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

Abstract

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.

Keywords

• Fabry disease
• Patient-reported outcomes
• Depression
• Sleep disturbances
• Disability
• Quality of life