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PO-0369 A Niemann-pick Disease Type C (np-c) Suspicion Index Tool To Aid Diagnosis In Paediatric Patients
  1. CM Lourenco1,
  2. M Pineda2,
  3. E Mengel3,
  4. B Heron4,
  5. J Imrie5,
  6. SA Jones6,
  7. V van der Linden7,
  8. H Jahnova8,
  9. P Jesina9,
  10. P Karimzadeh10,
  11. V Valayannopoulos11,
  12. JM Torres12,
  13. S Kolb13
  1. 1Clinical Genetics, University of Sao Paulo, São Paulo, Brazil
  2. 2Fundación Hospital Sant Joan de Deu CIBERER, Instituto de Salud Carlos III, Barcelona, Spain
  3. 3Villa Metabolica, ZKJM MC University Mainz, Mainz, Germany
  4. 4Centre Référence Des Maladies Lysosomales, CHU Trousseau APHP, Paris, France
  5. 5Central Manchester and Manchester Children’s Foundation Trust, University of Manchester, Manchester, UK
  6. 6Manchester Centre for Genomic Medicine, Central Manchester Universty Hospitals Foundation Trust, Manchester, UK
  7. 7Paediatrician, Association for Assistance to Disabled Children (AACD), Pernambuco, Brazil
  8. 8Institute of Inherited Metabolic Disorders, Charles University, Prague, Czech Republic
  9. 9Department of Pediatrics and Adolescent Medicine, Charles University, Prague, Czech Republic
  10. 10Pediatric Neurology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  11. 11Centre Référence Des Maladies Héréditaires Du Métabolisme de l’Enfant Et de l’Adulte, Hôpital Universitaire Necker-Enfants Malades, Paris, France
  12. 12Biostatistics, Syntax for Science SL, Basel, Switzerland
  13. 13Global Medical Lead, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland


NP-C is a lysosomal lipid storage disorder caused by mutations in NPC1 or NPC2 genes. NP-C can present with a range of visceral, neurological and psychiatric symptoms that vary with age. A suspicion index (SI) tool was developed to assist clinicians achieve early diagnosis. The tool accurately predicts NP-C in patients >4 years of age but performs poorly in paediatric (≤4 years) patients. The present study aimed to utilise the characteristic symptomatology of NP-C in paediatric patients to develop a novel tool to assist paediatricians to identify patients for NP-C testing.

Paediatric patients were classified according to diagnosis: NP-C suspected and confirmed (n = 106); NP-C suspected but negative (n = 31); control (no suspicion of NP-C; n = 63). Symptomatology data were collected retrospectively by questionnaire and summarised descriptively. The relationships between individual symptoms and likelihood of confirmed diagnosis of NP-C were defined by statistical modelling. The final tool was developed iteratively using combinations of symptoms until optimal discriminatory power was achieved.

The characteristic symptomatology of paediatric NP-C patients was identified; visceral symptoms were more prominent compared with older patients. The new tool discriminates well between NP-C confirmed, NP-C negative and control subjects. Statistical analysis demonstrates superior sensitivity and specificity of the paediatric tool compared to the original tool. The newly developed paediatric NP-C SI tool will help paediatricians to identify more paediatric patients with a high suspicion of NP-C, leading to more referrals for specialist testing thus improving early diagnosis and management of NPC-disease in paediatric patients.

Supported by Actelion Pharmaceuticals Ltd.

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