Fabry can pose serious heart risk for women, men
Study in Finland urges diligent cardiac monitoring for male, female patients
Fabry disease takes a significant toll on the hearts of both male and female patients in Finland, often leading to cardiomyopathy, a serious heart condition, according to a recent study. This condition, which weakens the heart muscle, increases the risk of heart failure and stroke.
Researchers also found a difference between the sexes: cardiomyopathy tends to develop earlier in men, and it is also linked to a younger age at death.
“In Finnish Fabry patients, the genetic background is diverse. Cardiomyopathy is very common not only in men but also in women,” researchers wrote.
The study, “Genetics, cardiac phenotype and cardiovascular outcomes in Fabry disease patients in Finland,” was published in ESC Heart Failure.
Fabry disease is caused by mutations in the GLA gene that result in a deficiency of an enzyme called alpha-galactosidase A. Without this enzyme, fatty molecules build up to toxic levels in cells, causing damage to organs such as the heart and the kidneys.
Finnish population: Distinct hereditary diseases, unique genetic makeup
Because of the unique genetic makeup of the Finnish population and the presence of distinct hereditary diseases, researchers conducted a study to examine the genetics, clinical profiles, and cardiovascular outcomes of patients in the country’s registry of Fabry disease (NCT00196742). The study was partially sponsored by Sanofi, which markets an approved treatment for Fabry disease called Fabrazyme (agalsidase beta).
Since cardiac complications are the leading cause of death in those with Fabry, the team’s primary focus was on Fabry cardiomyopathy and its natural progression. The study included 97 patients (32 male and 65 female), including six children and adolescents, who were followed for an average of 12 years. They were diagnosed with Fabry disease at an average age of 37, with male patients being diagnosed an average of 12 years earlier (29 vs. 41 years).
Most patients had symptoms, with many experiencing nerve pain, skin lesions, and digestive problems. Kidney problems were common, with many patients showing high levels of protein in their urine. Three men developed end-stage kidney disease and needed a transplant.
More than half of the male patients (59%) had classic Fabry disease, 31% had a late-onset form, and 9% had an intermediate form. Most women (95%) had symptoms, which is different from earlier research that suggests many women with Fabry disease may be asymptomatic.
Most men (88%) and more than half of the women (57%) received enzyme replacement therapy. A smaller number used Galafold (migalastat), a chaperone therapy.
Cardiomyopathy found in 66% of men, 49% of women in study
The researchers identified 22 different genetic mutations in 26 families in the study. Cardiomyopathy developed in 66% of men starting in their 20s and in 49% of women starting in their 40s. The condition was diagnosed using a type of heart scan called cardiac magnetic resonance (CMR), which showed signs like thickened heart walls, abnormal heart tissue, and changes in heart structure. The team noted that, in a woman with a particular mutation called p.T410A, certain heart abnormalities showed that Fabry cardiomyopathy had likely been present since her 30s.
Among the 53 patients with cardiomyopathy, about 30% developed atrial fibrillation (an irregular heartbeat); 32% stroke; 26% heart failure (when the heart can’t pump blood properly); and 6% end-stage kidney disease.
A technique used in cardiac MRI to detect scarring or permanent damage in the heart muscle showed that lasting heart damage was especially common and severe in women.
Nine patients (six female, three male) died during the study — three from heart failure and three from stroke. The average age of death was 48 years for the men and 75 for the women. Eight of the nine patients who died had cardiomyopathy, showing that heart problems in Fabry disease can significantly shorten life expectancy in both men and women.
“Our findings highlight the need for even more diligent monitoring of cardiac manifestations also in females with [Fabry disease] by regular cardiac imaging with CMR,” the researchers concluded.
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