Early Risk Stratification for Natural Disease Course in Fabry Patients Using Plasma Globotriaosylsphingosine Levels.

Autor:	van der Veen SJ; Department of Endocrinology and Metabolism , Amsterdam UMC location University of Amsterdam, Amsterdam , The Netherlands., Sayed ME; Department of Endocrinology and Metabolism , Amsterdam UMC location University of Amsterdam, Amsterdam , The Netherlands., Hollak CEM; Department of Endocrinology and Metabolism , Amsterdam UMC location University of Amsterdam, Amsterdam , The Netherlands., Brands MM; Division of Metabolic Diseases , Department of Pediatrics , Emma Children's Hospital , Amsterdam UMC location University of Amsterdam, Amsterdam , The Netherlands., Snelder CKS; Department of Endocrinology and Metabolism , Amsterdam UMC location University of Amsterdam, Amsterdam , The Netherlands., Boekholdt SM; Department of Cardiology , Amsterdam UMC location University of Amsterdam, Amsterdam , The Netherlands., Vogt L; Department of Nephrology , Amsterdam UMC location University of Amsterdam, Amsterdam , The Netherlands., Goorden SMI; Amsterdam Gastroenterology, Endocrinology and Metabolism , Amsterdam , The Netherlands.; Laboratory Genetic Metabolic Diseases , Amsterdam UMC location University of Amsterdam, Amsterdam , The Netherlands., van Kuilenburg ABP; Amsterdam Gastroenterology, Endocrinology and Metabolism , Amsterdam , The Netherlands.; Laboratory Genetic Metabolic Diseases , Amsterdam UMC location University of Amsterdam, Amsterdam , The Netherlands., Langeveld M; Department of Endocrinology and Metabolism , Amsterdam UMC location University of Amsterdam, Amsterdam , The Netherlands.
Jazyk:	angličtina
Zdroj:	Clinical journal of the American Society of Nephrology : CJASN [Clin J Am Soc Nephrol] 2023 Oct 01; Vol. 18 (10), pp. 1272-1282. Date of Electronic Publication: 2023 Jul 27.
DOI:	10.2215/CJN.0000000000000239
Abstrakt:	Background: Fabry disease is a very heterogeneous X-linked lysosomal storage disease. Disease manifestations in the kidneys, heart, and brain vary greatly, even between patients of the same sex and with the same disease classification (classical or nonclassical). A biomarker with a strong association with the development of disease manifestations is needed to determine the need for Fabry-specific treatment and appropriate frequency of follow-up because clinical manifestations of the disorder may take decennia to develop. Methods: We investigated the levels of plasma lysoGb3 levels over time and its association with disease manifestations and disease course in 237 untreated patients with Fabry disease (median age 42 years, 38% male) using linear mixed-effect models. Results: LysoGb3 levels are stable over time in plasma of untreated patients with Fabry disease. Higher levels of lysoGb3 were associated with steeper decline in eGFR ( P = 0.05) and a faster increase in albuminuria (measured as the urinary albumin-to-creatinine ratio, P < 0.001), left ventricular mass (measured on echocardiography, P < 0.001), left atrial volume index ( P = 0.003), and Fazekas score ( P = 0.003). In addition, regardless of age, higher lysoGb3 levels were associated with higher relative wall thickness ( P < 0.001) and unfavorable functional markers on echocardiography, including septal mitral annular early diastolic velocity (e', P < 0.001) and the ratio of early transmitral velocity (E) to e' (E/e', P = 0.001). Conclusions: In an individual patient with Fabry disease, the plasma lysoGb3 level reached a specific level in early childhood which, in the absence of Fabry-specific treatment, remained stable throughout life. The level of lysoGb3 in untreated patients was associated with nearly all Fabry-specific disease manifestations, regardless of the sex of the patient. (Copyright © 2023 by the American Society of Nephrology.)
Databáze:	MEDLINE
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