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Endothelial markers and homocysteine in patients with classic Fabry disease
1Department of Biochemistry, Hôpital Européen Georges Pompidou, Paris, France.
Insights
Elevated homocysteine and vascular cell adhesion molecule-1 were found in Fabry disease patients, but did not serve as reliable markers for enzyme replacement therapy (ERT) efficacy. Further research is needed, but folic acid may help manage this vascular risk factor.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- Fabry disease is an X-linked genetic disorder of glycosphingolipid metabolism.
- Deficient alpha-galactosidase A activity leads to multisystem complications, including kidney, heart, and brain issues.
- Enzyme replacement therapy (ERT) is available, necessitating reliable markers to track organ damage and treatment effectiveness.
Purpose of the Study:
- To investigate endothelial factors and homocysteine levels as potential surrogate markers for monitoring ERT efficacy in Fabry disease.
- To establish baseline levels of these markers in patients before initiating ERT.
Main Methods:
- Studied 12 hemizygous males with classic Fabry disease and 15 controls.
- Measured plasma homocysteine concentrations and multiple endothelial factors.
- Evaluated baseline marker levels prior to ERT initiation.
Main Results:
- Patients with Fabry disease showed significantly higher plasma homocysteine levels compared to controls (p < 0.01).
- Plasma vascular cell adhesion molecule-1 was also significantly elevated in patients (p < 0.05).
- A trend towards decreased endothelin-1 levels was observed; other markers showed no significant differences.
Conclusions:
- Endothelial and leukocyte activation markers did not prove reliable for routine ERT monitoring in Fabry disease.
- Hyperhomocysteinemia in Fabry disease requires further study regarding its origins and clinical impact.
- Folic acid or multivitamin therapy may be beneficial for managing the vascular risk associated with hyperhomocysteinemia in these patients.
Aim:
Fabry disease is an X-linked inborn error of glycosphingolipid metabolism due to the deficient activity of alpha-galactosidase A, a lysosomal enzyme. It is a multisystem disorder characterized by progressive renal insufficiency, with added morbidity from cardio- and cerebrovascular involvement. The recent availability of genetically engineered enzyme offers an effective targeted treatment approach, but also emphasizes the need for surrogate markers to delineate organ damage and monitor the efficacy of enzyme replacement therapy (ERT).
Methods:
Multiple endothelial factors and plasma homocysteine concentrations were investigated in 12 consecutive hemizygous males with classic Fabry disease and 15 controls as part of an exhaustive baseline evaluation prior to ERT.
Results:
Compared with the controls, plasma concentrations of homocysteine were significantly (p < 0.01) higher in patients with Fabry disease in the absence of chronic renal failure or vitamin deficiency. Plasma concentrations of vascular cell adhesion molecule-1 were also significantly (p < 0.05) higher in the patients, and there was a trend for decreased endothelin-1 levels. No difference was found in serum intercellular adhesion molecule-1, plasma P-selectin, serum E-selectin and plasma thrombomodulin between the patients and controls.
Conclusions:
The results do not reveal measurable evidence for endothelial and leukocyte activation that could reliably serve as surrogate markers for routine monitoring of the efficacy of ERT in patients with Fabry disease. While the exact origin and clinical significance of hyperhomocysteinaemia in Fabry disease remains to be studied in a larger cohort of patients carefully monitored for their concurrent medications, especially carbamazepine, we suggest that patients may benefit from folic acid or multivitamin therapy to treat this additional vascular risk factor, when present.