Patient-Reported Outcomes in Subjects With A143T and R118C GLA Gene Variants

Abstract

Background: Fabry disease (FD) is caused by pathogenic variants in the GLA gene. A143T and R118C variants are considered not disease causing. Patient-reported outcomes provide information concerning the effects of their disease but should be carefully analyzed in rare diseases. Objectives: To evaluate pain, depression, sleep disturbances, disability and quality of life in A143T or R118C Brazilian subjects and compare to data published for classic FD patients. Methods: Nineteen subjects – 8:11 male:female – were evaluated and answered the questionnaires: Brief Pain Inventory (BPI), Hamilton Depression Rating Scale, Pittsburgh Sleep Quality Index, Health Assessment Questionnaire Disability Index (HAQ-DI), Short-Form Health Survey 36 (SF-36). Lyso-Gb3 and residual enzyme activity were obtained. Results: Alpha-galactosidase A activity was low in males. Lyso-Gb3 levels were normal in all subjects. Comparing A143T/R118C subjects and FD patients, BPI severity, BPI interference, HAQ-DI values were not different (p>0.05) whereas raw scores for physical functioning (p=0.01) and general health perception (p<0.01) favored A143T/R118C. Depression and sleep disturbances were similar between groups. Conclusions: A143T/R188C subjects had normal lyso-Gb3 levels. Depression, sleep disturbances and disability were frequent and under-recognized. However, findings depicted in this study are nonspecific and should not be considered as ground for diagnosing Fabry disease.