Lower limb cold exposure induces pain and prolonged small fiber dysfunction in Fabry patients

In Fabry disease, an X-linked alpha-galactosidase A deficiency, painful cri ses and limb paresthesias are possibly linked to thermal exposure. Small ne rve fiber function has not yet been tested after cold challenge. In two Fab ry patients (15 and 17 years old), their heterozygote mother, their healthy sister,:and eight controls, we determined warm and cold perception thresho lds at the dorsal foot and the lower medial calf (method of limits, Somedic -Thermotest (TM)), before and 1, 5, 10 and 15 min after 30 s immersion of o ne leg into 5 degrees C water. Discomfort was rated from 0 to 10. At baseli ne, thermal thresholds of all participants were normal. In contrast to cont rols, the patients tolerated 30 s cold stimulation only with interruptions. The mother aborted stimulation after 6 s because of pain. The patients and their mother reported intense burning pain and numbness during: and after stimulation. After cold exposure, thermal sensation was highly abnormal for 20 min in one and 80 min in the other brother. In controls, thermal thresh olds were somewhat elevated after stimulation but normalized within 10.0 +/ - 4.6 min. Discomfort during cold exposure was rated 8-10 by the patients a nd their mother, but 3-5 by the healthy persons. We assume that glycolipid accumulation in cutaneous and vasa nervorum vesse ls as well as small nerve axone accounts for skin and small fiber malperfus ion during cold induced vasoconstriction. Transitory ischemia initiated bur ning pain and prolonged small fiber dysfunction. (C) 2000 international Ass ociation for the Study of Pain. Published by Elsevier Science B.V.