Acrodermatitis enteropathica (AE) is a disorder of zinc metabolism caused by a defect in the absorption of zinc, that occurs in one of three forms: an inborn (congenital) form and two acquired forms. The inborn form of AE is a rare genetic disorder characterized by intestinal abnormalities that lead to the inability to absorb zinc from the intestine. The lack of zinc presents, characteristically, as: (1) skin inflammation with pimples (pustular dermatitis) occurring around the mouth and/or anus, (2) diarrhea, and (3) abnormal nails (nail dystrophy). In the acute phase, irritability and emotional disturbances are evident due to wasting (atrophy) of the brain cortex. It is important to recognize and treat this disorder. AE results from mutations in the zinc transporter gene SLC39A4 (solute carrier family 39 member A4), leading to improper enteral zinc absorption.
Acrodermatitis enteropathica is a rare skin disorder associated with zinc deficiency that is most often seen in infants. Zinc is a very important micronutrient that is essential for the proper functioning of the various metabolic and biochemical pathways of the body. The acquired form of this disorder generates similar symptoms. One transient form can result from the failure of the mother to secrete zinc into her breast milk. Other acquired forms of AE sometimes result after surgery to bypass some of the upper intestines or from special intravenous nutritional programs that are prepared without the appropriate amount of zinc. Supplemental zinc usually eliminates the symptoms.
Causes
The congenital form of acrodermatitis enteropathica is transmitted as an autosomal recessive genetic disorder. It appears to be the result of mutations in the SLC39A4 gene.
Genetic diseases are determined by a combination of genes for a particular trait that is on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier of the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Some women fail to generate adequate zinc levels in their breast milk – and that can also have a genetic cause. A single mutation in the SLC30A2 mutation can reduce breast milk zinc. This tendency does not require two gene abnormalities, one is sufficient and people who have this condition have a 50% chance of passing it on to their offspring.
Treatment
Acrodermatitis enteropathica is treated with zinc supplements in the form of zinc sulfate. These supplements should be given as soon as the diagnosis of the disorder is made and they have to be continued for life. The drug Diodoquin (iodoquinol) is another treatment that usually clears up symptoms within a week. If the disorder is caused by intravenous feeding, adding zinc supplements to the nutritional regimen can prevent and/or clear up manifestations of AE.
The management of the disease usually involves enteral or parenteral supplementation of zinc. Lifelong supplementation with 3 mg/kg/day of elemental zinc may be required. Several formulations are available, and zinc sulfate is the preferred oral formulation. Four milligrams of zinc sulfate contain about 1 mg of elemental zinc. Zinc chloride is preferred for parenteral supplementation. The clinical response is often dramatic and occurs shortly after initiating treatment, usually within a few days. The first sign of response to treatment is less irritability. Shortly after that, improvement in skin lesions is noted. While in therapy, regular monitoring of certain parameters is also required. This includes periodic measurement of zinc levels, complete blood counts, erythrocyte indices, serum copper level, and occult blood in the stool. Alkaline phosphate levels also may rise during treatment with zinc supplementation. High zinc levels in plasma may inhibit copper absorption due to competitive inhibition of a common cationic transporter; therefore, hypocupremia may result during therapy and should be monitored. Other adverse effects of zinc supplementation therapy could be gastric irritation and gastric hemorrhage.[7][8][9]
In cases of acquired zinc deficiency, the doses required for zinc supplementation are variable, depending on the underlying cause. Patients with malabsorption may need higher doses for response to treatment. Compresses and emollients applied to the affected areas may help in re-epithelialization when used along with zinc supplementation.
Genetic counseling is recommended for families of patients with the congenital form of acrodermatitis enteropathica.
References
Acrocallosal Syndrome
