Acrodermatitis enteropathica

Aggett, Peter

doi:10.1007/bf01811322

Cited by 51 publications

(29 citation statements)

References 61 publications

(47 reference statements)

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“…Patients suffering from AE display classic symptoms of zinc deficiency including dermatitis, diarrhea, growth retardation, immune dysfunctions, and occasionally, neuropsychological disturbances, which could be ameliorated by oral zinc supplementation (17,18). Human ZIP4 has been identified as the gene responsible for AE (19,20).…”

Section: Zinc Uptake Across the Apical Membrane Into Enterocytesmentioning

confidence: 99%

Dietary zinc absorption: A play of Zips and ZnTs in the gut

2010

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SummaryStudies on dietary zinc absorption are of fundamental nutritional significance, owing to the ubiquity of zinc in biological processes and the severe outcomes of zinc deficiency in humans. Insights into the molecular basis of dietary zinc absorption have advanced in recent years through functional characterization of zinc transporters in cell culture, immunohistochemical studies on rodent intestine and analysis of gene knockout mice. Zinc transporters with manifested expression in enterocytes include ZnT1, ZnT2, ZnT4, ZnT5, ZnT6, ZnT7, Zip4, and Zip5. Among them, ZIP4, the gene responsible for Acrodermatitis enteropathica, an inherited human zinc deficiency, mediates dietary zinc uptake into enterocytes across the apical membrane, while ZnT1 is involved in zinc efflux from enterocytes across the basolateral membrane into circulation. The intracellular trafficking pathways for zinc retention and movement between apical and basolateral sides of the enterocytes have yet to be defined. The utilization of Drosophila model in elucidating molecular mechanisms of dietary zinc absorption is also discussed in this review.

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Section: Zinc Uptake Across the Apical Membrane Into Enterocytesmentioning

confidence: 99%

Dietary zinc absorption: A play of Zips and ZnTs in the gut

2010

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“…Zinc deficiency in the breast fed babies is caused by the low levels of zinc in the maternal milk. In acrodermatitis enteropathica, however, the maternal milk is protective and the symptoms of zinc deficiency develop after weaning (Aggett 1983). No impairment in zinc uptake in the gut was found in the breast-fed zinc-deficient babies (Aggett et al 1980).…”

Section: Introductionmentioning

confidence: 98%

Analysis of zinc transporter, hZnT4 ( Slc30A4 ), gene expression in a mammary gland disorder leading to reduced zinc secretion into milk

et al. 2003

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Zinc deficiency, causing impaired growth and development, may have a nutritional or genetic basis. We investigated two cases of inherited zinc deficiency found in breast-fed neonates, caused by low levels of zinc in the maternal milk. This condition is different from acrodermatitis enteropathica but has similarities to the "lethal milk" mouse, where low levels of zinc in the milk of lactating dams leads to zinc deficiency in pups. The mouse disorder has been attributed to a defect in the ZnT4 gene. Little is known about the expression of the human orthologue, hZnT4 (Slc30A4). Sequence analysis of cDNA, real-time PCR and Western blot analysis of hZnT4, carried out on control cells and cells from unrelated mothers of two infants with zinc deficiency, showed no differences. The hZnT4 gene was highly expressed in mouthwash buccal cells compared with lymphoblasts and fibroblasts. The hZnT4 protein did not co-localise with intracellular free zinc pools, suggesting that hZnT4 is not involved in transport of zinc into vesicles destined for secretion into milk. This observation, combined with phenotypic differences between the "lethal milk" mouse and the human disorder, suggests that the "lethal milk" mouse is not the corresponding model for the human zinc deficiency condition.

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“…Mutations in this gene have recently been shown to be the cause of the autosomal recessive disease of zinc uptake, acrodermatitis enteropathica (36,37). Although some of the mutations described in this gene would be expected to have very significant effects on protein confirmation and function (38), acrodermatitis enteropathica responds clinically to high-dose zinc supplementation (39). This suggests that other, lower-affinity, or less-specific, transport proteins are involved in gastrointestinal absorption of zinc.…”

Section: Discussionmentioning

confidence: 99%

Zinc Metabolism in Adolescents with Crohn's Disease

et al. 2004

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Low serum zinc concentrations have been reported in Crohn's disease (CD) and overt zinc deficiency has been described, but little is known about the effect of CD on zinc metabolism in adolescents. The aim of this study was to measure zinc absorption, endogenous fecal zinc excretion, urinary zinc excretion, and zinc balance in children with stable CD and in matched controls. Subjects were 15 children, ages 8 -18 y, with stable CD, and 15 healthy matched controls. Subjects were adapted to diets providing 12 mg/d elemental zinc for 2 wk, and then admitted for a 6-d metabolic study. Stable zinc isotopes were given intravenously and orally, and urine and feces collected for 6 d. Fractional zinc absorption, endogenous fecal zinc excretion, and zinc balance were calculated using established stable isotope methods. In subjects with CD, zinc absorption (10.9% Ϯ 6.1 versus 23.4 Ϯ 15.8, p ϭ 0.008) and plasma zinc concentration (0.85 mg/dL Ϯ 0.15 versus 1.25 Ϯ 0.35, p ϭ 0.004) were significantly reduced, compared with controls. Despite this, there were no significant differences in endogenous fecal zinc excretion (2.0 mg Ϯ 1.5 versus 1.5 Ϯ 1.5, p ϭ 0.34) or urinary zinc excretion (0.9 mg Ϯ 0.7 versus 1.0 Ϯ 0.7, p ϭ 0.47). Zinc balance was significantly lower in CD (Ϫ1.5 mg Ϯ 1.5) than in controls (ϩ0.6 mg Ϯ 3.1, p Ͻ 0.0001). In conclusion, adolescents with CD have significantly reduced zinc absorption. Despite this, they were unable to reduce endogenous fecal zinc excretion to restore normal zinc balance and had a significantly worse zinc balance and lower plasma zinc concentration than controls. Crohn's disease (CD) is a chronic, progressive inflammatory disorder that can affect the entire length of the gastrointestinal tract. Children with CD often present with growth stunting, weight loss, and nutritional deficiencies due to anorexia, poor intestinal absorption, and increased losses of nutrients in the gastrointestinal tract (1).Zinc is a component of over 200 enzymes and is essential for normal immune function, DNA and RNA synthesis, and gene transcription. Zinc is absorbed along the length of the small intestine and is transported to the liver in the portal circulation. It is excreted into the gut (endogenous fecal zinc excretion), and pancreatic and biliary secretions contain large amounts of zinc, most of which is subsequently reabsorbed. Zinc homeostasis is maintained by changes in fractional zinc absorption and in endogenous fecal zinc excretion (2). Endogenous fecal zinc excretion increases during periods of high zinc intake (3) and decreases during periods of zinc restriction (4).Severe zinc deficiency leads to clinical features of acrodermatitis such as alopecia, anorexia, diarrhea, dermatitis, poor growth, and impaired immune function, and children are at especially high risk for zinc deficiency due to their high requirements for normal growth (2). Zinc deficiency was first reported in CD in the 1970s (5-7), and, in extreme cases, the clinical features of acrodermatitis have been described (8 -11). The incidenc...

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Acrodermatitis enteropathica

Cited by 51 publications

References 61 publications

Dietary zinc absorption: A play of Zips and ZnTs in the gut

Dietary zinc absorption: A play of Zips and ZnTs in the gut

Analysis of zinc transporter, hZnT4 ( Slc30A4 ), gene expression in a mammary gland disorder leading to reduced zinc secretion into milk

Zinc Metabolism in Adolescents with Crohn's Disease

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