Early start of enzyme replacement therapy in pediatric male patients with classical Fabry disease is associated with attenuated disease progression

Mol Genet Metab. 2022 Feb;135(2):163-169. doi: 10.1016/j.ymgme.2021.12.004.

PMID: 35033446

S J van der Veen, S Körver, A Hirsch

Highlights: Start of treatment with enzyme replacement therapy (ERT) before age 16, in male classical Fabry disease (cFD) patients, is associated with reduced occurrence of renal and cardiac manifestations of Fabry disease (FD), as assessed by intermediate endpoints.

Abstract

Background: Enzyme replacement therapy (ERT) decreases Fabry disease (FD) progression, especially when started before permanent organ damage occurs. However, given the long-term asymptomatic progression of renal, cardiac, and cerebral disease symptoms, the best time to start ERT remains unknown.

Methods: Seven male FD patients with a classical disease phenotype (cFD) who started treatment with agalsidase-beta in childhood were examined after 10 years of medication in this cross-sectional retrospective investigation (median age at evaluation 24 years, range 14-26). These patients' cardiac imaging (echocardiography and MRI), electrophysiological, and biochemical data were compared to untreated male cFD patients (n = 23, median age 22 years, range 13-27 years).

Results: When compared to untreated individuals (ACR 0-248 mg/mmol, median 3.7, p = 0.02), albuminuria was less common and less severe in treated patients (ACR 0-8.8 mg/mmol, median 0.4). Using echocardiography (median 80 g/m2 compared 94 g/m2 , p = 0.02) and MRI (median 53 g/m versus 68 g/m, p = 0.02), the treated group had a decreased left ventricular mass (median 80 g/m2 versus 94 g/m2 , p = 0.02). All the patients who were included in the study did not have myocardial fibrosis. All treated individuals had normal eGFR, but 7/23 (30%) of untreated patients had abnormal eGFR. Cerebral manifestations did not differ.

Conclusion: As measured by intermediate endpoints, starting ERT treatment before the age of 16 in male cFD patients is related with a lower frequency of renal and cardiac manifestations of FD. A decade of follow-up is required to confirm that this technique delays or even prevents renal failure and cardiac events.

Keywords: Disease phenotype, Early treatment, Enzyme replacement therapy, Fabry disease