Niemann-Pick disease, type C (NPC) is a pan-ethnic, autosomal recessive lysosomal storage disease with a prevalence between 1/120,000 and 1/150,000. Because of the devastating effects of this illness on patients and families, the public health burden of this disease is disproportionate to its prevalence. Most patients experience a progressive dementia accompanied by vertical supranuclear gaze palsy ataxia, dysarthria, dysphagia, dystonia and in some cases, epilepsy and cataplexy. Several potential human therapeutic agents have been studied in vitro and in animal models of NPC. Before human therapeutic trials can be pursued, it is essential to define the clinical course of NPC, and to identify clinical, neuropsychological and laboratory markers of disease burden and progression. The purpose of this study is to test the hypothesis that patients with NPC will demonstrate a specific pattern of neurocognitive deficits that will be present prior to development of significant neurological deficits and that will correlate with disease progression. Subjects will be recruited from participants in studies at two network sites - the NIH Clinical Center and Mayo Clinic, and will be examined using a standardized set of instruments on an annual basis for the five years of the longitudinal study.
Niemann-Pick disease type C is a neurodegenerative LSD characterized by progressive cognitive loss;a natural history study is proposed to define the clinical course of the disease and identify markers that correlate with disease progression for future clinical trials.
|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|
|Ou, L; Przybilla, M J; Whitley, C B (2018) SAAMP 2.0: An algorithm to predict genotype-phenotype correlation of lysosomal storage diseases. Clin Genet 93:1008-1014|
|Eisengart, Julie B; Rudser, Kyle D; Xue, Yong et al. (2018) Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison. Genet Med 20:1423-1429|
|Kazi, Zoheb B; Desai, Ankit K; Troxler, R Bradley et al. (2018) An immune tolerance approach using transient low-dose methotrexate in the ERT-naïve setting of patients treated with a therapeutic protein: experience in infantile-onset Pompe disease. Genet Med :|
Showing the most recent 10 out of 118 publications