Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel

Abstract

BackgroundFabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids 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 young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen.MethodsAn international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain.ResultsWe describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e.g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients.ConclusionsOur recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be inadequate.

When arthralgia is not arthritis

“…The most severe manifestations, such as renal and heart failure, and stroke without treatment appear in the third decade of life (1). The pathophysiology of neuropathic pain in FD is associated with the small nerve fiber damage (A delta and C) because of ischemia in the vasa nervorum and the deposit of glycosphingolipids in the dorsal root ganglia (2). Sensory neuropathy is experiences as a burning pain in the hands and feet, which is associated with pain crises during fever episodes and when exercising.…”

The neurological manifestations of Fabry disease. A review

“…Учитывая, что сильная нейропатическая боль, гипо-гидроз, нарушение холодовой перцепции характерны для болезни Фабри, их инструментальное тестирование мо-жет служить для оценки эффективности проводимого ле-чения [78,79]. Для оценки степени выраженности и про-грессирования болезни у взрослых пациентов применя-ются также соответствующие шкалы: Mainz Severity Score Index (MSSI) и Fabry Outcome Survey Mainz Severity Score Index (FOS-MSSI) [80], а также стандартные опросники качества жизни пациентов [81].…”

“…Начиная с 2001 г. проводят фермент-заместительную терапию (ФЗТ) рекомбинантными препаратами α-галактозидазы А [90]. Она позволяет уменьшить нейро-патическую боль [91][92][93][94][95][96][97], улучшить функционирование различных типов нервных волокон иинтрадермальных ре-цепторов вибрации [98], также отмечается улучшение функции потооделения, переносимость жары, темпера-турная чувствительность [99,100].…”

Fabry disease in infancy and early childhood: a systematic literature review

“…These symptoms are probably related to gastrointestinal dysmotility caused by autonomic dysfunction. 36,48 In early childhood reports, gastrointestinal issues were reported in six children 1.0-4.1 years of age. Specific issues included gastrointestinal pain in four children, as well as additional findings that included one or more of diarrhea, constipation, nausea, and vomiting in three children.…”

“…36 Although symptom-specific medications-such as carbamazepine to treat chronic acroparesthesia, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers to reduce levels of proteinuria, and antidepressants-may not typically be needed in early childhood, health-care providers should discuss the use of these medications as needed. 48 Beyond individual exercise and temperature intolerance, there are currently no specific dietary or activity restrictions reported or suggested for patients diagnosed with Fabry disease in early childhood.…”