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

Abstract

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.

• Authors: Sanne J van der Veen, Mohamed El Sayed, Carla E M Hollak, Marion M Brands, C Khya S Snelder, S Matthijs Boekholdt, Liffert Vogt, Susan M I Goorden, André B P van Kuilenburg, Mirjam Langeveld
• Journal: Clinical journal of the American Society of Nephrology : CJASN (Clin J Am Soc Nephrol) Vol. 18 Issue 10 Pg. 1272-1282 (10 01 2023) ISSN: 1555-905X [Electronic] United States
• PMID: 37499686 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 by the American Society of Nephrology.

Chemical References

• Biomarkers

Topics

• Humans
• Male
• Child, Preschool
• Adult
• Female
• Fabry Disease (complications, drug therapy)
• Biomarkers
• Disease Progression
• Kidney
• Risk Assessment