Zinc acrodermatitis enteropathica

Although genetic defects in the metahoUsm of trace elements are rare, they are nonetheless important because of the information they have provided as to homeostatic control mechanisms. This in turn has led to development of effective therapeutic strategies. The most commonly investigated disorders are those affecting iron (hemochromatosis), copper (Wilson s disease and Menkes syndrome), zinc (acrodermatitis enteropathica), and molybdenum (molybdenum cofactor disease). 

Evidence for a similar membrane carrier for zinc in humans has been suggested from studies of zinc uptake in acrodermatitis enteropathica. In 1979, using mucosal samples obtained from acrodermatitis patients, Atherton e reported that, at lower lumenal zinc concentrations, brush border zinc uptake was inhibited in these patients, an effect overcome at higher zinc concentrations (48). As a result of these studies, they suggested the possibility of a membrane associated carrier for zinc in the brush border membrane. In the acrodermatitis enteropathica patients, this carrier could be altered or absent. Their hypothesis is supported by findings in rats by both Davies (38) and by this laboratory (43). 

The symptoms of the disease can be ameliorated by dietary zinc supplementation. The differential diagnosis of the disease includes acquired zinc deficiency condition owing to low-zinc level in mother s milk because both conditions are very similar in terms of onset and clinical features. As soon as the low-zinc breastfed infants are weaned, they no longer require supplemental zinc, but acrodermatitis enteropathica patients experience recurrence of symptoms if they discontinue oral zinc therapy. 

A variety of symptoms, not mentioned earlier, have also been associated with zinc deficiency. Zinc deficiency is thought to delay woxmd healing, impair the senses of taste and smell, and impair the functions of the immune system. (The impaired sense of taste is called hypogettsia.) Severe zinc deficiency results in impairment of the immune system and increased infections. These problems have been found in the severe deficiencies that occur in starvation (marasmus) and acrodermatitis enteropathica and in studies with animals. The immune system involves a large array of hormones, hormone receptor proteins, signaling proteins, and DNA-binding proteins, some of which require zinc for activity. It is not clear which of these components is most sensitive to zinc deficiency. 

Clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) was used 30 years ago as an oral antiparasitic agent and to increase the intestinal absorption of zinc in patients with acrodermatitis enteropathica, a genetic disorder of zinc... 

Zinc deficiency occurs in a rare genetic disease, acrodermatitis enteropathica. The disease develops in the early months of life, produces pigmented areas on the elbows, knees, face, and buttocks, and is fatal if left untreated. The disease results from an impairment in zinc absorption. Intestinal disturbances, diarrhea, and growth failure also occur. The disease can be treated successfully by administering oral zinc at two times the RDA (Grider and Yoimg, 1996). 

Grider, A., and Young, E. M. (1996). The acrodermatitis enteropathica mutation transiently affects zinc metabolism in human fibroblasts. /. Nutr. 126,219-224. 

Failure to include zinc in fluids for total parenteral nutrition (TPN) is another example of iatrogenically induced, conditioned deficiency of zinc. A decline of plasma zinc has been observed in several patients given TPN fluids containing less than 1.25 mg of zinc daily (9,58). The decrease which occurred was probably not attributable to urinary losses. Some patients on TPN have developed a clinical picture resembling acrodermatitis enteropathica. 

Zinc deficiency occurring in patients following penicillamine therapy for Wilsons disease has been reported recently (59). The manifestations consisted of parakeratosis, "dead hair and alopecia, keratitis, and centro-cecal scotoma. The clinical features were similar to those of acrodermatitis enteropathica. Following supplementation with zinc, several clinical manifestations were reversed. 

Following treatment of acrodermatitis enteropathica with diiodohydroxyquinolone (X) the absorption and retention of dietary zinc and other trace metals has been found to be greater than in subjects not receiving the... 

Acrodermatitis Enteropathica. Acrodermatitis entero-pathica (AE) is characterized by periorificial and acral dermatitis, alopecia, and diarrhea. Patients with this disorder have abnormally low blood zinc levels (<30 Llg/dL) symptoms are reversed by oral zinc supplementation, with this being diagnostic.This formerly fatal condition is an autosomal recessive inborn error affecting zinc absorption from the intestinal mucosa, but the location of the gene defect has not yet been identified. 

Barnes PM, Moynahan EJ. Zinc deficiency in acrodermatitis enteropathica multiple dietary intolerance treated with synthetic diet. Proc R Soc Med 1973 66 327-9. 

The ZIP family are involved in Zn transport into the cytosol, mostly across the plasma membrane. Although the human genome encodes 14 ZIP-related proteins, Z1P4 appears to mediate Zn uptake. It s involvement in dietary Zn uptake into intestinal enterocytes is well estabhshed, and mutations in Z1P4 have been found in patients with acrodermatitis enteropathica, a recessive disorder of Zn absorption which results in Zn deficiency. DMTl is probably also involved in the transport of dietary zinc across the brush border membrane of the intestine. 

Plate 2 An inability to acquire sufficient bioavailable zinc from the gastrointestinal tract produces acrodermatitis enteropathica which readily yields to the administration of zinc complexes. Photograph reproduced with permission from National Medical Slide Bank... 

Acrodermatitis enteropathica (AE) is an autosomal recessive disorder characterized by defective absorption of zinc, thickened, ulcerated skin on the extremities and around body orifices, alopecia, diarrhea, growth failure, and abnormalities in immune function. The concentration... 

When oral zinc supplementation is used therapeutically in patients with rheumatoid arthritis, there is a rise in serum alkaline phosphatase values which correlates highly with the increase in serum zinc (S42). This positive correlation between serum zinc and serum alkaline phosphatase levels has also been demonstrated in patients with congenital acrodermatitis enteropathica (W15) and it has been suggested that serum alkaline phosphatase measurements may be employed as a useful index of serum zinc levels in these patients (W15). 

W15. Weisman, K., and Hdyer, H., Serum alkaline phosphatase activity in acrodermatitis enteropathica An index of the serum zinc level. Acta Derm. Venereal. 59, 89-90 (1979). 

Zinc (200 to 220 mg p.o. t.i.d.) is used in zinc-deficiency states and as an adjunct in ulcers, acne, ear granulomata, rheumatoid arthritis, hypogeusia, anosmia, vitamin A therapy, and acrodermatitis enteropathica. In addition, zinc has antiinfective properties and hence is used twice a day as an ophthalmic solution (1 to 2 drops). Zinc sulfate ophthalmic solution exhibits astringent and weak antiseptic activity, which may result from precipitation of protein by the zinc ion and by clearing mucus from the outer surface of the eye. This drug has no decongestant action and produces mild vasodilation. 

Acrodermatitis enteropathica is an autosomal recessive genetic zinc deficiency which causes parakeratosis of the skin and lowered zinc levels in the plasma (Moynahan 1974). 

Certain inherited diseases are associated with abnormal trace metal metabolism, and this may be linked to MT synthesis, either directly or indirectly. Zinc, copper, and iron are the target elements in several diseases, and their concentrations may be altered in disorders of the central nervous system or other physiological systems, including Alzheimer-type dementia, amyotrophic lateral sclerosis, acrodermatitis enteropathica, biliary cirrhosis, Wilson s and Menke s diseases (Bremner 1987), epi-... 

Zinc Deficiency in Humans Much of the knoivledge relating to severe zinc deficiency in humans has been derived from studies of individuals born with acrodermatitis enteropathica, a genetic disorder resulting from the impaired uptake and transport of zinc. The signs and symptoms of zinc deficiency are outlined in Table 29.3. 

Different zinc preparations are available for treatment of acute and severe deficiencies. In general, most cases of hypozincemia rapidly respond to zinc therapy. In acrodermatitis enteropathica, zinc therapy results in a prompt clinical and biochemical remission. Without treatment, there was frequently a fatal outcome during early childhood. Zinc supplementation also increased the height-for-age scores in children (Wal-ravens et al. 1983). 

Lombeck I, Schnippering HG, Ritzl E, Eeinen-DEGEN LE and Bremer Hf (1975) Letter Absorption of zinc in acrodermatitis enteropathica. Lancet 1 855. 

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