Family planning is the main event in a woman’s life that’s most affected by Fabry disease, while passing the disease onto her children was the biggest concern, according to a survey of patients and caregivers in Japan.
Most respondents also felt the condition affected their mental health. “This study provides important insights into the experiences of women living with Fabry disease in Japan, emphasizing the multifaceted challenges they face,” the researchers wrote. The survey’s details were published in Molecular Genetics and Metabolism Reports in the study, “Exploring the burdens of women living with Fabry disease in Japan: A patient survey of 62 respondents.”
Fabry disease is caused by mutations in the GLA gene, resulting in a deficiency of the alpha-galactosidase A (alpha-Gal A) enzyme. This results in the progressive accumulation of fatty substances, specifically globotriaosylceramide (Gb3) and lyso-Gb3, particularly in cells that make up the kidneys, heart, and nervous system.
The disease is inherited in an X-linked dominant manner, meaning only one mutated copy of GLA on a single X chromosome is sufficient to cause it. Because males have one X chromosome and one GLA copy, it was thought that they were solely affected and that females were asymptomatic carriers, as the second GLA copy is usually normal. It’s now understood that females with a single mutated GLA gene can develop Fabry disease, characterized by a range of ages of onset, symptoms, and progression, that can sometimes be as severe as in males.
As a result, female patients often face a distinct set of challenges, including a limited knowledge of the disease among healthcare providers, not being able to recognize symptoms, and delays in diagnosis.
Men’s, women’s concerns with Fabry disease
Here, researchers recruited 62 participants, primarily women (75.8%), to complete a 22-question survey to better understand the burden of disease and quality of life in women with Fabry disease in Japan. The questions focused on disease history, symptoms, treatment status, and the challenges faced by women. The work was sponsored by Amicus Therapeutics, which markets Galafold (migalastat), an approved therapy for Fabry.
“This study seeks to inform healthcare providers and researchers about the importance of sex-specific considerations in the management of Fabry disease, ultimately contributing to better health outcomes and improved [quality of life] for affected women,” the researchers wrote.
Nearly all the respondents (82.3%) identified as patients, while some were both patients and caregivers (9.7%) or just caregivers (3.2%). Significantly more men than women were the first member of their family to receive a Fabry diagnosis (57.1% and 16.7%), and the women tended to be older than men at their diagnosis (mean, 37.7 vs. 30.5).
More men were experiencing disease symptoms (92.9% vs. 86.0%), and all the men and 88.4% of the women were receiving treatment, mostly enzyme replacement therapy.
The most common symptoms reported by men were no or reduced sweating (84.6%), hearing impairment (76.9%), and gastrointestinal symptoms (69.2%). Women reported heart-related symptoms (59.5%), pain in the hands or feet (48.6%), no or reduced sweating, and hearing impairment (32.4% each).
Family planning, inheritance guilt
The participants also ranked the impact of Fabry on the key events in a woman’s life — the onset of puberty, menstrual cycle, marriage, family planning, childbirth, perimenopause, menopause, post-menopause, and relationship building. About half (48.4%) the respondents said Fabry disease impacted family planning. Also mentioned was the onset of puberty (17.7%) and the menstrual cycle (12.9 %). Among women, family planning remained the most frequent problem (60.5%) associated with Fabry.
Inheriting the disease and its impact on children were more frequently noted by the female respondents (89.1% vs. 60.0%), while both women and men said women hold these concerns due to prejudice, stigma, and the guilt associated with the disease’s hereditary nature.
“The findings are consistent with previous studies in which women with Fabry disease reported feelings of guilt for passing the disease on to their children, coupled with anxiety or depression, and exacerbated by a sense that they are stigmatized by society,” the researchers wrote.
Most agreed or strongly agreed Fabry disease affects a woman’s mental health, while over half (58.6%) agreed or strongly agreed that patient organizations recognized their challenges. Only about a third (37.9%) agreed or strongly agreed that their primary care physician understood the challenges faced by women, but this increased to nearly half (48.3%) for Fabry specialists.
This finding highlights a “critical need for improvements in patient-physician communication and increased medical education about Fabry disease in Japan,” the researchers wrote.
Less than a third (28.1%) said they agreed or strongly agreed that their family or colleagues understood these challenges, or that women with Fabry received tailored care (26.3%).
“There is a pressing need to provide tailored individual care for women living with Fabry disease and for more efforts to reduce societal prejudice,” the researchers wrote. “By fostering awareness, enhancing communication, and supporting healthcare professionals in their efforts to address both the medical and psychosocial aspects of the disease, we can improve the [quality of life] for these patients.”