose three specific aims to determine the natural history of JNCL quantitatively, to characterize the neuropsychological and behavioral phenotype of JNCL, to establish validity and reliability of a rating scale for JNCL, and to determine correlations between phenotype and genotype of individual JNCL subjects. Successful completion of this project will provide the necessary framework for moving forward with clinical trials in this devastating disease. Although JNCL is a rare disease, our research has implications that can be generalized to the study of other degenerative neurologic disorders in children and for preparing translational clinical trials in these diseases.
| Augustine, Erika F; Adams, Heather R; Beck, Christopher A et al. (2015) Standardized assessment of seizures in patients with juvenile neuronal ceroid lipofuscinosis. Dev Med Child Neurol 57:366-71 |
| Mink, Jonathan W; Augustine, Erika F; Adams, Heather R et al. (2013) Classification and natural history of the neuronal ceroid lipofuscinoses. J Child Neurol 28:1101-5 |
| de Blieck, Elisabeth A; Augustine, Erika F; Marshall, Frederick J et al. (2013) Methodology of clinical research in rare diseases: development of a research program in juvenile neuronal ceroid lipofuscinosis (JNCL) via creation of a patient registry and collaboration with patient advocates. Contemp Clin Trials 35:48-54 |
| Augustine, Erika F; Mink, Jonathan W (2013) Enzyme replacement in neuronal storage disorders in the pediatric population. Curr Treat Options Neurol 15:634-51 |
| Dolisca, Sarah-Bianca; Mehta, Mitali; Pearce, David A et al. (2013) Batten disease: clinical aspects, molecular mechanisms, translational science, and future directions. J Child Neurol 28:1074-100 |
| Adams, Heather R; Mink, Jonathan W; University of Rochester Batten Center Study Group (2013) Neurobehavioral features and natural history of juvenile neuronal ceroid lipofuscinosis (Batten disease). J Child Neurol 28:1128-36 |
| Augustine, Erika F; Adams, Heather R; Mink, Jonathan W (2013) Clinical trials in rare disease: challenges and opportunities. J Child Neurol 28:1142-50 |
| Schulz, Angela; Kohlschütter, Alfried; Mink, Jonathan et al. (2013) NCL diseases - clinical perspectives. Biochim Biophys Acta 1832:1801-6 |
| Augustine, Erika F; Blackburn, Joanna; Pellegrino, Joan E et al. (2013) Myoclonus-dystonia syndrome associated with Russell Silver syndrome. Mov Disord 28:841-2 |
| Cialone, Jennifer; Adams, Heather; Augustine, Erika F et al. (2012) Females experience a more severe disease course in Batten disease. J Inherit Metab Dis 35:549-55 |
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