Fabry disease can affect the entire nervous system. The main impact of central nervous system alterations in patients with Fabry disease is pathological changes to the blood supply to the brain. This results in an increased incidence of stroke and transient ischaemic attacks.1,2 Stroke occurring at a young age is a serious and common complication in both male and female patients. Fabry disease must be considered in all cases of stroke in individuals below 55 years of age.3,4
Fabry disease can affect the function of blood vessels supplying the brain, resulting in increased regional cerebral blood flow.1 White matter lesions are an early and prominent finding in Fabry disease and are well-described in the literature.5,6 A further common neurological symptom of Fabry disease is tortuous and dilated large blood vessels.5,7
(a) Left cerebellar hemisphere stroke
(b) Left middle cerebral artery stroke
(c) Occlusion of the left vertebral artery
(d) Dilation of the carotid arteries
The peripheral neuropathy of Fabry disease manifests as neuropathic pain and reduced thermal sensation. Alterations in the functioning of the autonomic nervous system can cause hypohydrosis or hyperhidrosis, and affect the gastrointestinal system.1,8 All of these effects have a significant impact on patient quality of life.
Neuropathic pain is considered the clinical hallmark of Fabry disease and is recognized as the most severe and debilitating symptom.9 It is an early symptom and has been reported in pediatric patients as young as 3 years (boys) and 6 years (girls).10 Neuropathic pain typically presents as acroparesthesia,10 which may be chronic, or may occur as episodic, agonising crises known as Fabry crises.11 It has been reported in approximately 77% of male patients (adults and children; n=93) and 70% of female patients (adults only; n=60).9,12
The pain is often described by patients as an excruciating burning sensation in the palms of the hands and the soles of the feet, frequently radiating to the proximal extremities and occasionally to the abdomen.11 Fabry crises may be triggered by hot weather, physical exercise, stress, alcohol intake or high temperature (although the pain itself can cause fever).9,11 The degeneration of nerve fibres in the dorsal root ganglion and of associated small fibres in pathways transmitting pain signals12 is thought to be the cause of the pain.