Federica Deodato1, Sara Boenzi2, Roberta Taurisano3, Michela Semeraro4, Elisa Sacchetti5, Rosalba Carrozzo6, Carlo Dionisi-Vici7. 1. Clinical Division and Research Unit of Metabolic Diseases, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy. Electronic address: federica.deodato@opbg.net. 2. Clinical Division and Research Unit of Metabolic Diseases, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy. Electronic address: sara.boenzi@opbg.net. 3. Clinical Division and Research Unit of Metabolic Diseases, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy. Electronic address: roberta.taurisano@opbg.net. 4. Clinical Division and Research Unit of Metabolic Diseases, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy. Electronic address: michela.semeraro@opbg.net. 5. Clinical Division and Research Unit of Metabolic Diseases, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy. Electronic address: elisa.sacchetti@opbg.net. 6. Unit of Neuromuscular Diseases, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy. Electronic address: rosalba.carrozzo@opbg.net. 7. Clinical Division and Research Unit of Metabolic Diseases, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy. Electronic address: carlo.dionisivici@opbg.net.
Abstract
BACKGROUND: Although representing two distinct disease entities, Niemann-Pick disease type C (NP-C) disease and acid sphingomyelinase deficiency (ASMD) share several phenotypic features. The lack of biomarkers was responsible in the past of diagnostic delay. Recently, plasma oxysterols, cholestan-3β,5α,6β-triol (Triol) and 7-ketocholesterol (7-KC) and lysosphingolipids, Lyso-sphingomyelin (Lyso-SM) and Lysosphingomyelin-509 (Lyso-SM-509), have been proposed as diagnostic biomarkers. We aimed to assess the diagnostic power of the two biomarkers categories and to evaluate possible correlations with patients' age and clinical phenotypes. PATIENTS AND METHODS: We analyzed plasma oxysterols and lysosphingolipids in patients affected by NP-C and ASMD, and compared with healthy controls. RESULTS: Oxysterols were always increased in both NP-C and ASMD. In NP-C, Lyso-SM and Lyso-SM-509 were increased in 70%, and 100% of patients, respectively. Biomarkers negatively correlated with patients' age, with highest levels in early-infantile, intermediate in the late-infantile and lowest in the juvenile phenotype. In ASMD, lysosphingolipids were both increased, with a greater order of magnitude than in NP-C, with highest levels in chronic-neurovisceral vs visceral phenotype. CONCLUSIONS: Lysosphingolipids are useful biomarkers for a rapid and precise diagnosis, allowing clear distinction between NP-C and ASMD. They are more reliable biomarkers than oxysterols and correlate with patients' age and clinical phenotype.
BACKGROUND: Although representing two distinct disease entities, Niemann-Pick disease type C (NP-C) disease and acid sphingomyelinase deficiency (ASMD) share several phenotypic features. The lack of biomarkers was responsible in the past of diagnostic delay. Recently, plasma oxysterols, cholestan-3β,5α,6β-triol (Triol) and 7-ketocholesterol (7-KC) and lysosphingolipids, Lyso-sphingomyelin (Lyso-SM) and Lysosphingomyelin-509 (Lyso-SM-509), have been proposed as diagnostic biomarkers. We aimed to assess the diagnostic power of the two biomarkers categories and to evaluate possible correlations with patients' age and clinical phenotypes. PATIENTS AND METHODS: We analyzed plasma oxysterols and lysosphingolipids in patients affected by NP-C and ASMD, and compared with healthy controls. RESULTS:Oxysterols were always increased in both NP-C and ASMD. In NP-C, Lyso-SM and Lyso-SM-509 were increased in 70%, and 100% of patients, respectively. Biomarkers negatively correlated with patients' age, with highest levels in early-infantile, intermediate in the late-infantile and lowest in the juvenile phenotype. In ASMD, lysosphingolipids were both increased, with a greater order of magnitude than in NP-C, with highest levels in chronic-neurovisceral vs visceral phenotype. CONCLUSIONS:Lysosphingolipids are useful biomarkers for a rapid and precise diagnosis, allowing clear distinction between NP-C and ASMD. They are more reliable biomarkers than oxysterols and correlate with patients' age and clinical phenotype.
Authors: Rohini Sidhu; Pamela Kell; Dennis J Dietzen; Nicole Y Farhat; An Ngoc Dang Do; Forbes D Porter; Elizabeth Berry-Kravis; Janine Reunert; Thorsten Marquardt; Roberto Giugliani; Charles M Lourenço; Raymond Y Wang; Nina Movsesyan; Ellen Plummer; Jean E Schaffer; Daniel S Ory; Xuntian Jiang Journal: Mol Genet Metab Date: 2020-11-18 Impact factor: 4.797
Authors: Eugen Mengel; Marc C Patterson; Rosalia M Da Riol; Mireia Del Toro; Federica Deodato; Matthias Gautschi; Stephanie Grunewald; Sabine Grønborg; Paul Harmatz; Bénédicte Héron; Esther M Maier; Agathe Roubertie; Saikat Santra; Anna Tylki-Szymanska; Simon Day; Anne Katrine Andreasen; Marie Aavang Geist; Nikolaj Havnsøe Torp Petersen; Linda Ingemann; Thomas Hansen; Thomas Blaettler; Thomas Kirkegaard; Christine Í Dali Journal: J Inherit Metab Dis Date: 2021-09-07 Impact factor: 4.750
Authors: Eugen Mengel; Bruno Bembi; Mireia Del Toro; Federica Deodato; Matthias Gautschi; Stephanie Grunewald; Sabine Grønborg; Bénédicte Héron; Esther M Maier; Agathe Roubertie; Saikat Santra; Anna Tylki-Szymanska; Simon Day; Tara Symonds; Stacie Hudgens; Marc C Patterson; Christina Guldberg; Linda Ingemann; Nikolaj H T Petersen; Thomas Kirkegaard; Christine Í Dali Journal: Orphanet J Rare Dis Date: 2020-11-23 Impact factor: 4.123