Published in 2015, results from a systematic review of 54 articles suggested that patients with Fabry disease reportedly have a lower quality of life compared with the general population.1 In a retrospective cohort study of 286 adults, quality of life was reportedly reduced in both male and female patients with Fabry disease, particularly in older males with the classical disease phenotype. Patients with multiple disease manifestations who experienced pain, cardiovascular complications, stroke or transient ischaemic attacks are also more likely to have a reduced quality of life.2

Quality of life in paediatric patients with Fabry disease
The disease manifestations of Fabry disease in children typically involve ≥1 organ, leading to a wide range of possible psychosocial deficits. A study of 24 children with Fabry disease (males, n=10; females, n=14) aged 6‒18 years, and their parents, determined quality of life, psychosocial functioning and depression in patients compared with an unaffected normative cohort. The mean (standard deviation [SD]) age of enrolled patients was 12.0 (3.2) years.3 The unaffected normative cohort included 963 children aged 5‒18 years and 1629 parents of children aged 2‒18 years from paediatric healthcare settings.3,4 The most commonly reported Fabry disease symptoms in this paediatric cohort, as supported by parents (n=21) are presented in Figure 1.3

Figure 1.
Most commonly reported Fabry disease symptoms, as supported by parents. Reproduced with permission from Bugescu N et al. J Pediatr Genet 2016; 5: 141-149.3,5,6

Paediatric patients with Fabry disease reported significantly lower quality-of-life scores compared with the normative cohort in many domains, including total score (p=0.005), physical health (p=0.003), psychosocial health summary (p=0.01), social functioning (p=0.026) and school functioning (p=0.011). Parental reports of reduced quality of life in their child with Fabry disease were similar. Assessment of psychosocial functioning was determined in two age cohorts: younger children (aged 6‒11 years; n=12) and adolescents (aged 12‒16 years; n=14). Parents of patients in the younger age group did not report any differences in externalising problems, internalising problems, behavioural symptoms or adaptive skills, as compared with the normative cohort (p>0.05). However, parental reports of adolescents with Fabry disease indicated that patients were more likely to have internalising problems (p<0.001), specifically anxiety (p=0.006), depression (p=0.01) and somatisation (p<0.001), behavioural problems (p=0.043), attentional problems (p=0.037) and differences in adaptability skills (p=0.017) compared with the normative cohort. There were no significant differences between paediatric patients’ self-reports of symptoms of depression versus the normative cohort; however, 21% of patients did express clinically depressive symptomatology. The findings from this study indicate that paediatric patients with Fabry disease exhibit lower quality of life compared with those without the disease, and that adolescent patients may be differentially impacted.3

Published in 2008, data on quality of life were available from 36 paediatric patients (aged 14‒18 years) enrolled in the Fabry Registry (sponsored by Sanofi Genzyme), which was initiated in 2001, and is an ongoing, international, multicentre, observational programme for patients with Fabry disease.7,8 Male patients with Fabry disease reported a significantly poorer quality of life compared with males without Fabry disease aged 18‒25 years in the general US population. Males with Fabry disease reported more deficits in physical functioning, physical role, body pain, general health, vitality, social functioning and mental health. Compared with females without Fabry disease aged 18‒25 years in the general US population, female patients with Fabry disease exhibited significantly poorer quality of life, specifically in terms of body pain and general health. These results suggest that paediatric patients with Fabry disease exhibit impairments in quality of life, which may represent an immediate disease burden.7

Quality of life in adult patients with Fabry disease
An international survey aimed to investigate the impact of Fabry disease-specific pain and gastrointestinal symptoms on quality of life in 367 adult patients (males, n=120; females, n=245). The majority of patients (53.1%) were aged 41‒60 years; the remaining patients were aged 18‒40 years (34.3%) and 61‒80 years (12.5%). Most patients (87.2%) had been diagnosed with Fabry disease for >24 months at the time of study participation. More than half of the patients (54.2%; 199/367) reported frequent pain specific to Fabry disease; 60.8% of patients (223/367) indicated that pain was associated with their hands, feet and abdomen. For patients who experienced pain, this impacted daily activities, overall mood, walking ability, normal work activities, relations with other people, sleep patterns and enjoyment of life. For patients who experienced moderate or severe pain, this was more likely to moderately or severely interfere with quality of life. Frequent diarrhoea was reported by 39.2% of male patients (47/120) and 23.3% of female patients (57/245). Assessment of gastrointestinal symptoms and disease-specific pain showed that 25.3% of patients (93/367) with moderate-to-severe pain frequently had diarrhoea. Results from this study highlight that pain can significantly impact daily activities and quality of life in patients with Fabry disease.9

In a separate study, pain, depression, sleep disturbances, disability and disease impact on quality of life was evaluated in 37 adult Brazilian patients with classical Fabry disease (males, n=16; females, n=21). The mean (SD) age of enrolled patients was 43.1 (15.4) years.10

  • 59.5% of patients (n=22) used over-the-counter pain medication.10
  • 56.8% of patients (n=21) had depressive symptoms, of whom five had severe depression.10
  • 59.5% of patients (n=22) reported sleep disturbances.10
  • 45.9% of patients (n=17) had insomnia and/or unrefreshing sleep.10

Only one female patient reported mild disability associated with chronic pain, but no kidney, heart or central nervous system damage or arthritis. Quality of life was measured using the Short-Form Health Survey 36 (SF-36), where lower scores indicated greater disability (possible range, 0‒100). The lowest mean (SD) score was for general health perceptions (48.89 [21.3]) in patients with Fabry disease, followed by physical role functioning (51.35 [39.40]). Mean (SD) perceptions of general health were poorer for male (39.1 [17.1]) vs female (56.4 [20.7]) patients (p=0.01). Data from this study suggest that depression, sleep disturbances and disability may be under-recognised in patients with Fabry disease, and may impact quality of life.10

An additional study aimed to assess the impact of growing up with Fabry disease in 28 Dutch young adults (males, n=9; females, n=19) aged 18‒35 years, and current quality of life. Acroparaesthesia was present during childhood for all male patients (100%) and 11 female patients (58%). In both males and females, a proportion of patients also experienced angiokeratomas (22% and 21%), anhidrosis or hypohidrosis (22% and 16%), and abdominal pain (33% and 26%), respectively. The median age at diagnosis was 17 years for both males (range, 9‒35 years) and females (range, 13‒21 years). However, median age at onset of symptoms was earlier in male versus female patients (7.5 vs 9 years).11

Compared with the normative control group (485 individuals without Fabry disease aged 18‒30 years from the general Dutch population), there were no differences in sociodemographic outcomes, autonomy development and psychosexual development. These milestones included: regular chores in the family; paid jobs; vacation without adults; leaving the parents’ home; first partner; falling in love; first-time sexual intimacy; and first-time sexual intercourse. However, male patients with Fabry disease achieved fewer milestones in social development compared with males from the normative control group. There were no differences in social development between female patients with Fabry disease and females from the normative control group.11

The findings from this study suggest that both males and females with Fabry disease appear to achieve normal psychosocial development until adulthood. In some domains, quality of life was also reduced in male and female patients with Fabry disease, particularly general health perception.11

Experiences of 10 females with Fabry disease from Norway
A qualitative study of 10 Norwegian female patients with Fabry disease aged 24‒77 years (mean age, 54 years) was performed to gather insight into living with the disease. Seven out of 10 patients experienced symptoms of Fabry disease. Of the eight patients who had children, five had children also diagnosed with the disease. For the three remaining patients with children, the children of one patient had not been tested and for the other two patients, their children had been tested but did not have Fabry disease. Three main themes were identified during the study: learning about being heterozygous for Fabry disease; coping with Fabry disease; and experiences with follow-up and treatment.12


Learning about being heterozygous for Fabry disease
Many patients had learned about their diagnosis in adulthood as a result of a male relative or child having been diagnosed with Fabry disease. For many patients, they reported not being understood or not having their symptoms taken seriously by clinicians; therefore, for some patients, receiving a diagnosis of Fabry disease was a relief because it provided an explanation for their previously unexplained symptoms. Most patients described challenges in communicating the genetic disorder to family members, although they acknowledged that they felt it was important to be open about the disease to their children. However, for some patients, their children did not want to discuss Fabry disease due to social stigma. Some patients also expressed guilt of having passed on a “faulty gene” to their children and grandchildren. However, other patients acknowledged that there was nothing they could have done to prevent this.12

Coping with Fabry disease
Distinguishing between Fabry disease and daily life was important for all patients included in the study. For some female patients, they felt that regular clinical appointments interfered with their daily life, and many did not want their work colleagues to know of their disease. It was also important for patients’ social life and social identity to be separated from Fabry disease.12

Experiences with follow-up and treatment
Although grateful to receive treatment, some patients indicated that hospital appointments, making plans to receive medication from the pharmacy, planning treatment time, and taking absences from school or work was time-consuming. Patients also expressed deep frustration regarding the lack of knowledge of Fabry disease among healthcare providers. The patients stated that this made them feel insecure, misunderstood, afraid and sometimes angry.12

The results from this study of 10 Norwegian female patients with Fabry disease highlighted they had different feelings towards their diagnosis, and healthcare providers should personalise information, support and management of Fabry disease.12

 

C-ANPROM/INT/FAB/0015; Date of preparation: March 2021