Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis

El proceso de enseñanza-aprendizaje y su incidencia en el área socio-afectivo de los niños y niñas de educación inicial de la Unidad Educativa Experimental Fiscal “15 de Octubre” de la ciudad de Jipijapa

La problemática presentada en la Unidad Educativa Experimental Fiscal “15 de Octubre” con el tema del proceso de enseñanza-aprendizaje y su incidencia en el área socio-afectivo de niños y niñas, se realizó un estudio a los involucrados: autoridad, docentes, niños y niñas y padres de familia con la intención de buscar alternativas de solución al problema planteado. Se evidencio que las docentes deben poner en práctica diferentes estrategias para hacer del aprendizaje significativo logros exitosos en el desarrollo de lo socio-afectivo en todo el proceso de enseñanza-aprendizaje (PEA). Los padres de familia no participan activamente en el PEA de sus hijos e hijas. En el área socio-efectivo del plantel no existen muchos juegos y herramientas para desarrollar las estas actividades.O problema apresentado na Unidade de Educação Experimental Fiscal “15 de outubro”, com o tema do processo de ensino-aprendizagem e seu impacto na área socioafetiva de crianças, foi realizado um estudo para os envolvidos: autoridade, professores, crianças emeninas e pais com a intenção de buscar soluções alternativas para o problema proposto. Ficou evidente que os professores devem implementar diferentes estratégias para tornar a aprendizagem significativa conquistas de sucesso no desenvolvimento do socioafetivo ao longo do processo de ensino-aprendizagem (PEA). Os pais não participam ativamente da PEA de seus filhos e filhas. Na área socio-efetiva do campus, não há muitos jogos e ferramentas para desenvolver essas atividades.The problem presented in the Fiscal Experimental Educational Unit “October 15” with the theme of the teaching-learning process and its impact on the socio-affective area of children, a study was carried out to those involved: authority, teachers, children, girls, and parents with the intention of seeking alternative solutions to the problem posed. It was evident that teachers must implement different strategies to make meaningful learning successful achievements in the development of the socio-affective throughout the teaching-learning process (PEA). Parents do not actively participate in the PEA of their sons and daughters. In the socio-effective area of the campus, there are not many games and tools to develop these activities

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C : A prospective observational study

Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with ≥2 clinical signs/symptoms of NP-C were considered 'suspected NP-C' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI ≥70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 [4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores ≥70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis