Acrodermatitis enteropathica, zinc-deficiency type (AEZ), is a rare autosomal recessive disease caused by severe zinc deficiency. It typically appears in the first few weeks after birth if the child is fed bovine milk or shortly after cessation of breastfeeding. AEZ is characterized by acral dermatitis, alopecia, diarrhea and growth failure. Other features associated with severe and chronic zinc deficiency include failure to thrive, mental slowness, photophobia, hypogeusia, anemia, poor wound healing, hypogonadism in males, and delayed puberty.
Diagnosis of AEZ is based on the symptoms (diarrhea and acral dermatitis) and laboratory testing for plasma zinc concentrations and serum alkaline phosphatase. Affected patients have low levels of zinc and alkaline phosphatase. Also, molecular genetic testing for the SLC39A4 gene mutations could be performed to confirm the diagnosis.There is no cure for the AEZ disease. However, zinc supplementation therapy for lifetime results in the disappearance of the symptoms. Without appropriate zinc supplementation, acrodermatitis enteropathica usually is lethal within the first few years of life.
Mutations in the SLC39A4 gene are the cause of acrodermatitis enteropathica, zinc-deficiency type (AEZ). SLC39A4 gene encodes a zinc transporter protein called the Zip4 transporter, which plays an important role in the transcellular absorption of zinc into the enterocytes of the duodenum and jejunum. Defects in this protein lead to zinc malabsorption, causing the symptoms of AEZ disease.
[See: Jordan > Wang et al., 2001].
To map the gene responsible for AEZ, Wang et al. (2001) performed a genome-wide screen of 17 individuals, including four affected individuals, in a consanguineous Jordanian family. All four affected individuals, as well as an affected member not genotyped in the genome-wide screen, were found to be homozygous for a common haplotype, spanning approximately 3.5 cM, defined by markers D8S1713 and D8S2334 on chromosome 8q24.3. To support these mapping data, seven consanguineous Egyptian families with eight patients with AEZ were genotyped using these markers, and six patients from five families were found to be homozygous in this region. Multipoint analysis with all consanguineous families resulted in a maximum lod score of 3.89 between D8S1713 and D8S373.
Ohlsson (1981) described a Saudi boy who, despite being breast fed, developed acrodermatitis enteropathica. The mother had zinc deficiency as indicated by low serum levels of zinc. Cranial computed tomography showed marked cortical atrophy that improved on treatment with zinc.
Mostafa and Al-Zayer (1990) described four patients (three girls and one boy) with acrodermatitis enteropathica form Saudi Arabia. All patients were born to consanguineous parents, two were sisters (1 and 2) and the other two patients (3 and 4) had a sibling who died from the same disease. Candida infection was found in all cases. Patients 1, 3 and 4 had Staphylococcus infection, patient 2 had Klebsiella oxytoca, Streptococcus pyogenes and Escherichia coli infections, and patient 1 had Pseudomonas pyocyaneus infection. Patient 4 also had hyperkeratosis, parakeratosis, and acanthosis in the epidermis with few dyskeratotic cells. All patients presented with iron deficiency anemia. Zinc sulfate therapy was given to all affected patients.