Depression, sleep disturbances, pain, disability and quality of LIFE in Brazilian Fabry disease patients

Background: Fabry disease (FD) is a lysosomal disease in which mutations affect the GLA gene located on the X chromosome. The defective product, the enzyme alpha-galactosidase A, causes accumulation of substrate and contributes to the disruption of cell function in several organs, with variable severity and consequent damage of tissue or organ function. Patient reported outcomes (PROs) enable patients to provide information regarding the consequences of their disease and its treatment and are often recognized as the most important outcomes for them. Objectives: To evaluate pain, depression, sleep disturbances, disability and disease impact on quality of life in a cohort of Brazilian FD patients and compare between groups stratified by the Mainz Symptom Severity Index (MSSI) Methods: Thirty-seven genotype confirmed classic FD patients - 16 male and 21 female - (mutations: C142R, A156D, L180F, R227X, W262X, G271A, P293S, Y264SX) were evaluated and answered the following questionnaires: Brief Pain Inventory (BPI), Hamilton Depression Rating Scale (HAM-D), Pittsburgh Sleep Quality Index (PSQI), Health Assessment Questionnaire Disability Index (HAQ-DI), Short-Form Health Survey 36 (SF-36). Results: In FD patients, mean +/- SD BPI severity result was 2.78 +/- 2.66 for severe; 2.80 +/- 2.55 for moderate and 1.55 +/- 2.38 for mild severity patients. Mean +/- SD BPI interference result was 2.55 +/- 2.44 for severe; 2.80 +/- 3.18 for moderate and 1.36 +/- 2.83 for mild patients. BPI severity and interference values correlated with MSSI scores (r = 0.24; p < .001 / r = 0.25; p < .001). Application of HAM-D indicated depression in 21 patients (56.8%). HAM-D results had positive correlation with MSSI values (r = 0.21; p < .001), with BPI severity (r = 0.54; p < .001) and interference (r = 0.65; p < .001). PSQI depicted sleep disturbances in 22 patients (59.5%). PSQI values correlated with MSSI values (r = 0.25; p < .001), with HAM-D results (r = 0.65; p < .001) and BPI severity (r = 0.47; p < .001) and interference (r = 0.66; p < .001). Mean HAQ-DI result was 0.490 for severe; 0.274 for moderate and 0.157 for mild severity patients. Conclusions: Depression, sleep disturbances and disability were under-recognized in FD patients. HAQ-DI revealed worse disability according to MSSI severity status. The lowest raw scores from the SF-36 questionnaire were for the domains general health perception and physical role functioning. Standardized assessments should be routine care and started as early as diagnosis of Fabry disease is made.