{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T12:20:42Z","timestamp":1768738842022,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Fabry disease is an X-linked lysosomal disease in which defects in the alpha-galactosidase A enzyme activity lead to the ubiquitous accumulation of glycosphingolipids. Whereas the classic disease is characterized by neuropathic pain, progressive renal failure, white matter lesions, cerebral stroke, and hypertrophic cardiomyopathy (HCM), the non-classic phenotype, also known as cardiac variant, is almost exclusively characterized by HCM. Circulating sphingosine-1-phosphate (S1P) has controversially been associated with the Fabry cardiomyopathy. We measured serum S1P levels in 41 patients of the FFABRY cohort. S1P levels were higher in patients with a non-classic phenotype compared to those with a classic phenotype (200.3 [189.6\u2013227.9] vs. 169.4 ng\/mL [121.1\u2013203.3], p = 0.02). In a multivariate logistic regression model, elevated S1P concentration remained statistically associated with the non-classic phenotype (OR = 1.03; p &lt; 0.02), and elevated lysoGb3 concentration with the classic phenotype (OR = 0.95; p &lt; 0.03). S1P levels were correlated with interventricular septum thickness (r = 0.46; p = 0.02). In a logistic regression model including S1P serum levels, phenotype, and age, age remained the only variable significantly associated with the risk of HCM (OR = 1.25; p = 0.001). S1P alone was not associated with cardiac hypertrophy but with the cardiac variant. The significantly higher S1P levels in patients with the cardiac variant compared to those with classic Fabry suggest the involvement of distinct pathophysiological pathways in the two phenotypes. S1P dosage could allow the personalization of patient management.<\/jats:p>","DOI":"10.3390\/jcm11051233","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T21:11:07Z","timestamp":1645737067000},"page":"1233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sphingosine-1-Phosphate Levels Are Higher in Male Patients with Non-Classic Fabry Disease"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4463-9757","authenticated-orcid":false,"given":"Wladimir","family":"Mauhin","sequence":"first","affiliation":[{"name":"Reference Center for Lysosomal Diseases, Internal Medicine Department, Groupe Hospitalier Diaconesses\u2014Croix Saint Simon, 75020 Paris, France"},{"name":"Center of Research in Myology, UMRS 974, Association Institut de Myologie, INSERM, Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8901-2678","authenticated-orcid":false,"given":"Abdellah","family":"Tebani","sequence":"additional","affiliation":[{"name":"INSERM Unit 1245, Normandie Universit\u00e9s, 76000 Rouen, France"},{"name":"Department of Metabolic Biochemistry, Rouen University Hospital, 76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damien","family":"Amelin","sequence":"additional","affiliation":[{"name":"Center of Research in Myology, UMRS 974, Association Institut de Myologie, INSERM, Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lenaig","family":"Abily-Donval","sequence":"additional","affiliation":[{"name":"INSERM Unit 1245, Normandie Universit\u00e9s, 76000 Rouen, France"},{"name":"Department of Neonatal Pediatrics, Intensive Care and Neuropediatrics, Rouen University Hospital, 76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Foudil","family":"Lamari","sequence":"additional","affiliation":[{"name":"UF Biochimie des Maladies Neuro-Metaboliques, Service de Biochimie M\u00e9tabolique, Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re, AP-HP, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"London","sequence":"additional","affiliation":[{"name":"Reference Center for Lysosomal Diseases, Internal Medicine Department, Groupe Hospitalier Diaconesses\u2014Croix Saint Simon, 75020 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Douillard","sequence":"additional","affiliation":[{"name":"Reference Center for Inborn Metabolic Disease, Jeanne de Flandres Hospital, CHU LILLE, 59037 Lille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertrand","family":"Dussol","sequence":"additional","affiliation":[{"name":"Nephrology Department, Aix Marseille Universit\u00e9 et Centre d\u2019Investigation Clinique 1409, INSERM\/AMU\/AP-HM, 13005 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Leguy-Seguin","sequence":"additional","affiliation":[{"name":"Internal Medicine and Clinical Immunology Department, Francois Mitterrand Hospital, 21000 Dijon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Noel","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Strasbourg University Hospital, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agathe","family":"Masseau","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, H\u00f4tel-Dieu University Hospital, 44000 Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didier","family":"Lacombe","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, CHU de Bordeaux, INSERM U1211, Universit\u00e9 de Bordeaux, 33000 Bordeaux, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne","family":"Maillard","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Huriez Hospital, University of Lille, 59037 Lille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6184-7270","authenticated-orcid":false,"given":"Soumeya","family":"Bekri","sequence":"additional","affiliation":[{"name":"INSERM Unit 1245, Normandie Universit\u00e9s, 76000 Rouen, France"},{"name":"Department of Metabolic Biochemistry, Rouen University Hospital, 76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Lidove","sequence":"additional","affiliation":[{"name":"Reference Center for Lysosomal Diseases, Internal Medicine Department, Groupe Hospitalier Diaconesses\u2014Croix Saint Simon, 75020 Paris, France"},{"name":"Center of Research in Myology, UMRS 974, Association Institut de Myologie, INSERM, Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Benveniste","sequence":"additional","affiliation":[{"name":"Center of Research in Myology, UMRS 974, Association Institut de Myologie, INSERM, Sorbonne Universit\u00e9, 75013 Paris, France"},{"name":"Internal Medicine and Clinical Immunology, Reference Center for Neuromuscular Disorders, AP-HP, Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re, DHUi2B, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1001\/jama.284.21.2771","article-title":"Clinical features of and recent advances in therapy for Fabry 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