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.
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.
|Schiffmann, Raphael; Swift, Caren; McNeill, Nathan et al. (2018) Low frequency of Fabry disease in patients with common heart disease. Genet Med 20:754-759|
|Shapiro, Elsa; Ahmed, Alia; Whitley, Chester et al. (2018) Observing the advanced disease course in mucopolysaccharidosis, type IIIA; a case series. Mol Genet Metab 123:123-126|
|Ahrens-Nicklas, Rebecca; Schlotawa, Lars; Ballabio, Andrea et al. (2018) Complex care of individuals with multiple sulfatase deficiency: Clinical cases and consensus statement. Mol Genet Metab 123:337-346|
|Ou, Li; Przybilla, Michael J; Whitley, Chester B (2018) Metabolomics profiling reveals profound metabolic impairments in mice and patients with Sandhoff disease. Mol Genet Metab :|
|McIntosh, Paul T; Hobson-Webb, Lisa D; Kazi, Zoheb B et al. (2018) Neuroimaging findings in infantile Pompe patients treated with enzyme replacement therapy. Mol Genet Metab 123:85-91|
|Nestrasil, Igor; Ahmed, Alia; Utz, Josephine M et al. (2018) Distinct progression patterns of brain disease in infantile and juvenile gangliosidoses: Volumetric quantitative MRI study. Mol Genet Metab 123:97-104|
|Ou, Li; Przybilla, Michael J; Koniar, Brenda et al. (2018) RTB lectin-mediated delivery of lysosomal ?-l-iduronidase mitigates disease manifestations systemically including the central nervous system. Mol Genet Metab 123:105-111|
|Desai, Ankit K; Walters, Crista K; Cope, Heidi L et al. (2018) Enzyme replacement therapy with alglucosidase alfa in Pompe disease: Clinical experience with rate escalation. Mol Genet Metab 123:92-96|
|Sindelar, Miriam; Dyke, Jonathan P; Deeb, Ruba S et al. (2018) Untargeted Metabolite Profiling of Cerebrospinal Fluid Uncovers Biomarkers for Severity of Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2, Batten Disease). Sci Rep 8:15229|
|Shapiro, Elsa G; Whitley, Chester B; Eisengart, Julie B (2018) Beneath the floor: re-analysis of neurodevelopmental outcomes in untreated Hurler syndrome. Orphanet J Rare Dis 13:76|
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