Excessive Daytime Sleepiness Is a Common Symptom in Fabry Disease

Abstract

Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by a deficient activity of the enzyme α-galactosidase A, resulting in a vasculopathic involvement of various organ systems, e.g. cerebral structures. Marked cerebral vasculopathy with subsequent white matter lesions (WML) are a frequent finding in FD patients. Recent studies discussed an association between cerebral white matter changes and sleep-related disturbances of breathing, which may lead to excessive daytime sleepiness (EDS). A 56-year-old Caucasian female FD patient with EDS was admitted to our sleep laboratory. Overnight polysomnography showed a Cheyne-Stokes respiration pattern with significant O(2) desaturation. MR imaging revealed confluent WML including the brain stem, but no renal or cardiac involvement. We then evaluated the clinical data of 49 genetically proven FD patients (27 males; mean age 43 years) from our FD centre. With a frequency of 68%, EDS exceeds the prevalence of other common symptoms of FD (angiokeratomas 61%; acroparaesthesia 51%; renal involvement 29%; cardiac involvement 27%), and the prevalence of chronic fatigue (48%). EDS was independently associated with the physical component summary of the SF-36 data (corrected R(2) = -0.323, p < 0.001). EDS and age explained a quarter of variance in mental component summary (corrected R(2) = -0.253, p < 0.001). We conclude that EDS is a common and underdiagnosed symptom in FD patients, accompanied by a significant impact on quality of life. EDS might be caused by central breathing disorders due to an affection of brain regions associated with respiratory control in FD.

Fig. 1

Lower row: T2-weighted (3.0 Tesla; TR 4000/TE 120) sequences of cranial MRI of a FD patient show confluent bilateral white matter changes, significantly involving the brainstem (arrows). Upper row: Polysomnographic detail of the same patient shows a Cheyne-Stokes respiration characterized by oscillation of ventilation between central apnea and hyperpnea with recurring O₂ desaturation.

Fig. 2

Prevalence of symptoms and organ involvement in 49 FD patients. Prevalence of each symptom is expressed as percentage of the total number of patients. Excessive daytime sleepiness was the most common clinical symptom.