BACKGROUND: Niemann-Pick disease Type C (NP-C) is difficult to diagnose due to heterogeneous and nonspecific clinical presentation. The NP-C Suspicion Index (SI) was developed to identify patients with a high likelihood of NP-C; however, it was less reliable in patients aged <4 years. METHODS: An early-onset NP-C SI was constructed following retrospective chart review of symptom presentation in 200 patients from nine centres comprised of 106 NP-C cases, 31 non-cases and 63 controls. Statistical analyses defined strength of association between symptoms and a diagnosis of NP-C and assigned risk prediction scores to each symptom. RESULTS: Visceral symptoms were amongst the strongest predictors. Except for gelastic cataplexy and vertical supranuclear gaze palsy, central nervous system symptoms were not discriminatory in this population. Performance of the early-onset NP-C SI was superior versus the original NP-C SI in patients aged ≤4 years. CONCLUSIONS: The early-onset NP-C SI can help physicians, especially those with limited knowledge of NP-C, to identify patients aged ≤4 years who warrant further investigation for NP-C.

Actelion Pharmaceuticals Ltd Allschwil Switzerland

Association of Assistance to Deficient Children of Pernambuco Barão de Lucena Hospital Recife PE Brazil

Centre de Référence des Maladies Lysosomales Neuropédiatrie CHU Trousseau APHP Paris France

Centre Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte Necker Enfants Malades and IMAGINE Institute APHP Paris France

Committee for the Evaluation of Treatment for Niemann Pick diseases Paris France

Department of Paediatric Neurology Paediatric Neurology Research Centre Shahid Beheshti University of Medical Sciences Mofid Children Hospital Tehran Iran

Fundació Hospital Sant Joan de Déu Centre for Biomedical Research on Rare Diseases CIBERER Instituto de Salud Carlos 3 Barcelona Spain

Hospital Sant Joan de Deu Passeig de Sant Joan de Deu n°2 Esplugues de Llobregat Barcelona 08950 Spain

Institute of Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Medical Genetics Service Clinics Hospital of Ribeirão Preto University of São Paulo São Paulo Brazil

Niemann Pick UK Vermont House Tyne and Wear Washington UK

Syntax for Science Basel Switzerland

Villa Metabolica Center for Pediatric and Adolescent Medicine MC University of Mainz Mainz Germany

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