The therapeutic effect of amphotericin in acrodermatitis enteropathica: Hypothesis and implications

Abstract

A nine year-old girl with acrodermatitis enteropathica developed typical clinical and biochemical features of zinc deficiency on two occasions while on an oral zinc supplement. On both occasions, these features responded immediately when she was treated with amphotericin B lozenges. Studies in vitro showed that amphotericin increases the permeability to zinc of pure lipid membranes containing cholesterol. We suggest that the antibiotic enhanced zinc absorption from the oral supplement thereby effecting resolution of the patient's zinc deficiency.

Impact of Zinc Transport Mechanisms on Embryonic and Brain Development

“…Infants suffering from TIZD display Zn deficiency due to low milk Zn concentration in their nursing mothers, which cannot be corrected by maternal Zn supplementation. The symptoms of TIZD cannot be distinguished from AE, the genetic form of Zn deficiency, except by the fact that Zn deficiency is detected after weaning in AE, since breast milk displays protective effects by bringing maternal source of Zn [53]. Mutations in ZIP4 mutations are known to cause AE, which is a rare autosomal recessively inherited disorder of intestinal Zn malabsorption that is also called "genetic Zn deficiency," [23,[54][55][56].…”

Zinc deficiency and its inherited disorders -a review

“…Acrodermatitis enteropathica was first identified as a zinc deficiency disease when it was discovered that the symptoms could be abolished by oral zinc supplementation (Moynahan, 1974). Prior this finding, the antibiotic amphotericin B, which increases membrane permeability to divalent cations, was used effectively in the treatment of symptoms, presumably because the defective zinc transport system was bypassed (Aggett et al, 1981). The defect in this disorder was shown to result in an impairment of zinc absorption in the gut, where patients with acrodermatitis enteropathica showed decreased intestinal absorption of 65 Zn (Weismann et al, 1979) and nett intestinal secretion of 65 Zn was reduced (Aggett et al, 1978).…”

“…Disturbances in lipid metabolism including reduced enteral absorption of unsaturated fatty acids also occur (Mack et al, 1989). The plasma zinc levels in untreated patients with acrodermatitis enteropathica, are generally reduced (ranging from 0.33mmol/L to 8.1μmol/L) (Chandra, 1980;Ozkan et al, 1999;Anttila et al 1984;Neldner and Hambidge, 1975;Weismann et al, 1983;Weismann et al, 1980;Aggett et al, 1981;Graves et al, 1980;Oleske et al, 1979;Walravens et al, 1978;Bohane et al, 1977;Kelly et al, 1976;Bronson et al, 1983), although normal (11.5-22.5μmol/L) (Mack et al, 1989, Chandra, 1980 and higher (23.2μg/g dry weight relative to normal 10.4-11.9μg/g dry weight) (Garretts and Molokhia, 1977) serum zinc levels have been reported. The variations in serum zinc in both nutritional and inherited forms of zinc deficiency suggest that serum zinc levels do not reflect overall body zinc status and that the symptoms of zinc deficiency may be due to a depletion of zinc from specific intracellular pools, for example membrane-bound zinc fractions (Jackson et al, 1984;Bettger and O'Dell, 1981).…”

Paediatric gastroenterology: lessons of inborn errors

“…Using a metabolic balance technique (Aggett et al, 1978) we have shown that AE patients receiving no Zn+ + supplements are in a net secretory state with respect to Zn+ + which reverts to net absorption when oral supplements are given. In vitro jejunal biopsy studies allowed us to demonstrate that steady state uptake of 65Zn in vitro is markedly reduced compared to controls and is equally apparent whether on or off zinc supplementation (Atherton et al, 1979).…”