Small Fiber Neuropathy in Fabry Disease: a Review of Pathophysiology and Treatment

Abstract

Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of glycolipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at a young age. Neuropathic pain and pain attacks are often the presenting symptoms of the disease and start at an average age of 9 years in male patients and 16 years in female patients, but currently a systematic literature review in early childhood showed the presence of these symptoms before the age of 5 years. Clinical studies have shown that enzyme replacement therapy may improve the overall pain scores and pain intensity in patients; improvements in pain outcomes have been sustained during the long-term follow-up, allowing many patients to reduce their use of pain medication. Some indirect evidence from dose-switching studies suggests that enzyme replacement therapy dose may be of relevance to pain outcomes. Considering that damage to small nerve fibers occurs early, prompt treatment is important in order to limit damage to the peripheral nervous system. In this article a comprehensive overview of the existing literature on small nerve fiber pathophysiology and the relationship with neuropathic pain and treatment response in children and adults with Fabry disease is presented.

Ion channels and pain in Fabry disease

“…12 Two types of pain are generally described in FD: the episodic painful crises, also known as ''Fabry crises,'' characterized by agonizing burning pain starting in the extremities and radiating centripetally that may be precipitated by fever, exercise, fatigue, stress, or rapid temperature changes; and the second type is chronic pain characterized by burning and shooting pain in the hands or feet. 13 The definition of the type of pain is highly relevant to classify and decide on the therapeutic approach (see Politei et al 12 and Schuller et al 4 for pain treatment). € Uc¸eyler et al classified FD pain more precisely into 4 types: evoked pain, pain attacks, permanent pain, and pain crises as reported by patients.…”

Variables Associated with Glomerular Hyperfiltration in Fabry Disease Patients

“…CNS compromise was determined by clinical stoke history or asymptomatic lesions on brain magnetic resonance (1). PNS compromise was considered in patients suffering from acroparesthesias or in the presence of alterations in quantitative sensory testing (QST) (10).…”

Corneal Confocal Microscopy and the Nervous System: Introduction to the Special Issue

“…Patients with Fabry’s disease demonstrate small fibre neuropathy as a result of nerve damage induced by globotriaosylceramide (GI 3 ) [ 60 ]. Corneal nerve loss is demonstrated in patients with Fabry disease [ 61 ], which is correlated with disease severity [ 62 ].…”