Acrodermatitis Enteropathica

Updated: Jun 04, 2021
  • Author: Kristina Marie Dela Rosa, MD; Chief Editor: William D James, MD  more...
  • Print


Acrodermatitis enteropathica is a rare inherited form of zinc deficiency that was initially described by Brandt in 1936 and subsequently identified a as a definite disease by Danbolt and Closs in 1942. It is characterized by periorificial and acral dermatitis, alopecia, and diarrhea, and treatment requires lifelong zinc supplementation.



Zinc is an essential trace nutrient required for the proper function of more than 100 enzymes and plays a crucial role in nucleic acid metabolism. [1, 2]

Acrodermatitis enteropathica is an autosomal recessive disorder occurring as a result of mutations in the SLC39A4 (solute carrier family 39 member A4) gene located on band 8q24.3. [3, 4, 5] The SLC39A4 gene encodes a transmembrane protein that is part of the zinc/iron-regulated transporter–like protein (ZIP) family required for zinc uptake. [6, 7] This protein is highly expressed in the enterocytes in the duodenum and jejunum [8, 9] ; therefore, affected individuals have a decreased ability to absorb zinc from dietary sources. Absence of a binding ligand needed to transport zinc may further contribute to zinc malabsorption. [10]

Differentiating acquired zinc deficiency disorders from acrodermatitis enteropathica is difficult because they have similar clinical presentations. Acquired zinc deficiency can occur as a result of low nutritional intake, malabsorption, excessive loss of zinc, or a combination of these factors. [11, 12, 13] Acrodermatitis enteropathica can only be accurately diagnosed after attempts to remove zinc supplementation have failed. [14] Importantly, transient acquired zinc deficiencies can occur in premature infants secondary to their greater physiological demand for zinc and lower body stores. [15, 16] Additionally, zinc deficiency can present in full-term breastfed infants as a result of low maternal serum zinc levels or a defect in mammary zinc secretion. [1, 17] Thus, not all infants who have an acrodermatitis enteropathica–like presentation have the genetic disorder. In 2018, a case was also reported of acrodermatitis enteropathica due to total parenteral nutrition devoid of zinc as there was a recent shortage; the condition resolved upon addition of zinc into the total parenteral nutrition. [18]


Etiology of Acrodermatitis Enteropathica

The etiopathogenesis of the zinc deficiency occurs as a result of loss-of-function mutations of the zinc-ligand binding protein ZIP4 encoded by the SLC39A4 (solute carrier 39A) gene located on band 8q24.3. ZIP4 is a member of the Zrt-/Irt-like protein (ZIP) family, and it is a histidine-rich transmembrane protein that is specifically expressed on the apical side of enterocytes in the small intestine, as well as in the kidney, and is responsible for zinc absorption. [19]

Therefore, infants with an autosomal recessive mutation of this gene inadequately absorb dietary zinc. [20] A case has been reported of a patient with a mutation of SLC39A4 who had normal zinc levels and a mild phenotype. [21] Infants can also develop acrodermatitis enteropathica if their mothers have a mutation of the SLC30A2 gene located on band 1p36.11, which results in inadequate secretion of zinc into their breast milk. [22, 23]




The exact incidence of acrodermatitis enteropathica is unknown; however, it is estimated to occur 1 in 500,000 live births, with approximately 1.5 million people in the world affected. [24, 25, 26]


Acrodermatitis enteropathica has no racial predilection.


Acrodermatitis enteropathica has no sexual predilection.


Acrodermatitis enteropathica typically appears in the first few weeks after birth if the child is fed bovine milk or shortly after cessation of breastfeeding. [9] Acrodermatitis enteropathica can occur in children who are still breastfeeding if the levels of zinc are low in the breast milk. [22, 27]



With zinc supplementation, the response rate is 100%; however, without appropriate zinc supplementation, acrodermatitis enteropathica usually is lethal within the first few years of life. Untreated infants exhibit severe growth retardation, dermatitis, alopecia, secondary bacterial and fungal infections, and neurologic and behavioral changes; however, all symptoms are reversible with therapy.


Patient Education

Genetic counseling is recommended for family members of parents with the congenital form of acrodermatitis enteropathica.