Infants and children develop zinc deficiency when the demand exceeds its supply. Inherited zinc deficiency, known as AE, has an incidence rate of 1/500,000 [
10]. The condition is due to the
SLC39A4 gene mutations, which limits the zinc absorption of the ZIP4 transporter in the small intestines, resulting in insufficient zinc absorption in the duodenum and jejunum [
11]. Statistics have shown that the prevalent high-frequency mutations of AE are located in exons 9, 3 and 5, and the clinical phenotypes vary with different exron mutations [
12]. Periorificial dermatitis, alopecia and diarrhoea are the characteristic symptoms of AE, but these three symptoms simultaneously occur in only 20% of patients [
13]. The systemic features also encompass irritability, lethargy, anorexia, growth impairment, anemia, neuropsychiatric disorders, immunological aberrations, and ocular anomalies such as conjunctivitis, blepharitis, corneal opacities, and photophobia [
14].
TSZD, the acquired form, is a self-limited disease primarily observed in exclusively or partially breastfed premature and low birth weight infants[
15‐
17,
8], but it has also been reported in full-term infants [
18‐
20,
7]. Compared to AE, the etiologies of TSZD are more diverse, including preterm, low birth weight, PN history andothers. Preterm and low birth weight infantsare more susceptible to developing zinc deficiency than full-term infants due to their inadequate zinc stores, compromised ability to absorb zinc from the intestine and increased zinc requirements during catch-up growth [
21]. PN is considered a risk factor of acquired zinc deficiency in numerousreports, associated with a lack of awareness and inadequate management of the importance of trace elements in PN, leading to an iatrogenic TSZD [
22,
23]. In the case we report, the simultaneous presence of aforementioned three risk factors -preterm, low birth weight, and a history of PN- result in severe zinc deficiency shortly after birth. It is worth noting that an increasing number of case reports on TSZD in full-term infants have been documented in recent years. This suggests that besides factors such as preterm birth, other mechanisms are involved in the pathogenesis of TSZD. Studies demonstrate that
SLC30A2 gene mutations of nusing monthers lead to low zinc levels in breast milk, which serves as one of the causes of TSZD in full-term infants who areexclusively or partially breastfed [
6].
SLC30A2 gene mutations could result in dysfunction of the zinc transporter 2 (ZnT2), which is responsible for zinc secretion into breast milk [
24,
25]. Unfortunately, one limitation of this case is that we are unable to assess the zinc levels in the mother’s milk, due to the unique customs of the ethnic minorities involved. We did not further encourage the mother to undergo testing for the
SLC30A2 gene in consideration of the financial challenges faced by the family. The reason is that the absence of any amelioration in rash or diarrhea symptoms during the two-week period of breastfeeding discontinuation in this case led us to presume that the zinc levels in breast milk are not low. Provided that the mother’s
SLC30A2 gene mutations result in decreased zinc levels in breast milk, and subsequently leads to insufficient zinc intake in exclusively breastfed or breastfed infants exhibiting zinc deficiency symptoms, it is anticipated that the symptoms will experience significant improvement following the cessation of breastfeeding. However, this is not the case. Currently, the exact prevalence of TSZD remains obscure, potentially underestimated. In a Chinese research study, 18 children were initially diagnosed with AE based on the typical skin lesions and low blood zinc levels. However, no mutation was detected in
SLC39A4 sequencing outcomes. In conjunction with the clinical manifestations, strong response to zinc supplementation, and absence of recurrence following cessation of zinc therapy, these patients were ultimately diagnosed with TSZD [
26]. Thus, it can be seen that the recognition of TSZD is insufficient and the important value of
SLC39A4 gene test in the differential diagnosis between TSZD and AE is overlooked. Although the clinical manifestations of TSZD and AE are alike, there are distinctions in the onset and prognosis. TSZD typically occurs during breastfeeding, necessitates only short-time zinc supplementation and dosenot recur after stopping zinc treatment.Conversely, AE predominantly presents after weaning, necessitates lifelong zinc supplementation, and is susceptible to relapse when zinc supplementation isceased. It is interesting to note that there is currently no literature on the definite time of zinc supplementation for childern with TSZD. It is observed that the treatment duration reported in the literature ranged from less than a month to over 22 months [
27,
28]. Therefore, we deem that the short-term zinc supplementation of TSZD is a relative concept in the context of lifelong zinc supplementation of AE.
Collectively, we report a case with AE-like skin lesions. Based on a comprehensive evaluation of characteristics such as preterm birth, low birth weight, a history of PN, hypozincemia, the absence of SLC39A4 gene mutations, a marked response to zinc therapy, and the absence of recurrence following the withdrawal of zinc supplementation, the premature infant was ultimately diagnosed with TSZD. By reporting this case, we emphasize the challenges associated with distinguishing TSZD from AE, and recommend that routine testing for the SLC39A4 gene be performed for patients with AE-like dermatitis. When the SLC39A4 gene test is not conducted, we underscore the necessity of a long-term follow-up to observe whether zinc deficiency-related symptoms reappeared after zinc discontinuation, in order to draw definitive diagnostic conclusions.