Depression: The Hidden Problem in Fabry Disease. A Review

Abstract

Fabry disease (FD) is an X-linked disorder of glycosphingolipids caused by mutations of the GLA gene. The classical form presents with neuropathic pain and gastrointestinal complaints since childhood or adolescence and progressing into adulthood with ischemic stroke, cardiac dysfunction, and chronic kidney disease. Depression seems to be a frequent complication of FD but its frequently underdiagnosed and undertreated. Comorbid depression in different chronic diseases has been associated with an overall increase in disease burden and medical costs, impairment in activities of daily living, and impact on self-care and treatment adherence. In addition, a clear association between pain and depression has been observed in FD patients and appears to have an unequivocal neurobiological matrix. The aim of this review is to provide an overview of the literature on depression in patients with FD and to highlight some of the emerging issues on this topic. Further research to improve detection and to develop effective treatments for depression in this population is promptly needed.

Neuropsychiatric Symptoms and Their Association With Sex, Age, and Enzyme Replacement Therapy in Fabry Disease: A Systematic Review

“…Only few reviews and systematic reviews assessing neuropsychiatric aspects of FD have been published so far ( 42 , 44 – 46 ). They highlighted cognitive impairment in executive functioning, information processing speed, and attention, while other domains, such as general intellectual functioning, memory, naming, perceptual functioning, and global cognitive functioning remained intact.…”

“…They highlighted cognitive impairment in executive functioning, information processing speed, and attention, while other domains, such as general intellectual functioning, memory, naming, perceptual functioning, and global cognitive functioning remained intact. The prevalence of depression varied from 15 to 62%, and neuropathic pain was recognized as a main contributing factor ( 46 ). A review article on depression in FD ( 46 ) highlighted the influence of pain on the depressive symptoms, but questioned the relation between cerebrovascular disease, imaging parameters and depression.…”

“…The prevalence of depression varied from 15 to 62%, and neuropathic pain was recognized as a main contributing factor ( 46 ). A review article on depression in FD ( 46 ) highlighted the influence of pain on the depressive symptoms, but questioned the relation between cerebrovascular disease, imaging parameters and depression. To our best knowledge there is no review article highlighting impact of sex, age or ERT status on NPS in FD.…”

“…Comprehensive treatment plans should consider therapies to improve occupational and psychological functioning, which could lead to improved treatment compliance, daily functioning, and better quality of life and showed to be effective in depression ( 57 ). Considered a great impact of pain in depressed FD individuals, a certain antidepressant, such as the dual serotonin and noradrenaline reuptake inhibitors, targeting both depression and pain, are of interest and may allow treating both disorders with a single medication ( 46 ). Finally, of special interest is the assessment of ERT impact on NPS.…”

Updated Evaluation of Agalsidase Alfa Enzyme Replacement Therapy for Patients with Fabry Disease: Insights from Real-World Data

“…Considering that depression is a frequent finding in patients with FD and is associated with chronic neuropathic pain, dual antidepressants like duloxetine or venlafaxine, in our experience, are very useful in these patients with fewer side effects than tricyclics. 92 , 93 …”