Symptomatic zinc deficiency in a breast-fed, premature infant

Hypozincemia and clinical features of acrodermatitis enteropathica developed in a breast-fed, premature infant at 6 months of age. Maternal breast milk zinc levels were normal at birth and at the time of appearance of zinc deficiency in the infant. Zinc supplementation administered orally resulted in rapid improvement. Seven premature infants with hypozincemia and transient symptomatic zinc deficiency have been previously described. In contrast with this case, the other infants received feedings with low zinc content.     

A Diagnostic Challenge: A Case of Acrodermatitis Enteropathica without Hypozincemia and with Maternal Milk of Low Zinc Level

Abstract: Acrodermatitis enteropathica is a rare and distinct form of zinc deficiency with a requirement of life‐long zinc supplementation and inherited in a recessive manner. Transient nutritional zinc deficiency is also a well known condition mimicking acrodermatitis enteropathica like skin changes in preterm and term infants who are generally breastfed with a low level of zinc containing milk. Here, a 4‐month‐old male, term and fully breastfed acrodermatitis enteropathica case without hypozincemia and with maternal milk of low zinc level is presented.     

Acrodermatitis enteropathica with anorexia nervosa

Acrodermatitis enteropathica is a rare hereditary or acquired disorder of hypozincemia. It is characterized by acral and periorificial dermatitis, alopecia, diarrhea and growth retardation. Anorexia nervosa is characterized by low body weight, body image distortion with an obsessive fear and is also associated with various cutaneous findings including acrodermatitis enteropathica. We report a 37‐year‐old female with acrodermatitis enteropathica showing acquired zinc deficiency with anorexia nervosa.     

A novel homozygous mutation p.E88K in maternal SLC30A2 gene as a cause of transient neonatal zinc deficiency

The SLC30A2 gene encodes zinc transporter ZnT2, which is indispensable for the transport of zinc into the breast milk in the mammary gland. Transient neonatal zinc deficiency (TNZD) is caused by a mutation in the maternal SLC30A2 gene and has a clinical presentation similar to that of acrodermatitis enteropathica (AE). We described the case of a Chinese infant who presented with AE-like lesions 10 days after birth. Sanger sequencing of the AE-causing gene SLC39A4 revealed no mutations in genomic DNA from the infant, excluding the possibility of AE. Detection of the mother's breast milk showed a significantly lower zinc level. Thus, SLC30A2 sequencing was performed on her genomic DNA and a previously unreported homozygous c.262G > A (p.E88K) mutation was disclosed. Functional analysis suggested the novel mutation could lead to a strong disruption of zinc secretion, which indicated a complete loss of function in the ZnT2 protein. We finally diagnosed the infant with TNZD. To the best of our knowledge, this is the first case of TNZD caused by a homozygous mutation in the maternal SLC30A2 gene. Compared to the heterozygous condition, a homozygous mutation seems to result in a more significant decrease in zinc secretion and a more rapid onset of TNZD.     

Transient symptomatic zinc deficiency in a breast-fed preterm infant

Abstract:  Transient, symptomatic zinc deficiency in breast-fed, low-birthweight infants is a rare, but probably underrecognized disorder hallmarked by periorificial and acral dermatitis. Unlike in acrodermatitis enteropathica, symptoms disappear when nursing ends. We report a breast-fed, preterm infant with demarcated, erythematous, and exudative patches with overlying crusts on the perioral, perianal, and acral areas. Laboratory investigations revealed lowered zinc levels in the infant's serum, but normal levels in his mother's milk. Oral zinc supplementation resulted in total clearing of skin lesions within 4 weeks. Our patient's presentation illustrates the importance of zinc in rapidly growing preterm infants and aims to stimulate awareness for this disorder. Symptomatic zinc deficiency can be easily diagnosed by careful examination and effectively treated with oral zinc substitution.     

Transient Neonatal Zinc Deficiency Due to a New Autosomal Dominant Mutation in Gene SLC30A2 (ZnT‐2)

Transient neonatal zinc deficiency (TNZD) has a clinical presentation similar to that of acrodermatitis enteropathica but is caused by a low zinc concentration in maternal breast milk. TNZD becomes clinically evident during breastfeeding and is resolved by weaning and the introduction of complementary nutrition. We present a 4‐month‐old girl with TNZD due to a new autosomal dominant mutation (663delC) in the maternal SLC30A2 gene not previously described in the literature.     

Transient zinc deficiency in a breast-fed premature infant

Symptomatic zinc deficiency developed in a breast-fed premature male infant of 31 weeks gestation. At 13 weeks of age he presented with diarrhoea, irritability and an eruption identical to acrodermatitis enteropathica. Breast milk zinc concentrations were low. His course was complicated by milk protein intolerance. After 7 weeks, zinc supplementation was ceased without recurrence of disease.     

Acrodermatitis enteropathica in full-term breast-fed infant

BACKGROUND: Acrodermatitis enteropathica is a rare autosomal recessive disorder, caused by impaired absorption of zinc from the gastrointestinal tract. Symptoms of acrodermatitis enteropathica occur within the first few months after birth and tend to appear shortly after discontinuation of breast-feeding. We report a breast-fed infant with acrodermatitis enteropathica. CASE REPORT: A full term, 4-month-old girl, consulted in dermatologic department for persistent and refractory anogenital lesions since the age of 1 month, with progressive erythematous, vesiculous and squamous lesions, sometimes erosive in a peri orificial and acral pattern. She was calm and healthy baby. She was breast feeding. The diagnosis of acrodermatitis enteropathica was confirmed by decreased plasma zinc level (14 microg/100 ml). Breast milk zinc levels was low (46 microg/100 ml), as plasma zinc level of the mother (94 microg/100 ml). A genetic study showed that she was homozygous for the mutation, whereas her brother and parents were heterozygous. She was given zinc sulphate, and her condition has improved significantly. DISCUSSION: Acrodermatitis enteropathica is characterized by a characteristic clinical feature and the diagnosis is confirmed by decreased plasma zinc level. Acrodermatitis enteropathica in exclusively breast fed infant is rare, it was essentially reported in premature babies. Our case report is particular because it's concerning a full-term breast-fed infant, with zinc deficiency in breast milk and mother's decreased plasma zinc level.     

AN ACQUIRED FORM OF ACRODERMATITIS ENTEROPATHICA DUE TO LONGTERM LACTOSE-FREE MILK ALIMENTATION

A 4-month-old boy, fed on lactose-free milk for the treatment of intractable diarrhea for about 3 months, developed acrodermatitis enteropathica-like skin lesions. All the symptoms dramatically disappeared 2 weeks after switching from this milk to a general cow's milk formula, and his low serum zinc level also rapidly returned to normal. The zinc deficiency seen in this case was presumed to be closely related to longterm lactose-free milk alimentation. Acrodermatitis enteropathica, a human zinc deficiency, should be classified into two types, hereditary and acquired. The latter form can develop from intravenous hyperalimentation, longterm lactose-free milk alimentation and longterm penicillamine administration.     

Acrodermatitis enteropathica: an uncommon differential diagnosis in childhood – first description of a new sequence variant

An 11‐month‐old boy was brought to our clinic with superinfected, sharply‐defined, symmetrical, erythematous macules and vesicles, some with yellowish‐brownish crusts, on the cheeks, fingers, and in the diaper region. The suspected impetigo contagiosa had failed to respond to both topical antiseptic therapy and systemic antibiotics. Because of the unusual clinical picture and course, we measured the serum zinc level. A significantly reduced level of 2 μmol/l (normal range 9.2–18.4 μmol/l) was identified. Initial skin lesions had appeared one week after weaning (5th week after birth). Since the age of 8 months the infant had also had recurrent diarrhea. Two weeks after zinc‐histidine substitution, the diarrhea ceased and skin lesions slowly disappeared. Molecular genetic testing for the SLC39A4 (zinc transporter) gene revealed compound heterozygosity for the previously unidentified mutations c.1465_1474+4del (p.?) and c.295G>A (p.Ala99Thr). The parents are healthy heterozygous gene carriers. The same compound heterozygosity was later detected in the newborn brother of our patient shortly after birth. A zinc deficiency could therefore be identified and treated before symptoms occurred. The inherited autosomal recessive zinc transporter deficiency is termed acrodermatitis enteropathica. Lifelong zinc substitution is recommended. A differential diagnosis can be difficult because bacterial and fungal superinfection is common in zinc deficiency. Precise diagnosis requires testing family members for the gene.     

Acrodermatitis enteropathica: a novel SLC39A4 gene mutation found in a patient with an early-onset

We report the case of a 3-month-old full-term, breast-fed infant with clinical and laboratorial findings consistent with acrodermatitis enteropathica. In addition, the mother had low zinc levels in her breast milk. Mutation analysis revealed a novel insertion in the SLC39A4 gene.     

Cutaneous manifestations observed during prolonged intravenous feeding: 3 cases. Review of the literature (author's transl)]

3 patients (one infant and two adults) in prolonged intravenous feeding for digestive diseases developed cutaneous symptoms resembling acrodermatitis enteropathica. Essential fatty acid and hypozincemia (in 2 of 3 cases) are found. The dermatitis disappeared slowly with oral alimentation in 2 cases, and in a few days in the third one, with oral zinc sulfate. Review of literature shows that dermatitis occurring during prolonged intravenous feeding is attributed to essential fatty acid, zinc, or less often amino acid, deficiency. But resemblance of dermatitis with acrodermatitis enteropathica in most cases, high frequency of hypozincemia, and dramatic effects of treatment with zinc salts allow to think, that zinc is a key factor. Nevertheless, it is necessary to study simultaneously those different parameters and also vitamins A, E and B to conclude whether it exists or not many deficiencies (related or not) as an etiologic factor for cutaneous symptoms.     

Novel SLC39A4 mutations in acrodermatitis enteropathica

Acrodermatitis enteropathica is an autosomal recessive disease characterized by skin involvement due to defective intestinal zinc absorption. Usually, the skin lesions include erythema, erosions, and small blisters in perioral, perianal regions, and hands and feet, which develop soon after weaning from the breast. The acrodermatitis enteropathica gene has been localized to chromosomal region 8q24.3 and subsequently the SLC39A4 gene has been disclosed as the acrodermatitis enteropathica gene. SLC39A4 mutations have been demonstrated in several acrodermatitis enteropathica families, and in this study we have examined two Japanese acrodermatitis enteropathica families for SLC39A4 mutations. The mutation detection strategy consisted of polymerase chain reaction amplification of all 12 exons and flanking intronic sequences, followed by direct nucleotide sequencing. It revealed three novel mutations, 1017ins53, which creates a premature termination codon, and two mis-sense mutations, R95C and Q303H.     

Transient zinc deficiency in a breast fed, premature infant

A 5-month-old-male was observed for an acrodermatitis enteropathica-like skin eruption evolving since the second month. He was born prematurely at 27 weeks and his neonatal course was complicated by respiratory distress syndrome, sepsis and subependimary haemorrhage. He was fed with breast milk from the second day of life, fortified initially by a protein mineral supplement containing zinc. Serum zinc concentration was low and the mother's serum and milk had normal zinc values. Oral zinc supplementation was introduced with total clearing after three weeks. Treatment lasted 22 months and no relapse was observed after discontinuation. Premature infants have a negative zinc balance mainly secondary to inadequate stores and high requirements. The relevance of these factors is illustrated by the present case where symptomatic zinc deficiency developed despite maternal milk with normal zinc content and a milk fortifier containing zinc.     

一例锌缺乏患者的SLC39A4基因突变检测并文献复习

目的：检测1例锌缺乏患者SLC39A4基因的突变,并对国内外报道的肠病性肢端皮炎和获得性锌缺乏的文献进行回顾性分析。方法：提取患者外周血DNA,采用聚合酶链式反应(Polymerase Chain Reaction, PCR)和DNA直接测序方法检测患者SLC39A4基因的突变。结果：在SLC39A4基因上没有检测出致病突变。文献检索共检索锌缺乏患者139例,结合本院1例,共140例。其中肠病性肢端皮炎患者有84例,获得性锌缺乏患者有56例。肠病性肢端皮炎患者中进行SLC39A4检测的有39例,突变检出率为100%,其中预后需要长期补锌治疗的34例（87.2%）。获得性锌缺乏患者中进行SLC39A4基因检测的有19例,突变检出率为0%,均不需要长期补锌治疗。结论：肠病性肢端皮炎与SLC39A4基因的突变有关,而获得性锌缺乏的发病未发现与SLC39A4基因的突变相关,SLC39A4基因检测对肠病性肢端皮炎和获得性锌缺乏的鉴别有重要意义。     

Self-Limiting Acrodermatitis Enteropathica

A variant of acrodermatitis enteropathica is described that has its onset before weaning and clears when the child starts its normal solid diet. A pedigree with three interrelated families is reported where 10 children were afflicted with this variant. They had symptoms of hypozincemia for a brief period during infancy. At the time of this study, they were symptom-free and their serum zinc levels were found to be within normal limits. The term "self-limiting acrodermatitis enteropathica" is proposed for the variant. In one lactating mother, the mammary zinc secretion was determined and was found to be deficient and unresponsive to oral zinc supplements. The possible mode of inheritance is also discussed.     

Acrodermatitis enteropathica

A 13-year-old girl presented with a history of red scaly plaques involving the chest, arms and legs beginning in infancy. Punch biopsy revealed psoriasiform hyperplasia and pallor of the epidermis. The patient's serum zinc level was 36 mug/dl [nl. 66-144 mug/dl]. A diagnosis of acrodermatitis enteropathica was established and the patient responded well to zinc replacement therapy. Acrodermatitis enteropathica is a rare autosomal recessive disorder caused by mutations in SLC39A4, which encodes the tissue-specific zinc transporter ZIP4.     

Hereditary zinc deficiency (Adema disease) in cattle, an animal parallel to acrodermatitis enteropathica.

Adema disease and acrodermatitis enteropathica, two parallel syndromes in calves of Friesian descent and in man, are described. Both are congenital zinc deficiency disorders with a lethal course if left untreated. Complete recovery follows oral zinc therapy. Symptoms and findings are set out in Table I. Diseased calves may serve as animal models for further studies on acrodermatitis enteropathica and the biological role of zinc.     

Zinc and skin: an update

The essential trace element zinc (Zn) plays a key role in the development, differentiation and growth of various human tissues. Zinc homeostasis is primarily regulated by two zinc transporter families (solute‐linked carrier families, SLC). Disturbances in zinc metabolism may give rise to disorders that typically manifest themselves on the skin. An autosomal recessive zinc deficiency disorder, acrodermatitis enteropathica is caused by a mutation in the gene coding for the ZIP4 transporter. Due to intestinal malabsorption, affected infants develop clinical signs and symptoms shortly after weaning. Acquired zinc deficiency is a rare but underdiagnosed disorder associated with various etiologies and variable clinical manifestations. Depending on the patient's age, a multitude of causes have to be considered. Given the characteristic periorificial and acral lesions, the clinical diagnosis is usually made by dermatologists. Laboratory confirmation includes measurement of plasma zinc levels and – as a supplementary measure – zinc‐dependent enzymes such as alkaline phosphatase. Oral zinc replacement therapy frequently leads to clinical remission within a few days. Depending on the cause, disease management should include cooperation with pediatricians and gastroenterologists in order to guarantee optimal patient care.