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.
|Jarnes Utz, Jeanine R; Kim, Sarah; King, Kelly et al. (2017) Infantile gangliosidoses: Mapping a timeline of clinical changes. Mol Genet Metab 121:170-179|
|Whitley, Chester B (2017) WORLDSymposium™ 2017 Introduction. Mol Genet Metab 120:S2-S6|
|Ou, Li; Przybilla, Michael J; Koniar, Brenda et al. (2017) RTB lectin-mediated delivery of lysosomal ?-l-iduronidase mitigates disease manifestations systemically including the central nervous system. Mol Genet Metab :|
|Solomon, Melani; Muro, Silvia (2017) Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives. Adv Drug Deliv Rev 118:109-134|
|Mauer, Michael; Sokolovskiy, Alexey; Barth, Jay A et al. (2017) Reduction of podocyte globotriaosylceramide content in adult male patients with Fabry disease with amenable GLA mutations following 6 months of migalastat treatment. J Med Genet 54:781-786|
|Eisengart, Julie B; Jarnes, Jeanine; Ahmed, Alia et al. (2017) Long-term cognitive and somatic outcomes of enzyme replacement therapy in untransplanted Hurler syndrome. Mol Genet Metab Rep 13:64-68|
|Rairikar, Mugdha; Kazi, Zoheb B; Desai, Ankit et al. (2017) High dose IVIG successfully reduces high rhGAA IgG antibody titers in a CRIM-negative infantile Pompe disease patient. Mol Genet Metab 122:76-79|
|Ou, Li; Przybilla, Michael J; Whitley, Chester B (2017) Proteomic analysis of mucopolysaccharidosis I mouse brain with two-dimensional polyacrylamide gel electrophoresis. Mol Genet Metab 120:101-110|
|Rairikar, Mugdha V; Case, Laura E; Bailey, Lauren A et al. (2017) Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T>G ""late-onset"" GAA variant. Mol Genet Metab 122:99-107|
|McIntosh, Paul T; Hobson-Webb, Lisa D; Kazi, Zoheb B et al. (2017) Neuroimaging findings in infantile Pompe patients treated with enzyme replacement therapy. Mol Genet Metab :|
Showing the most recent 10 out of 102 publications