Transient neonatal zinc deficiency occurs in breast-fed infants as a consequence of low milk zinc concentration in their nursing mothers, which cannot be corrected by maternal zinc supplementation. A large amount of zinc, an essential trace mineral, is ... Transient neonatal zinc deficiency occurs in breast-fed infants as a consequence of low milk zinc concentration in their nursing mothers, which cannot be corrected by maternal zinc supplementation. A large amount of zinc, an essential trace mineral, is required for normal growth particularly in infants, and breast milk normally contains adequate zinc to meet the requirement for infants up to 4 to 6 months of age. Zinc deficiency can lead to dermatitis, alopecia, decreased growth, and impaired immune function. The disorder shows autosomal dominant inheritance with incomplete penetrance (summary by Chowanadisai et al., 2006). Some aspects of TNZD resemble the more severe disorder acrodermatitis enteropathica (AEZ; 201100), an autosomal recessive disorder caused by mutation in the zinc transporter SLC39A4 (607059). However, infants with transient neonatal zinc deficiency do not require zinc supplementation following weaning and have normal zinc absorption, whereas those with AEZ require lifelong zinc supplementation (summary by Chowanadisai et al., 2006).
Sharma et al. (1988) showed that the condition in humans predisposing mothers to produce zinc-deficient breast milk is inherited. They described an Indian pedigree in which 10 children in 3 interrelated families were affected with a variant of ... Sharma et al. (1988) showed that the condition in humans predisposing mothers to produce zinc-deficient breast milk is inherited. They described an Indian pedigree in which 10 children in 3 interrelated families were affected with a variant of acrodermatitis enteropathica (201100) that had its onset before weaning and disappeared when the child started a normal solid diet. The pedigree pattern and consanguinity suggested autosomal recessive inheritance. Sharma et al. (1988) suggested the designation 'self-limiting acrodermatitis enteropathica.' Glover and Atherton (1988) described transient zinc deficiency in 2 full-term breast-fed sibs that could be related to low maternal breast milk zinc concentration. Chowanadisai et al. (2006) reported a large family in which 2 women had infants affected with transient neonatal zinc deficiency. Both infants were exclusively breast-fed for 5 months and developed severe zinc deficiency manifest as severe dermatitis and alopecia. The mothers had low zinc concentration in breast milk, but normal zinc levels in serum. Dermatitis improved significantly in both infants after 1 week of zinc supplementation and did not recur with cessation of zinc treatment after weaning. Lasry et al. (2012) reported 2 unrelated women of Ashkenazi Jewish descent, each of whom had an infant with transient neonatal zinc deficiency. The 2 infants were exclusively breast-fed, and both showed severe dermatitis particularly affecting the face and perineal regions. One developed partial alopecia of the eyebrows, eyelashes, and temple area. Both responded rapidly and well to oral zinc supplementation. Analysis of the mothers' breast milk showed low zinc content. Family history of 1 infant revealed that her brother had been exclusively breast-fed and had mild dermatitis that responded to zinc supplementation. The second infant had 2 sisters that were exclusively breast-fed but showed no symptoms of zinc deficiency.
In 2 female relatives, each of whom had an infant with transient neonatal zinc deficiency, Chowanadisai et al. (2006) identified a heterozygous mutation in the SLC30A2 gene (H54R; 609617.0001). In vitro cellular expression studies indicated that the mutant ... In 2 female relatives, each of whom had an infant with transient neonatal zinc deficiency, Chowanadisai et al. (2006) identified a heterozygous mutation in the SLC30A2 gene (H54R; 609617.0001). In vitro cellular expression studies indicated that the mutant protein formed insoluble perinuclear intracellular aggregates, resulting in decreased abundance of functional SLC30A2 and decreased zinc excretion by the maternal mammary epithelial cells into breast milk. Lasry et al. (2012) identified a heterozygous mutation in the SLC30A2 gene (G87R; 609617.0002) in 2 unrelated women of Ashkenazi Jewish descent, each of whom had an infant with transient neonatal zinc deficiency. In vitro functional expression studies in various cell lines showed that the mutant protein caused impaired zinc secretion and mislocalization of the protein. Coexpression of the mutant protein and the wildtype protein indicated a dominant-negative effect for the G87R mutation. - Exclusion Studies The mouse lm phenotype is caused by mutation in the Znt4 gene (602095). To investigate whether changes in the ZNT4 gene are responsible for reduced zinc in breast milk in humans, Michalczyk et al. (2003) studied 2 unrelated mothers with low zinc milk levels whose babies had developed zinc deficiency. Their findings suggested that the lm mouse is not the corresponding model for the human zinc deficiency condition.