The study, “Clinical profile of women diagnosed with Fabry disease non recipient enzyme replacement therapy,” was published in the journal Medicina Clínica.
This was the first epidemiological study conducted in Spain to characterize the clinical profile and health conditions of women with Fabry disease who are not receiving enzyme replacement therapy.
“Although women were historically considered only carriers, many studies have contradicted this fact,” researchers said. It is uncertain whether women carrying the disease need ERT.
The classic assumption is that Fabry disease does not affect females as much as males because it is an X-linked disorder. Because females have two X chromosomes (males have only one), a gene that is defective in one chromosome — in this case the GLA gene — can be compensated for by a functional copy of the equivalent gene in the other X chromosome. This usually leads to less severe symptoms, and in rare cases may cause no symptoms at all.
As such, men are much more likely to receive treatment and be enrolled in registries than women. Consequently, there is a lack of data regarding treatment response in women in pivotal ERT studies.
However, there is increasing evidence that “the vast majority of women may experience symptoms related to the disease and in some cases, as severe as in men, but with a later onset of clinical signs or symptoms,” the researchers stated.
The team reviewed clinical records along with a clinical assessment made by a doctor during a study visit, and patient responses to questionnaires addressing health status and symptoms.
There were 33 women (mean age 45.6) enrolled at several specialized centers across Spain.
The data showed that women began to have the first symptoms at a median age of 35.5 years, but were diagnosed a median of two years later.
Six patients received symptomatic treatment, including painkillers and anti-inflammatory drugs, with only one being specific for neuropathic pain (caused by damage to nerve fibers involved in bodily sensations).
Despite most of the women (69%) being considered to have no symptoms, according to the clinical records, 68.8% had at least one symptom.
The most frequent disease-related symptoms were tingling in hands and feet (40.9%), dizziness (27.3%), headache (27.3%), heart palpitations (27.3%), constipation (27.3%), pain in joints (27.3%), back pain (22.7%) and reduced ability to sweat, or hypohidrosis (22.7%).
According to two patient-reported scales — the The Mainz Severity Score Index (MSSI) and the Fabry International Prognostic Index (FIPI) — neurological symptoms were the most severe and those with the worst prognostic.
The health-related quality of life survey EQ-5D showed that 42.2% of the patients had some symptoms of anxiety or depression and 30.3% thought their life was somehow affected by the pain.
Most (62.5%) were not receiving any treatment and ERT was offered to only one patient (3.6%), who refused it.
Among the studied population, missense mutations at the GLA gene were the most common cause of the disease (68.8%). Of note, missense mutations are single nucleotide (the building blocks of DNA) mutations that alter protein composition.
Patients with a deletion in the gene (28.1%) reported worse neuropathy symptoms and pain intensity than those harboring a missense mutation. However, this was was not reflected in the patients’ self-assessed quality of life.
In light of the results, researchers stressed that although most women had not received ERT or other type of treatment, they presented symptoms of the disease.
Researchers noted that despite being diagnosed with Fabry disease, “very few complementary tests were carried out to properly follow up these patients accordingly to current guidelines.”
This observation suggests that monitoring of these women might have been performed inappropriately because of the misconception of seeing women as disease carriers instead of patients.
Therefore, “careful follow-up of female patients or some adjuvant treatment may be considered to delay progressive organ damage and improve patient quality of life,” the researchers concluded.