Zinc deficiency and its inherited disorders -a review

Abstract

Zinc is an essential trace element required by all living organisms because of its critical roles both as a structural component of proteins and as a cofactor in enzyme catalysis. The importance of zinc in human metabolism is illustrated by the effects of zinc deficiency, which include a diminished immune response, reduced healing and neurological disorders. Furthermore, nutritional zinc deficiency can be fatal in newborn or growing animals. While zinc deficiency is commonly caused by dietary factors, several inherited defects of zinc deficiency have been identified. Acrodermatitis enteropathica is the most commonly described inherited condition found in humans. In several of the few cases that have been reported, this disorder is associated with mutations in the hZIP4 gene, a member of the SLC39 family, whose members encode membranebound putative zinc transporters. Mutations in other members of this family or in different genes may account for other cases of acrodermatitis in which defects in hZIP4 have not been detected. Another inherited form of zinc deficiency occurs in the lethal milk mouse, where a mutation in ZnT4 gene, a member of the SLC30 family of transmembrane proteins results in impaired secretion of zinc into milk from the mammary gland. A similar disorder to the lethal milk mouse occurs in humans. In the few cases studied, no changes in ZnT4 orthologue, hZnT4, were detected. This, and the presence of several minor phenotypic differences between the zinc deficiency in humans and mice, suggests that the human condition is caused by defects in genes that are yet to be identified. Taking into account the fact that there are no definitive tests for zinc deficiency and that this disorder can go undiagnosed, plus the recent identification of multiple members of the SCL30 and SLC39, it is likely that mutations in other genes may underlie additional inherited disorders of zinc deficiency.

Supplementation of zinc mitigates the altered uptake and turnover of 65Zn in liver and whole body of diabetic rats

“…The biological requirement of Zn implies the existence of homeostatic mechanism that regulates its absorption, cellular uptake, distribution among intracellular compartments and macromolecules, as well as excretion. Such a mechanism is needed to maintain the broad range of biochemical functions that are dependent on Zn proteins and enzymes (Ackland and Michalczyk 2006). There are many reports that indicate the role of zinc transporters in influx and efflux of the zinc and intracellular compartmentalization of zinc in various tissues (Eide 2000;Kambe T et al 2002;Liuzzi and Cousins 2004;Iram et al 2005).…”

Study of Serum Copper and Iron in Children with Chronic Liver Diseases

“…The disorder manifests itself in premature breast fed infants, who demonstrate symptoms characteristic to nutritional Zn deficiency including dermatitis, diarrhea, alopecia, loss of appetite, impaired immune function and neuropsychiatric changes. This condition has been reported in preterm babies (27 to 33 weeks gestation); and less commonly in term babies [86,100].…”

Overview of Inherited Zinc Deficiency in Infants and Children

“…Breast milk zinc concentrations, particularly in the first 3 mo, are considerably higher than those of the maternal serum, which reflects the infant's requirement of a large amount of zinc for growth and development. Compared with full-term infants, preterm infants are in negative zinc balance at birth because of the lower capacity for gut absorption (6), and thus the demand for zinc increases rapidly in thriving preterm infants (7). Hence, the preterm infant has an increased risk of zinc deficiency and symptomatic zinc deficiency has been mostly found in breast-fed preterm infants (8).…”