Health-related quality of life in Norwegian adults with Fabry disease: Disease severity, pain, fatigue and psychological distress.

Health-related quality of life (HRQOL) is reduced in Fabry disease (FD) and associated with clinical disease manifestations, but few have used Fabry-specific severity scores to study how disease burden interferes with quality of life. We investigated how the Fabry DS3, consisting of four somatic domains and one patient-reported item, associates with HRQOL, while also evaluating fatigue, pain and psychological distress as possible predictors. Thirty-six adults with FD completed the Short-form Health Survey (SF-36), the hospital anxiety and depression scale (HADS), the brief pain inventory (BPI) and reported fatigue on a visual analog scale. Clinical data were collected from the last multidisciplinary hospital visit. Using correlation and hierarchical linear regression analyses, we examined associations between demographic, clinical and self-reported predictors and the SF-36 physical (PCS) and mental (MCS) component summary scores. Males scored lower than the general population in all SF-36 domains (P < .05). General health and social functioning were reduced in females. Before including self-reported symptom scores, DS3 showed associations with PCS (P = .009). Our fully adjusted model explained 66% of the variation in PCS, where education (P = .040) and fatigue (P = .002) retained significance. With HADS depression score (P = .001) as the sole significant factor, our regression model explained 56% of the variation in MCS. The DS3 score has implications for HRQOL in FD. Low education and fatigue represent major barriers to physical well-being, while depression strongly influences mental quality of life. Fatigue should be recognized as an important endpoint in future FD trials. Increased efforts to diagnose and treat affective disorders are warranted.

The impact of demographic and clinical characteristics on the trajectories of health-related quality of life among patients with Fabry disease.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by multiorgan dysfunction. Since individuals with FD usually experience progressive clinical disease manifestations, their health-related quality of life (HRQOL) is expected to change over time. However, there is limited longitudinal research examining HRQOL outcomes in individuals with FD. We aimed to: assess longitudinal outcomes in HRQOL in adults with FD; examine the physical- and mental HRQOL trajectories at the initial registration (baseline), 3-5 year, and 7-13 year follow-ups; and evaluate the possible associations of age, sex and medical complications with the physical- and mental HRQOL trajectories. METHODS: Forty-three individuals with FD (53% female) who were aged 18 to 81 years at baseline attended clinical follow-up visits between 2006 and 2020. Medical records were extracted retrospectively. Demographics and the 36-item Short-Form Health Survey (SF-36) were recorded at scheduled visits, except for the last data collection which was prospectively obtained in 2020. The physical (PCS) and mental (MCS) composite scores (SF-36) were chosen as outcome measures. RESULTS: The eight SF-36 domain scores were stable over a span of 13 years, and only physical- and social functioning domains worsened clinically over this follow-up period. Mean baseline SF-36 domain scores were all significantly lower (decreased HRQOL) in the FD sample compared with Norwegian population norms. Two hierarchical linear models were run to examine whether demographics and medical complications (measured at the last clinical visit) predicted physical and mental HRQOL trajectories. Age above 47 years (p < 0.001), male sex (p = 0.027), small fibre neuropathy (p < 0.001), renal dysfunction (p < 0.001), and cerebrovascular events (p = 0.003) were associated with lower HRQOL over time. No significant interactions were found between the time of follow up and the abovementioned predictors of HRQOL. CONCLUSIONS: Overall HRQOL trajectories remained stable between baseline, 3-5 year, and 7-13 year follow-ups, with the majority of individuals reporting decreased physical and mental HRQOL. Medical complications in combination with older age and male sex are important predictors of lower HRQOL in FD. Awareness of this relationship is valuable both for health care providers and for patients. The findings provide indicators that can guide treatment decisions to improve physical and mental HRQOL outcomes.

Life expectancy and cause of death in individuals with haemophilia A and B in Norway, 1986-2018.

OBJECTIVES: Evaluate trends over time in age- and cause of death in males with haemophilia (PWH) in Norway compared with the general male population and investigate its correlates with improvements in haemophilia treatment. METHODS: Data about age and cause of death in the period of 1986-2018, from two independent, high-quality national registries: the Norwegian Cause of Death Registry (NCoDR) and the patient registry at Centre for Rare Disorders (CRD), Oslo University Hospital. RESULTS: Life expectancy increased significantly from 1986 to 2018. However, PWH still had a decreased mean age at death of 56.8 years (SD = 24.7) in the NCoDR and 58.6 years (SD = 21.7) in the CRD data, compared with 73.9 years (SD = 16.3) in the general male population. There was a distinct shift in the most frequently reported haemophilia-related causes of death, such as haemorrhage and AIDS, to more age-related causes of death, such as cancer, reflecting an ageing population. CONCLUSION: Haemophilia treatment has improved significantly in the last three decades. Despite treatment-related improvements, PWH in Norway still have a decreased life expectancy compared with the general male population.

Age at Death and Causes of Death in Patients with Huntington Disease in Norway in 1986-2015.

BACKGROUND: The literature offers discrepant findings regarding age at death in individuals with Huntington disease (HD). OBJECTIVE: To study the age at death and causes of death in males and females with a diagnosis of HD in Norway. METHODS: Registry study of deaths in 1986-2015 using data from two national registries: the Norwegian Cause of Death Registry (NCDR) and the registry of the Centre for Rare Disorders (CRD), Oslo University Hospital. RESULTS: Mean age at death for individuals with HD was found to be 63.9 years (NCDR) and 61.7 years (CRD), compared to a mean of 76.9 years in the general population (NCDR). There were no significant gender differences for age at death in individuals with HD. The significant increase in age at death within the general population from 1986 to 2015 was not observed in individuals with HD. In 73.5% of individuals with HD, the underlying cause of death was HD, followed by cardiovascular diseases, cancer and respiratory diseases. The most common immediate cause of death was respiratory diseases (44.2%). Suicide was a more common cause of death in the population with HD (2.3%) compared to the general population (1.3%). CONCLUSION: The age at death of individuals with HD was stable over a period of 30 years and 13.3 years lower than in the general population. Longer life expectancy for females from the general population was not found in females with HD. Suicide was more common among individuals with HD compared to the general population.