Transient neonatal zinc deficiency (TNZD) is a genetic condition that presents with dermatitis, alopecia, diarrhea, and growth faltering in breast milk-fed infants of females with a heterozygous pathogenic variant in SLC30A2, the primary zinc transporter in mammary glands. Despite being an easily treatable condition, effectively evaluating for TNZD can be challenging because the infant's genotype does not reliably reflect the mother's genotype. Herein, we present our approach to diagnosis in an exclusively breastfed 5-month-old infant with treatment-refractory eczematous rash, admitted for growth faltering and decreased serum zinc and alkaline phosphatase levels. The infant was diagnosed with TNZD via trio genome-based exome sequencing after a heterozygous SLC30A2 variant of uncertain significance (VUS) (c.927G>C; p.Trp309Cys) was identified in the proband's mother, which was notably absent in the proband. Breast milk zinc concentration (Zn) was measured in duplicate via inductively coupled mass spectrometry in 10 samples (3 from the proband's mother and 7 from unrelated controls) and measured -265, -144, and -46 μg/dL below expected Zn at 0, 5, and 7 months postpartum, respectively, compared to an average deviation of -29 μg/dL in controls. Zinc supplementation in the infant led to rapid clinical improvement. The absence of the maternal SLC30A2 variant in the proband underscores diagnostic challenges in evaluating for TNZD, as primary variant analysis is typically limited to the proband in trio testing. Though the prevalence of SLC30A2 disease-causing variants is unclear, carrier screening may provide a unique opportunity to proactively identify females with known pathogenic SLC30A2 variants that would impart risk to their future breastfed children and breast milk recipients.
Carter et al. (Sun,) studied this question.