Awareness of Fabry disease among rheumatologists--current status and perspectives

Clin Rheumatol. 2011 Apr;30(4):467-75. doi: 10.1007/s10067-010-1445-z.


Fabry disease is an inherited disorder of lipid metabolism caused by deficient activity of the lysosomal enzyme α-galactosidase A. Burning peripheral pain with triggered crises of excruciating pain and gastrointestinal dysmotility point to Fabry small fiber neuropathy; angiokeratoma, corneal deposits, and hypohidrosis are other common early manifestations. Progressive dysfunction of the kidneys, heart, and/or brain develops in adulthood. Diagnosis is often delayed which is of great concern, as therapeutic outcomes with enzyme replacement therapy are generally more favorable in early stages of Fabry disease. Results of a survey among 360 rheumatologists and pediatricians clinically managing patients with rheumatologic conditions demonstrate that Fabry manifestations are generally poorly recognized and that awareness of appropriate diagnostic tests is low. To raise awareness about the musculoskeletal aspects of Fabry disease among rheumatologists, the International Musculoskeletal Working Group on Lysosomal Storage Disorders has reviewed the current knowledge. We propose a diagnostic algorithm with burning pain in hands and feet and triggered attacks of excruciating pain as keystones. Evidence of autonomic nerve dysfunction and simple temperature sensitivity testing can provide important diagnostic clues. Multi-systemic involvement should be explored by taking a detailed medical history, including family history, and performing a thorough physical examination and appropriate laboratory workup. Confirmatory tests include the α-Gal A enzyme activity assay (males) and genetic testing (females). We propose that medical specialists use our diagnostic algorithm when evaluating individuals with peripheral neuropathic pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthralgia / etiology
  • Data Collection
  • Enzyme Replacement Therapy
  • Fabry Disease / diagnosis*
  • Fabry Disease / therapy
  • Female
  • Health Knowledge, Attitudes, Practice*
  • Humans
  • Male
  • Peripheral Nervous System Diseases / etiology
  • Practice Patterns, Physicians'*
  • Rheumatology*