Letter - Clinical
Transient neonatal zinc deficiency or acrodermatitis enteropathica?
Luciane Francisca Fernandes Botelho
, Selma Hélène, Carolina Gonçalves Contin Proença, Silvia Assumpção Soutto Mayor
Autor para correspondência
Dermatology Clinic, Hospital da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil
Lido
2026
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"tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">Dear Editor,</span>" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "763" "paginaFinal" => "765" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Luciane Francisca Fernandes Botelho, Selma Hélène, Carolina Gonçalves Contin Proença, Silvia Assumpção Soutto Mayor" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Luciane Francisca Fernandes" "apellidos" => "Botelho" "email" => array:1 [ 0 => "lucianebotelho@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Selma" "apellidos" => "Hélène" ] 2 => array:2 [ "nombre" => "Carolina Gonçalves Contin" "apellidos" => "Proença" ] 3 => array:2 [ "nombre" => "Silvia Assumpção Soutto" "apellidos" => "Mayor" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Dermatology Clinic, Hospital da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1403 "Ancho" => 1505 "Tamanyo" => 231499 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0050" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Erythematous-desquamative lesions in the perioral, perinasal, glabella and genital regions.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A five-month-old male patient presented with erythematous-desquamative lesions of two months duration, initially in the perioral region, which progressed to the following regions: acral, perinasal, genital, shoulders and occipital with associated alopecia (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). There was no diarrhea or systemic involvement. He had been treated with antifungals, topical corticosteroids and systemic antibiotics in another service without improvement. A clinical hypothesis of acrodermatitis enteropathica <span class="elsevierStyleItalic">versus</span> transient neonatal zinc deficiency (TNZD) was made and serum zinc and alkaline phosphatase measurements were requested, the results of which showed no alterations. His personal history showed he had been preterm (34 weeks) and exclusively breastfed. Zinc measurement in breast milk could not be performed, as it is not a commercially available test in Brazil.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Given the characteristic clinical picture and the extent of the skin lesions, oral zinc supplementation was started at a dose of 3<span class="elsevierStyleHsp" style=""></span>mg/kg/day. After three weeks of supplementation, the patient significantly improved (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), confirming the diagnosis of zinc deficiency, despite normal serum zinc levels. The patient continued to be monitored and at the age of one year and three months, complete exome sequencing was performed, which identified a mutation in the SLC30A2 gene. The mother did not undergo the genetic test, but the patient probably inherited the mutation from the mother who produced milk with a low concentration of zinc. The authors concluded that it was a case of TNZD and supplementation was suspended. The patient showed no recurrence of lesions.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Zinc acts on cell development, differentiation and growth.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Zinc deficiency can be either genetic or acquired. The genetic forms are autosomal recessive, known classically as acrodermatitis enteropathica, or autosomal dominant called TNZD.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In acrodermatitis enteropathica, the mutation occurs in the SLC39A4 gene, and the incidence of this mutation is estimated at 1/500,000 children without predilection for gender or ethnicity. The SLC39A4 gene encodes the ZIP4 protein, present in intestinal enterocytes, responsible for zinc absorption.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> TNZD occurs in children who are exclusively breastfed, due to the low concentration of zinc in breast milk, resulting from the maternal mutation in the SLC30A2 gene. This gene encodes a zinc transporter called ZNT2 present in mammary gland cells and responsible for transporting zinc into breast milk.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> depicts the main differences between acrodermatitis enteropathica and TNZD.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The acquired forms of zinc deficiency may be due to preterm birth, zinc-deficient parenteral nutrition and intestinal malabsorption syndromes.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The clinical picture of the genetic and acquired forms is similar; in both forms, the patients show erythematous-desquamative plaques, and vesicles, bullae and pustules may appear in the periorificial and acral regions. Other manifestations include alopecia, diarrhea, angular cheilitis, paronychia, growth retardation, neurological deficit, difficulty in healing, anemia, photophobia, hypogeusia, anorexia, pubertal delay, and hypogonadism.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,5</span></a> The symptoms of classic acrodermatitis enteropathica usually appear when breastfeeding is stopped, as breast milk is rich in bioavailable zinc; however, in preterm infants with a high zinc demand, symptoms may appear during breastfeeding.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Among the differential diagnoses, we must consider biotin deficiency, fungal infections, seborrheic dermatitis, psoriasis, Langerhans cell histiocytosis, and contact dermatitis.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The present case was a diagnostic challenge, as serum zinc levels were normal, but according to the literature, there are reports of acrodermatitis enteropathica with normal serum zinc levels.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7–9</span></a> This paradox is, in part, a result of the homeostasis of plasma zinc, which comprises only 0.1% of total body zinc reserves. Therefore, accurately measuring zinc levels in the body is difficult. A reduced serum level of alkaline phosphatase, a zinc-dependent metalloenzyme, may help in the diagnosis.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">With adequate treatment, changes resulting from zinc deficiency resolve without sequelae, but prolonged periods of deficiency can permanently affect growth and neurological development. Zinc supplementation in children with a transient deficiency should be carried out with 1<span class="elsevierStyleHsp" style=""></span>mg/kg/day and patients with acrodermatitis enteropathica should receive 3<span class="elsevierStyleHsp" style=""></span>mg/kg/day of supplementation.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In acrodermatitis enteropathica, the supplementation must be maintained throughout life, whereas in TNZD, the supplementation can be suspended after the period of exclusive breastfeeding.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">This case report shows the importance of genetic testing in the diagnosis of zinc deficiency in infants, since regardless of the etiology, the clinical manifestations can be identical.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0055" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors' contributions</span><p id="par0060" class="elsevierStylePara elsevierViewall">Luciane Francisca Fernandes Botelho: Design and planning of the study; drafting and editing of the manuscript; data survey, collection, analysis and interpretation of data; critical review of the literature; approval of the final version of the manuscript.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Selma Hélène: Analysis and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied case; critical review of the literature; approval of the final version of the manuscript.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Carolina Gonçalves Contin Proença: Intellectual participation in the propaedeutic and/or therapeutic conduct of the studied case; critical review of the literature; critical review of the manuscript; approval of the final version of the manuscript.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Silvia Assumpção Soutto Mayor: Design and planning of the study; analysis and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied case; critical review of the literature; critical review of the manuscript; approval of the final version of the manuscript.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Financial support" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Authors' contributions" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-07-02" "fechaAceptado" => "2023-08-22" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Hospital da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil.</p>" ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1403 "Ancho" => 1505 "Tamanyo" => 231499 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0050" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Erythematous-desquamative lesions in the perioral, perinasal, glabella and genital regions.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1375 "Ancho" => 1505 "Tamanyo" => 222157 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0055" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Three weeks after zinc supplementation, the patient showed significant improvement.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0060" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Transient neonatal zinc deficiency \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Acrodermatitis enteropathica \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Genetic mutation and inheritance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SLC30A2, autosomal dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SLC39A4, autosomal recessive \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moment of clinical presentation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">It occurs in the first months of life when the child is exclusively breastfeeding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">It usually occurs after breastfeeding discontinuation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serum zinc measurement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reduced, rarely normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reduced, rarely normal \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Zinc measurement in breast milk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reduced \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Normal \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Maternal serum zinc measurement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Normal \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Need for zinc supplementation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Only during exclusive breastfeeding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Throughout life \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3652815.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Characteristics of transient neonatal zinc deficiency and acrodermatitis enteropathica.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Zinc and skin disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Y. 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