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Acrodermatitis enteropathica
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Acrodermatitis enteropathica (AE) OMIM 201100 is a rare, autosomal-recessive, inherited disorder of zinc deficiency. It is caused by mutations in the SLC39A gene located on 8q24.3, which encodes for ZIP4 intestinal zinc transporter expressed in enterocytes that absorb dietary zinc from the small intestine. The estimated prevalence is 1 in 500,000 children worldwide, without apparent predilection for race or gender. AE manifests itself shortly after birth in a bottle-fed infant and sometime soon after weaning in a breast-fed infant. Zinc within breast milk is more bioavailable to infants than within bovine milk due to binding to a low-molecular-weight ligand secreted by the pancreas. Characteristic clinical signs are lesions in acral and periorificial sites; the first signs are eczematous, pink, scaly plaques that can become vesicular, bullous, pustular, or desquamative. They can resemble the severe diaper dermatitis of infancy or biotin deficiency. Angular cheilitis and paronychia can also be seen early. If left untreated, AE usually causes diarrhea, irritability, and alopecia, and skin lesions become secondarily infected with bacteria and Candida albicans. Impaired physical and mental development is seen in advanced disease. Appropriate supplementation of zinc in the infant’s diet results in a rapid improvement.
The diagnosis of AE is applied only to inherited zinc deficiency; non-inherited zinc deficiency is called acquired zinc deficiency. Transient neonatal zinc deficiency OMIM 608118, caused by mutations of the ZnT2/SLC30A2 in mothers, occurs in breast-fed, full-term infants due to low zinc concentrations in the mother’s breast milk. Clinical symptoms identical to AE are alleviated with zinc supplementation to the infant, but not to the mother. Long-term therapy and management of zinc deficiency vary depending on the severity of the disorder.
Management Strategy
Chronic dermatitis in periorificial and acral areas should suggest the possibility of zinc deficiency but establishing the diagnosis of AE may be difficult. The first step is laboratory determination of blood plasma or serum zinc levels. A blood sample needs to be drawn into a trace element–free bottle with a stainless steel needle. Avoid contact with rubber stoppers as they contain zinc, avoid hemolysis, use zinc-free anticoagulants, and separate plasma or serum from cells within 45 minutes. Zinc levels will decrease in states of hypoalbuminemia because zinc binds albumin in the circulation. If the diagnosis of zinc deficiency has been confirmed, management becomes relatively simple: oral zinc supplementation produces dramatic resolution of the problem. High-dose supplementation will allow for increased paracellular zinc absorption despite the absence of a functional ZIP4 zinc transporter.
The patient or his or her family must understand the need for lifelong management of the disorder in terms of zinc supplementation and medical supervision. Discuss foods rich in zinc, such as shellfish, nuts, and green leafy vegetables . Bioavailability of zinc can be reduced by phytates, which naturally occur in plant fibers, and with regular iron supplementation. With age and a more varied diet, the dose of daily zinc supplementation may be reduced. Zinc therapy should be monitored periodically with a morning fasting specimen, full blood count, serum copper level, and stool examination for occult blood. Zinc supplementation has a theoretical risk of reducing copper absorption, leading to refractory microcytic anemia that will not respond to iron therapy until the serum copper level is normalized.
Specific Investigations
The normal plasma zinc level is 70–110 mcg/dL and in serum 80–120 mcg/dL. Urinary zinc can be measured but is not definitive for diagnosis.
Homozygosity mapping places the acrodermatitis enteropathica gene on chromosomal regions 8q24.3
Wang K, Pugh EW, Griffen S, et al. Am J Hum Genet 2001; 68: 1055–70.
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