DENERVATION OF ECCRINE GLANDS IN PATIENTS WITH FAMILIAL AMYLOIDOTIC POLYNEUROPATHY TYPE-I

Objective: To study the alterations in the structure and innervation o f eccrine glands in familial amyloidotic polyneuropathy (FAP) type I w ith Val 30 Met transthyretin mutation. Background: Anhidrosis of the d istal lower limbs is a prominent feature of FAP type I. Methods: Quali tative and morphometric study of amyloid deposition, eccrine glands, a nd their innervation in nine patients with FAP type I (duration of sen sory symptoms, 8.4 +/- 3.9 years [mean +/- SD]; range, 3 to 15 years) and seven control subjects. Results: On light microscopy, the endoneur ium of cutaneous nerve fascicles had no definite amyloid deposition. A myloid deposition was observed around eccrine glands in seven of nine patients. On electron microscopy, no focal destruction and degeneratio n of eccrine glands or ducts and of Schwann cell processes with or wit hout nerve terminals or unmyelinated axons were observed in relation t o adjacent amyloid deposition. Secretory vacuoles and granules of dark cells were markedly decreased in some secretory coils. Nerve terminal s and unmyelinated axons of eccrine glands were considerably fewer in patients than in control subjects, and denervation was prominent in al l patients. A few nerve terminals and unmyelinated axons of eccrine gl ands were present in patients who had experienced sensory symptoms for 3, 5, and 6 years, but were absent in patients with sensory symptoms for more than 7 years. Conclusions: Eccrine glands are markedly to tot ally denervated in patients with FAP type I and chronic sensory sympto ms. The extent of denervation indicates the severity of autonomic dene rvation and therefore may suggest the timing of liver transplantation.