ERT may protect heart function after Fabry kidney failure
Treatment stabilized and improved key cardiac measures in 2 men: Case study
Enzyme replacement therapy (ERT) preserved or improved heart function in two men with Fabry disease who had already experienced kidney failure and were undergoing renal replacement (dialysis or kidney transplant), a new case study reports.
The study provides evidence that ERT, the standard treatment for Fabry disease, can still provide benefits to the heart even when the kidneys are severely impaired.
“Patients with Fabry disease who are on renal replacement therapy may benefit from enzyme replacement therapy,” researchers wrote.
Details were published in the Journal of Medical Case Reports, in the study “Adequate hemodialysis does not compromise the cardioprotective effect of agalsidase alfa on patients with Fabry disease: a case report.”
Fabry disease and kidney failure
Fabry disease is a genetic disorder marked by a deficiency in the activity of an enzyme called alpha-galactosidase A, or alpha-Gal A. Without sufficient enzyme activity, metabolites such as globotriaosylceramide (Gb3) accumulate to toxic levels, impairing organ function, particularly in the kidneys and heart.
People with Fabry-related kidney disease often undergo dialysis, a procedure that cleanses the blood by removing waste products, mimicking the kidneys’ filtration process. In more severe cases, a kidney transplant is required.
However, whether ERT helps protect the heart in Fabry patients who undergo renal replacement therapy remains unclear.
To address this, a research team in China assessed changes in the heart structure and function of two Han Chinese men with Fabry after 18 months of ERT.
Case 1: kidney transplant and delayed ERT
In the first case, the man had experienced inadequate sweating (hypohidrosis) and episodes of tingling, numbness, or prickling sensations in the extremities (acroparesthesias) since he was 5 years old. At 19, he was diagnosed with uremia, a buildup of waste products in the blood and a sign of impaired kidney function. As such, he began dialysis, which was maintained for nearly three years. Eventually, he underwent a kidney transplant.
Tests revealed low levels of alpha-Gal A activity in white blood cells and high levels of lyso-Gb3, a metabolite of Gb3, in his blood. At 24, he was diagnosed with Fabry disease after genetic analysis revealed he had mutations in the GLA gene, which encodes alpha-Gal A.
Due to financial constraints, he began ERT with agalsidase alfa (sold as Replagal) at age 27, which led to a drop in blood lyso-Gb3 levels after three months of treatment, although still above the normal range.
During follow-up, no significant changes were detected in cardiac structure or function. He had no signs of chest pain, shortness of breath, or lower limb swelling. His exercise capacity was in the normal range, as assessed by the distance walked in six minutes.
After ERT, an ultrasound confirmed that the thickening of his heart muscle (myocardial hypertrophy) and enlarged heart chambers remained stable. However, the treatment did improve his heart function: a key measure of the upper chamber’s health, the left atrial reservoir strain, significantly improved from 29.4% to 53.1%, “representing a significant and promising change,” the team wrote.
An electrocardiogram (ECG) also showed improvements in the PR interval, the time between electrical activity that starts in the atria (the heart’s upper chambers) and the beginning of ventricular contraction and the heartbeat.
Case 2: end-stage kidney disease and ongoing dialysis
Similar to the first case, the second man was unable to sweat from age 9. By 28, he was diagnosed with nephrotic syndrome, a sign of kidney damage, which was confirmed by biopsy. His condition progressed to end-stage kidney disease with uremia by age 30, requiring ongoing dialysis three times a week.
His ECG also showed an incomplete right bundle branch block (IRBBB), a delay or blockage in the pathway through which electrical impulses travel to make the heart beat.
At 32, he underwent genetic screening which revealed a mutation in the GLA gene, confirming the diagnosis of Fabry disease. He began ERT, leading to a drop in blood lyso-Gb3 levels after three months of treatment.
During the follow-up, he had no chest pain, shortness of breath, or lower limb swelling, and blood levels of troponin I, a marker of heart damage, remained within the normal range. In contrast, the levels of B-type natriuretic peptide, a marker of heart failure, fluctuated, “suggesting a slight possibility of heart failure onset,” the team noted.
Although he was unable to participate in the six-minute walk test due to leg bone degeneration, the PR interval was within the normal range. He continued to exhibit IRBBB and experienced sinus bradycardia, a heart rhythm where the heart beats slower than expected, which improved after ERT. Echocardiogram revealed myocardial hypertrophy and an enlarged left atrium. ERT improved his left atrial reservoir function from 46.3% to 59.3%.
“The improvements in myocardial [electrical] activity and left atrial reservoir function seen in this study indicate clinical benefits of ERT for patients with [Fabry], even in those experiencing renal failure,” the researchers concluded.
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