Early initiation of ERT in Fabry disease can eliminate major organ damage and yield enhanced long-term benefits: Case Study

Fabry disease is an uncommon, X-linked, lysosomal storage disease that leads to defects in the glycosphingolipid metabolic pathway due to absent or deficient lysosomal α-galactosidase (α-Gal A) activity. This results in the accumulation of globotriaosylceramide (GL-3) within lysosomes in a wide range of cells, including cardiac, endothelial, corneal, and renal cells, and consequently, the progressive appearance of clinical symptoms in target organs.

As FD is a progressive condition, it is important to confirm a definitive diagnosis to have timely access to favourite monitoring, appropriate management, and supportive treatment. p1Q2EFCDXZSA

Enzyme replacement therapy (ERT), which involves the exogenous supplementation of α-Gal A enzyme has been successfully administered for treating Fabry disease.

Tianyang Ye, Department of Internal Medicine, The First Navy Hospital of Southern Theater Command, Zhanjiang, Guangdong, China, and colleagues report a case of a 37-year-old male with complaints of recurrent proteinuria and ventricular septal thickening.

A renal biopsy revealed vacuolization and foamy changes in podocytes, and the presence of zebra bodies and myelin-like bodies. α-Gal A activity of the white blood cells was very low, while the Lyso-GL-3 level was high. Additionally, genetic analysis revealed a gene variant c.902G > A p. Arg301Gln.

The patient was diagnosed with Fabry disease and subsequently received intravenous (IV) ERT with a dose of Agalsidase α (0.2 mg/kg, 17.5 mg every two weeks). During the 6-month follow-up, the values of proteinuria and ventricular septum thickness remain stable.

As FD is a progressive disease, the researchers suggest that initiating enzyme replacement therapy at an early age can effectively reduce the deposition of GL-3, attenuate the progressive clinical manifestations of FD, have the potential to eliminate major organ damage and provide greater long-term benefits.

"To our knowledge, FD exhibits a broad spectrum of phenotypic variability ranging from multiorgan involvement to diverse individual differences. Patients with FD diagnosis experience a multisystemic disorder characterized by life-threatening complications, such as progressive renal insufficiency, recurrent strokes, cardiomyopathy, and neuropathic pain, which can lead to Fabry crises," the researchers wrote.

To conclude, the article reported a case of a 37-year-old male admitted with complaints of ventricular septal thickening and proteinuria. Subsequently, he received intravenous ERT with a dose of Agalsidase α.

"As Fabry disease is a progressive disorder, initiating ERT at an early age can effectively decrease the deposition of GL-3, attenuate the progressive clinical manifestations of FD, and provide greater long-term benefits," the researchers wrote.

Reference:

Chen, Z., Yin, B., Jiao, J. et al. Case report: enzyme replacement therapy for Fabry disease presenting with proteinuria and ventricular septal thickening. BMC Nephrol 25, 61 (2024). https://doi.org/10.1186/s12882-024-03499-w