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

Castro-Orós, I.; Domenech, M.T.B.; Jesús, Hernandez Gallego; Vidal, M.T.A.; Fdez-Balbuen, C.; Alberti, M.A.; Cebolla, J.J.; Mira, E.; Ruiz, P.G.; Zafra, P.; Rosso, R.E.; Duque, S.C.; Tartari, J.P.; Gamez, J.; Carlos, J.; Martí, M.J.; Santos, F.; Posada, I.; Muñoz, A.; Pueyo, M.J.; Lleó, A.; Naranjo, I.C.; Merino, C.V.; Nieto, J.S.; Sepulveda, J.J.O.; Genis, D.; Miralles, F.C.P.; Yoldi, M.E.; Santamaria, E.; Fons, C.; Costa, J.; Perez, A.G.; Costa, J.F.V.; Vila, T.; Calderon, E.; Rodriguez-Sureda, V.; Lorente, I.; Gonzalez, T.B.; Villarejo, A.; Nomdedeu, B.; Sasieta, F.J.E.; Pocoví, M.; Axpe, I.R.; Villegas, M.D.L.; Laso, E.L.; Rivera, P.M.; Smeyers, P.; Martinez, I.; Arias, M.; Medina, R.C.; Fontes, A.; Ferrer, G.A.; Erro, M.E.; Sobrido, M.J.; del Toro, M.; Sanchez, A.A.; Almenar, C.; Rodrigo, M.; Ripoll, G.P.; Garrido, A.F.; Sierra, C.; Nilda, Venegas Bernal; Esteban, G.; Giné, L.P.; Espinosa, N.R.; Maestre, A.; Gazulla, J.; Martin, A.; Martos, M.L.; Muñoz, J.A.S.; Nuñez, E.; Serra, J.D.; Martin, I.T.; Cantero, B.N.; Lorite, J.B.; Casanova, B.; Ortega, I.P.; Codony, M.B.; San Martin, A.O.H.; Ferro, A.S.; Acebal, M.R.; Leal, R.M.; Moreno, J.M.G.; Bustos, M.D.G.; Aporta, R.; Pascual, B.; Miñana, I.V.; Bustamante, A.; Fernández de la Puebla, F.; Dominguez, C.; Garcia, R.; Poveda, J.A.; Floriach, R.M.; de Rivera, F.J.R.; Gomez, M.A.R.; Pineda, M.; Capablo, J.L.; Maestre, S.J.; Padilla, P.; Turón, E.; Pagonabarraga, J.; Pardo, C.C.; Campos, M.G.; Domingo, R.; Caceres, M.; Calvet, M.S.; Cia, M.T.; Rosso, S.P.; Sivera, R.; Moliner, E.; Fontan, C.; Irún, P.; Clavel, J.; Moreno, A.O.; Santana, C.L.; Torralba, A.O.; Sanz, I.; Aparici, R.C.; Mallén, M.; Modol, R.; Mozas, P.; Fernandez, L.A.; Delgado, T.; Jorda, R.M.S.; Gutierrez-Solana, L.; Hernandez, M.A.; Rabuñal, M.J.; Uranga, J.J.R.; Palomino, A.; Reyes, M.J.S.; Gascón, J.; Loureiro, C.

doi:10.1186/s12967-017-1146-3

000060686 001__ 60686
000060686 005__ 20190709135428.0
000060686 0247_ $$2doi$$a10.1186/s12967-017-1146-3
000060686 0248_ $$2sideral$$a98104
000060686 037__ $$aART-2017-98104
000060686 041__ $$aeng
000060686 100__ $$aCastro-Orós, I.
000060686 245__ $$aAssessment 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
000060686 260__ $$c2017
000060686 5060_ $$aAccess copy available to the general public$$fUnrestricted
000060686 5203_ $$aBackground: 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.
000060686 536__ $$9info:eu-repo/grantAgreement/ES/FIS/PI12-01219
000060686 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000060686 590__ $$a4.197$$b2017
000060686 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b28 / 133 = 0.211$$c2017$$dQ1$$eT1
000060686 592__ $$a1.565$$b2017
000060686 593__ $$aMedicine (miscellaneous)$$c2017$$dQ1
000060686 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2017$$dQ1
000060686 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000060686 700__ $$aIrún, P.
000060686 700__ $$aCebolla, J.J.
000060686 700__ $$aRodriguez-Sureda, V.
000060686 700__ $$aMallén, M.
000060686 700__ $$aPueyo, M.J.
000060686 700__ $$aMozas, P.
000060686 700__ $$aDominguez, C.
000060686 700__ $$0(orcid)0000-0001-8807-9187$$aPocoví, M.$$uUniversidad de Zaragoza
000060686 700__ $$aBustamante, A.
000060686 700__ $$aOrtega, I.P.
000060686 700__ $$aRivera, P.M.
000060686 700__ $$aPalomino, A.
000060686 700__ $$aCaceres, M.
000060686 700__ $$aMaestre, S.J.
000060686 700__ $$aCalderon, E.
000060686 700__ $$aUranga, J.J.R.
000060686 700__ $$aLorite, J.B.
000060686 700__ $$aBustos, M.D.G.
000060686 700__ $$aMoreno, J.M.G.
000060686 700__ $$aGonzalez, T.B.
000060686 700__ $$aMuñoz, A.
000060686 700__ $$aAcebal, M.R.
000060686 700__ $$aMedina, R.C.
000060686 700__ $$aNieto, J.S.
000060686 700__ $$aNuñez, E.
000060686 700__ $$aSierra, C.
000060686 700__ $$aCampos, M.G.
000060686 700__ $$aFernández de la Puebla, F.
000060686 700__ $$aSepulveda, J.J.O.
000060686 700__ $$aLaso, E.L.
000060686 700__ $$aMaestre, A.
000060686 700__ $$aMartos, M.L.
000060686 700__ $$aZafra, P.
000060686 700__ $$aRosso, S.P.
000060686 700__ $$aRosso, R.E.
000060686 700__ $$aReyes, M.J.S.
000060686 700__ $$aFernandez, L.A.
000060686 700__ $$aMoreno, A.O.
000060686 700__ $$aPardo, C.C.
000060686 700__ $$aMartin, A.
000060686 700__ $$aPoveda, J.A.
000060686 700__ $$aCantero, B.N.
000060686 700__ $$aRuiz, P.G.
000060686 700__ $$aRodrigo, M.
000060686 700__ $$aPosada, I.
000060686 700__ $$aFerro, A.S.
000060686 700__ $$aJesús, Hernandez Gallego
000060686 700__ $$aVillarejo, A.
000060686 700__ $$aSan Martin, A.O.H.
000060686 700__ $$aPerez, A.G.
000060686 700__ $$ade Rivera, F.J.R.
000060686 700__ $$aSanz, I.
000060686 700__ $$aSantos, F.
000060686 700__ $$aGutierrez-Solana, L.
000060686 700__ $$aFontan, C.
000060686 700__ $$aDuque, S.C.
000060686 700__ $$aLeal, R.M.
000060686 700__ $$aGamez, J.
000060686 700__ $$aSantamaria, E.
000060686 700__ $$adel Toro, M.
000060686 700__ $$aDelgado, T.
000060686 700__ $$aLorente, I.
000060686 700__ $$aLleó, A.
000060686 700__ $$aPagonabarraga, J.
000060686 700__ $$aCalvet, M.S.
000060686 700__ $$aTurón, E.
000060686 700__ $$aMoliner, E.
000060686 700__ $$aPascual, B.
000060686 700__ $$aAlmenar, C.
000060686 700__ $$aTorralba, A.O.
000060686 700__ $$aFloriach, R.M.
000060686 700__ $$aNilda, Venegas Bernal
000060686 700__ $$aVillegas, M.D.L.
000060686 700__ $$aGiné, L.P.
000060686 700__ $$aNomdedeu, B.
000060686 700__ $$aMartí, M.J.
000060686 700__ $$aDomenech, M.T.B.
000060686 700__ $$aGascón, J.
000060686 700__ $$aCosta, J.
000060686 700__ $$aFons, C.
000060686 700__ $$aPineda, M.
000060686 700__ $$aVidal, M.T.A.
000060686 700__ $$aMira, E.
000060686 700__ $$aTartari, J.P.
000060686 700__ $$aAparici, R.C.
000060686 700__ $$aSanchez, A.A.
000060686 700__ $$aCodony, M.B.
000060686 700__ $$aAlberti, M.A.
000060686 700__ $$aRipoll, G.P.
000060686 700__ $$aModol, R.
000060686 700__ $$aGenis, D.
000060686 700__ $$aSivera, R.
000060686 700__ $$aCosta, J.F.V.
000060686 700__ $$aMartinez, I.
000060686 700__ $$aSmeyers, P.
000060686 700__ $$aVila, T.
000060686 700__ $$aCasanova, B.
000060686 700__ $$aMiralles, F.C.P.
000060686 700__ $$aSerra, J.D.
000060686 700__ $$aMiñana, I.V.
000060686 700__ $$aMerino, C.V.
000060686 700__ $$aGarcia, R.
000060686 700__ $$aJorda, R.M.S.
000060686 700__ $$aClavel, J.
000060686 700__ $$aSantana, C.L.
000060686 700__ $$0(orcid)0000-0003-2181-8461$$aCapablo, J.L.$$uUniversidad de Zaragoza
000060686 700__ $$0(orcid)0000-0002-7284-8890$$aGazulla, J.$$uUniversidad de Zaragoza
000060686 700__ $$aPadilla, P.
000060686 700__ $$aLoureiro, C.
000060686 700__ $$aFdez-Balbuen, C.
000060686 700__ $$aArias, M.
000060686 700__ $$aRabuñal, M.J.
000060686 700__ $$aSobrido, M.J.
000060686 700__ $$aCia, M.T.
000060686 700__ $$aYoldi, M.E.
000060686 700__ $$aErro, M.E.
000060686 700__ $$aFontes, A.
000060686 700__ $$aAxpe, I.R.
000060686 700__ $$aSasieta, F.J.E.
000060686 700__ $$aCarlos, J.
000060686 700__ $$aEsteban, G.
000060686 700__ $$aMuñoz, J.A.S.
000060686 700__ $$aEspinosa, N.R.
000060686 700__ $$aHernandez, M.A.
000060686 700__ $$aMartin, I.T.
000060686 700__ $$aGarrido, A.F.
000060686 700__ $$aAporta, R.
000060686 700__ $$aDomingo, R.
000060686 700__ $$aNaranjo, I.C.
000060686 700__ $$aGomez, M.A.R.
000060686 700__ $$aFerrer, G.A.
000060686 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000060686 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000060686 773__ $$g15, 43 (2017), [11 pp.]$$pJournal of Translational Medicine$$tJournal of Translational Medicine$$x1479-5876
000060686 8564_ $$s1124777$$uhttps://zaguan.unizar.es/record/60686/files/texto_completo.pdf$$yVersión publicada
000060686 8564_ $$s88567$$uhttps://zaguan.unizar.es/record/60686/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000060686 909CO $$ooai:zaguan.unizar.es:60686$$particulos$$pdriver
000060686 951__ $$a2019-07-09-11:31:00
000060686 980__ $$aARTICLE

Universidad de Zaragoza Repository