Excerpt from Acrodermatitis Enteropathica

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Background

Acrodermatitis enteropathica (AE) is an inborn error of zinc metabolism that is inherited as an autosomal recessive disorder. Symptoms in infancy typically include periorificial and acral dermatitis, diarrhea, behavioral changes, and neurologic disturbances. In older children, failure to thrive, anorexia, alopecia, nail dystrophy, and repeated infections are most common.

Zinc deficiency may be due to inadequate intake, malabsorption, excessive loss, or a combination of these factors. If treated early, most of the symptoms are reversible and usually cause no sequelae.

Pathophysiology

The pathophysiology of AE remains unclear and continues to be debated. Zinc is an essential trace element for life It is not only an important nutrient and cofactor of enzymes and transcription factors but also an intracellular mediator, similar to calcium.

Zinc homeostasis results from a coordinated regulation by different proteins involved in uptake excretion and intracellular storage of zinc. Intracellular molecular pathways were recently discovered to be involved in zinc homeostasis.

In 2001, Wang et al mapped the AE genetic locus to band 8q24.3. More recently, a group of proteins, the SLC39 proteins that are members of the broad ZIP family of metal ion transporters, were implicated in playing a role in zinc uptake across the plasma membrane of various cell types. These proteins transport metal ions from the cell exterior or lumen of intracellular organelles into the cytoplasm. Their principal function is to provide zinc to new synthesized proteins, a process important for several functions, such as gene expression, immunity, reproduction or protection against free-radical damage. The human genome encodes for 14 SLC39-related proteins. SLC39A4 is specifically implicated in the uptake of dietary zinc into intestinal enterocytes. Mutations in its gene have been identified in patients with AE.

In infants with AE, an absence of a binding ligand may contribute to zinc malabsorption during weaning. Such a ligand has been identified in normal pancreatic secretions as well as in human milk. Other causes, such as high phytate concentrations found in cereals and soy milk, inhibit zinc absorption. Geophagia, which Prasad (1995) described, decreases zinc absorption.

AE was recently reported as a presentation of food allergy. Serum total immunoglobulin E (IgE) and food-specific IgE levels to milk, soybean, wheat, and peanut have been measured to evaluate for food allergy. Undiagnosed food allergy can lead to profound zinc deficiency. Food allergy should be suspected in children with acquired AE.

Mortality/Morbidity

Untreated patients usually die in the first few years of life. They have severe growth retardation, dermatitis, alopecia, secondary bacterial and fungal infections, and neurologic and behavioral changes. All of these conditions are reversible with therapy. Therapy achieves a survival rate of 100%.

Race

No race predilection is reported.

Sex

No sex predilection is reported.

Age

Symptoms typically appear in the first few months of life, when an infant is weaned from breastfeeding. However, symptoms of AE can develop in full-term breastfed infants as a result of zinc deficiency in breast milk and decreased maternal plasma zinc levels.

AE-like symptoms have also been described in older children and adults who are receiving prolonged parenteral nutrition without zinc supplementation

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