Publications about genetic testing for metabolic disorders
  1. Assessment of Cardiac Involvement in Fabry Disease (FD) with Native T1 Mapping

Assessment of Cardiac Involvement in Fabry Disease (FD) with Native T1 Mapping

Fritz Roller, Dr. 1 Fuest, Sven 1 Marco Meyer 1 Sebastian Harth, Dr. 1 Dursun Gündüz, MD 1 Pascal Bauer 1 Christian Schneider 1 Prof. Arndt Rolfs, MD 2 Gabriele Anja Krombach 1 Prof. Christian Tanislav, MD 1
1 Justus Liebig University Giessen 2 University of Rostock
February 12, 2019

Mass-spectrometry based quantification of biomarkers is a routine step in the diagnostic workup of many diseases at CENTOGENE. In addition, these well-established tools are increasingly being utilized in research settings. A recent example involved the Fabry Disease (FD)-specific biomarker Lyso-Gb3. Scientists including CENTOGENE’s CEO Prof. A. Rolfs showed that sub-clinical cardiac involvement in FD is accurately reflected by plasma-based Lyso-Gb3 values. The study was published ahead of print in Röfo on February 12th.

Röfo. 2019 Feb 12. doi: 10.1055/a-0836-2723. [Epub ahead of print]

Abstract

PURPOSE:

Fabry disease (FD) is an X-linked multi-organ disorder of lysosomal metabolism with cardiac disease being the leading cause of death. Identifying early FD-specific pathologies is important in the context of maximum therapeutic benefit in these stages. Therefore, the aim of this study was to investigate the value of quantitative cardiac T1 mapping as a potential disease-specific surrogate.

METHODS:

16 consecutive FD patients (9 female, 7 male; median age: 54 years, IQR 17) and 16 control patients (9 female, 7 male; median age: 52 years, IQR 20) were investigated at 1.5 Tesla. Native T1 mapping was performed using a modified look locker inversion recovery sequence (MOLLI) and native T1 times were measured within the septal myocardium at the midventricular short-axis section. Also functional parameters, left ventricular morphology, presence of late-gadolinium enhancement, cTnI- and Lyso-Gb3-Levels were evaluated.

RESULTS:

The median native septal T1 time for FD was 889.0 ms and 950.6 ms for controls (p < 0.003). LGE and positive cTnI values (0.26 ± 0.21) were present in 5 FD patients (31.25 %), and left ventricular hypertrophy (LVH) was present in 4 FD patients (25.00 %). The 4 cTnI and 8 Lyso-Gb3 positive FD patients had significantly lower native T1 values (p < 0.05, respectively p < 0.01). Assuming a T1 cut-off value of 900 ms for the identification of increased cardiac lipid deposit, 9 patients with FD (56.25 %) had pathologic values (4 patients cTnI and 8 patients Lyso-Gb3 positive). Moreover, native septal T1 showed a good negative correlation to Lyso-Gb3 (r = - 0.582; p = 0.018).

CONCLUSION:

A pathologic cardiac native T1 time obviously reflects cardiac involvement in the scope of FD at tissue level. In the future native T1 mapping as an imaging biomarker might allow identification of early stages of cardiac involvement in FD before morphological changes are obvious.

KEY POINTS:

  • Native T1 values are significantly decreased in Fabry disease
  • Native T1 shows promising correlation to cardiac and Fabry-specific biomarkers
  • Native T1 mapping might have great potential for early disease detection and therapy monitoring