Clinical, genotypic, and neuropsychological profile in a series of cases of patients with Niemann-Pick type C disease

Author:

Mendes Rita1,Valle Daniel1,Bara Tiago1,Furlin Vanessa2,Zeny Michelle3,Santos Mara3,Cordeiro Mara L.4ORCID

Affiliation:

1. Faculdades Pequeno Principe

2. Instituto de Pesquisa Pelé Pequeno Príncipe: Instituto de Pesquisa Pele Pequeno Principe

3. Hospital Pequeno Principe

4. University of California Los Angeles David Geffen School of Medicine

Abstract

Abstract

Background Niemann-Pick type C (NPC) disease is a rare neurodegenerative disorder with a wide spectrum of clinical manifestations and genetic variability. This cross-sectional study aimed to comprehensively describe the neuropsychological impact of NPC and investigate its correlation with specific genotypes. Results Eight patients from six unrelated families were included in this study. The age at symptom onset ranged from 2–16 years, with all patients presenting with ataxia, dysarthria, and cognitive impairment. Following the initiation of miglustat treatment, five patients showed a decrease in the Scale for the Assessment and Rating of Ataxia (SARA) score, whereas two demonstrated subsequent increases. Brain magnetic resonance imaging scans were performed in five patients, revealing white matter abnormalities and/or brain volumetric reduction in three cases. Despite the small sample size, the overall cognitive performance of the cohort was significantly below average. The Family Environmental Scale highlighted positive structural patterns, particularly regarding Personal Growth and System Maintenance. Genetic analysis identified five mutations in the NPC1 gene, correlating with the severity of impairments and clinical outcomes. Conclusions This study highlighted a consistent association between cognitive and behavioral impairments, with severity correlating with age and specific genetic variants. Notably, a subgroup showed a higher prevalence of psychotic and behavioral symptoms, suggesting a potential link with specific genetic variants.

Publisher

Research Square Platform LLC

Reference36 articles.

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3. 1, 2 and Aida Bertoli-Avella. At a glance: The largest Niemann-Pick type C1 cohort with 602 patients diagnosed over 15 years;Moreno PG;Mol Genet Metab,2023

4. Using whole-exome sequencing to investigate the genetic bases of lysosomal storage diseases of unknown etiology;Wang N;Hum Mutat,2017

5. Niemann-Pick disease type C clinical database: Cognitive and coordination deficits are early disease indicators;Stampfer M;Orphanet J Rare Dis,2013

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