Efficacy of exogenous oral zinc in treatment of patients with carbonic anhydrase VI deficiency

Citation
Ri. Henkin et al., Efficacy of exogenous oral zinc in treatment of patients with carbonic anhydrase VI deficiency, AM J MED SC, 318(6), 1999, pp. 392-405
Citations number
171
Language
INGLESE
art.tipo
Article
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Journal title
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
ISSN journal
0002-9629 → ACNP
Volume
318
Issue
6
Year of publication
1999
Pages
392 - 405
Database
ISI
SICI code
0002-9629(199912)318:6<392:EOEOZI>2.0.ZU;2-D
Abstract
Background: We previously described a disorder in 18 patients with decrease d parotid saliva gustin/carbonic anhydrase (CA) VI secretion associated wit h loss of taste (hypogeusia) and smell (hyposmia) and distorted taste (dysg eusia) and smell (dysosmia). Because gustin/CAVI is a zinc-dependent enzyme we instituted a study of treatment with exogenous zinc to attempt to stimu late synthesis/secretion of gustin/CAVI and thereby attempt to correct the symptoms of this disorder. Methods: Fourteen of the 18 patients with this d isorder completed the study. They were treated with 100 mg of exogenous zin c daily for 4 to 6 months, in an open clinical trial. Both before and after treatment, measurements were obtained of parotid saliva gustin/CAVI, parot id saliva, serum and urine zinc, taste and smell function, and, in some pat ients, examination of circumvallate taste buds by electron microscopy. Resu lts: Treatment success was predicated upon significant increases in parotid saliva gustin/CAVI. This occurred in 10 of the 14 patients who were labele d responders; they also exhibited improvement in taste and smell acuity, a diminution in dysgeusia and dysosmia and increased zinc concentrations in p arotid saliva, serum, and urine. Taste bud morphology returned to normal in each responder in whom it was measured. No increase in gustin/CAVI occurre d in 4 patients who were labeled nonresponders; they exhibited no improveme nt in taste or smell acuity and no increases in parotid saliva zinc. Howeve r, serum and urine zinc increased to levels similar to those measured in th e 10 responders. Two of 4 nonresponders reported diminution in dysgeusia an d dysosmia. Taste bud morphology did not change from the abnormal state in the 1 nonresponder in whom it was measured. Conclusions: Zinc treatment is effective in patients in whom this trace metal increases synthesis/secretio n of gustin/CAVI and ineffective in those in whom it does not. Increased gu stin/CAVI in this disorder is probably associated with zinc stimulation of the gene responsible for the synthesis/secretion of gustin/CAVI. Among nonr esponders, zinc was ineffective for several possible reasons, including res istance to zinc and possible sialylation of gustin/CAVI, which may render i t functionally ineffective. Results suggest the hypothesis that gustin/CAVI is a trophic factor that promotes growth and development of taste buds thr ough its action on taste bud stem cells.