Evaluation of different suspicion indices in identifying patients with Niemann-Pick disease Type C in clinical practice: a post hoc analysis of a retrospective chart review

Orphanet Journal of Rare Diseases

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[1] 0000 0000 9100 9940, grid.411798.2, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic;0000 0001 0663 8628, grid.411160.3, Neuropediatrics, Institut Pediatric Hospital Sant Joan de Déu, Barcelona, Spain;0000000109409708, grid.7634.6, Department of Pediatric Neurology, Comenius University Medical School and National Institute of Children’s Diseases, Bratislava, Slovakia;0000000109409708, grid.7634.6, Department of Pediatrics, Centre for Inborn Errors of Metabolism, Comenius University Medical School and National Institute of Children’s Diseases, Bratislava, Slovakia;Actelion Pharmaceuticals Ltd., a Janssen Pharmaceutical Company of Johnson & Johnson, Allschwil, Switzerland;Syntax for Science S.L, Palma de Mallorca, Spain;grid.411600.2, Department of Paediatric Neurology, Paediatric Neurology Research Centre, Shahid Beheshti University of Medical Sciences, Mofid Children Hospital, Tehran, Iran;

关键词: Niemann-Pick disease Type C;    NP-C;    Clinical diagnosis;    NP-C disability scales;    NP-C Suspicion Index;    Screening;    Neurologic findings;    Patient detection;    Hepatosplenomegaly;    Neonatal jaundice;   

DOI  :  10.1186/s13023-019-1124-3

来源: publisher

【 摘 要 】

BackgroundNiemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder with varying symptomatology depending on the age of onset. The diagnosis of NP-C is challenging due to heterogeneous nonspecific clinical presentation of the disease. NP-C Suspicion Index (SI) was developed to aid screening and identification of patients with suspicion of NP-C for further clinical evaluation. Here we assess the performance of five NP-C SI models to identify patients with NP-C compared with clinical practice to determine the best SI model for identification of each clinical form of NP-C by age.MethodsThis was a post hoc analysis of a retrospective chart review of patient data collected from five expert NP-C centers. The study assessed the proportion of patients with NP-C who could have been identified using the Original SI, Refined SI, 2/7 SI, 2/3 SI, and Early-Onset SI and evaluated the performance of each SI against clinical practice. A score above a threshold of 70 points for the Original SI, 40 points for the Refined SI, 6 points for the Early-Onset SI, and 2 points for the 2/7 and 2/3 SIs represented identification of NP-C.ResultsThe study included 63 patients, and of these, 23.8% had a family history of NP-C. Of the available SI tools, the Refined SI performed well in identifying patients with NP-C across all age groups (77.8% infantile, 100% juvenile and 100% adult groups), and earlier identification than clinical diagnosis would have been possible in 50.0% of infantile, 72.7% of juvenile and 87.0% of adult patients. Patients who were not detected by the Refined SI prior to clinical diagnosis mainly presented with delayed developmental milestones, visceral manifestations, neurologic hypotonia, clumsiness, ataxia, vertical supranuclear gaze palsy, parent or siblings with NP-C, dysarthria/dysphagia and psychotic symptoms.ConclusionThis study demonstrated the applicability of various SI models for screening and identification of patients with NP-C for further clinical evaluation. Although NP-C is rare and the patient population is limited, this study was conducted in a real-world setting and confirms SI models as useful screening tools that facilitate identification of patients with NP-C earlier in their disease course.

【 授权许可】

CC BY