Acquired zinc deficiency in full-term newborns from decreased zinc content in breast milk

Zinc deficiency occurs in children when the demand for zinc exceeds its supply. Malnutrition, prematurity, total parenteral nutrition dependence, and burns increase the demand for zinc, whereas congenital malabsorption syndromes represent clinical situations where less zinc is supplied to the growing child. Clinical recognition of acral eczematous lesions, alopecia, and gastrointestinal tract symptoms in settings of the aforementioned medical history often lead to the diagnosis. Zinc deficiency in healthy, full-term, breast-fed infants can occur. The cause of these deficiencies has been attributed to decreased zinc levels in maternal breast milk. We present a case of acquired zinc deficiency in a healthy breast-fed infant, with a review of the English language literature of reported cases.     

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.     

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.     

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.     

Transient Zinc Deficiency in Two Full-term Breast-fed Siblings Associated with Low Maternal Breast Milk Zinc Concentration

Symptomatic zinc deficiency developed in an exclusively breast-fed, full-term infant. Her older brother had also developed zinc deficiency while being exclusively breast-fed. Breast milk zinc concentrations were low throughout lactation, and this inadequacy is the likely cause of the deficiency in both infants.     

Symptomatic zinc deficiency in breast-fed premature infants

We report two breast-fed premature infants who developed transient symptomatic zinc deficiency with scaly erythema of cheeks and napkin area, 9-13 weeks after birth. Serum zinc concentrations were 3.6 and 4.8 mumols/l, and the lesions healed rapidly in response to oral zinc supplements. Both mothers had low breast-milk zinc levels (2.3 and 3.2 mumols/l at 21 and 15 weeks respectively). The infants were both initially misdiagnosed as having eczema and infection. Premature infants are in negative zinc balance and though the additional factor of a low maternal breast milk zinc concentration may be necessary to provoke symptoms, rashes developing in such infants in the months following premature birth should raise the suspicion of zinc deficiency.     

Acquired zinc deficiency in two breast-fed mature infants

Zinc deficiency was diagnosed in a breast-fed mature infant and her sister. In both infants the characteristic dermatitis appeared on the face and buttocks around 10 weeks of age. It responded rapidly to zinc supplements. Their mother's serum zinc level was slightly low but her milk was found to be remarkably low in zinc. Oral zinc supplementation could correct only her serum zinc level but not her low breast milk zinc level. Therefore the mother's deficiency in the transfer process of zinc from serum to breast milk was suspected as a cause of the skin changes in her children. These cases indicate that even mature infants, who feed exclusively on mother's milk, run a risk to develop zinc deficiency, if the concentration of zinc in the breast milk is very low.     

Acquired acrodermatitis enteropathica secondary to alcoholism

Acrodermatitis enteropathica is a zinc deficiency disorder characterized by well-demarcated, erythematous, eczematous plaques in a periorificial and acral distribution. Hereditary and acquired forms have been described. We report a case of acquired acrodermatitis enteropathica secondary to alcoholism. Treatment of the underlying disorder and zinc replacement therapy resulted in rapid resolution of the condition.     

Transiente Zinkmangeldermatitis des Frühgeborenen

Zinc is an essential element and necessary for various cellular functions. Preterm infants may have a negative zinc balance and are therefore especially susceptible for symptomatic zinc deficiency. We report on a preterm child with distinct clinical manifestations of zinc deficiency confirmed by histology and laboratory analysis who quickly healed with oral zinc therapy.     

Acrodermatitis dysmetabolica in an infant with maple syrup urine disease

Acrodermatitis dysmetabolica (AD) is a rare, newly termed, and poorly understood disease that appears to be clinically similar to acrodermatitis enteropathica (AE). Both diseases are characterized by the triad of periorificial and acral dermatitis, diarrhoea, and alopecia. Unlike AE, which is caused by zinc deficiency, AD is caused by numerous metabolic disorders. One such disorder is maple syrup urine disease (MSUD), a genetic deficiency of branched chain α‐ketoacid dehydrogenase, the enzyme that degrades the branched‐chain amino acids (BCAAs) isoleucine, leucine and valine. Treatment involves restricting BCAAs to prevent accumulation. We report a case of an infant being treated for MSUD, who developed the triad of AE/AD after a period of poor BCAA formula intake. The child was found to have low isoleucine and normal zinc levels. Increasing the isoleucine dose improved the eruption, thus the diagnosis of AD secondary to isoleucine deficiency was made. This case emphasizes the importance of carefully balancing BCAA levels while treating MSUD, as deficiency can precipitate AD.     

Transient zinc deficiency syndrome in a breast-fed infant due to decreased zinc in breast milk (type II hypozincemia of infancy): A case report and review of the literature

Type II hypozincemia of infancy is a rare, hereditary zinc deficiency occurring in infants while exclusively on breast feeding. It is caused by defective transfer of zinc into breast milk. Only a few dozen cases have been reported. A 6-month-old, full-term, breast-fed female infant presented with a 3-week history of erythematous to dusky red papules and annular plaques over the perioral and diaper area as well as the digits. The eruption was accompanied by poor appetite and irritable crying. Serum zinc was low (4.896 μmol/L, normal = 10.71?18.36 μmol/L) in the patient but was normal in the mother. Interestingly, the zinc level in the breast milk was very low (2.142 μmol/L; normal postpartum zinc = 18.36 μmol/L at 6 months). Histopathology of a skin biopsy specimen showed spongiotic psoriasiform dermatitis with pallor of superficial keratinocytes, consistent with deficiency disease. With oral zinc sulfate supplement, her skin lesions improved significantly within 4 days. Type II hypozincemia needs to be differentiated from the classical hereditary acrodermatitis enteropathica, which typically develops symptoms after weaning because of poor intestinal absorption of zinc in the affected infants. Mutations in zinc transporter genes have been detected in SLC39A4 (Zip4) and SLC30A2 (ZnT2), respectively, in classical acrodermatitis enteropathica and type II hypozincemia. No mutation was found in these two genes in the present pedigree. Therefore, the genetic defect in our patient might involve other zinc transporter genes.     

Transient Zinc Deficiency in a Full-Term Breast-Fed Infant of Normal Birth Weight

A full-term male infant was seen at age 5 months with symptomatic zinc deficiency. He was breast fed and the mother's milk zinc levels were low. The infant responded to oral zinc supplements and has continued to be asymptomatic for 12 months after their withdrawal. This is the first report of transient zinc deficiency in an otherwise healthy, breast-fed, full-term infant of normal birth weight.     

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.     

Necrolytic acral erythema associated with hepatitis C: effective treatment with interferon alfa and zinc

BACKGROUND: Necrolytic acral erythema is a recently described necrolytic erythema that is unique in its exclusive acral location and strong association with hepatitis C. OBSERVATION: We report the first case of necrolytic acral erythema in the United States. The patient is a 43-year-old black woman who presented with a 4-year history of tender, flaccid blisters localized to the dorsal aspect of her feet. Serum zinc and glucagon levels were normal. Serum antibodies were positive for hepatitis C, and a liver biopsy specimen showed chronic hepatitis. She was successfully treated with interferon alfa-2b and zinc. We review all previously reported cases. CONCLUSIONS: Necrolytic acral erythema is a distinct entity. In a review of the literature, most patients were between 35 and 55 years of age, although 1 patient was 12 years old. Five of 8 patients were female. Four of 7 patients described previously were treated with variable success using oral zinc sulfate and amino acids, whereas 2 were successfully treated with interferon alfa. All patients were infected with hepatitis C. Necrolytic acral erythema appears to be a skin disorder linked to infection with hepatitis C virus that responds to treatment with interferon alfa and oral zinc.     

Acquired acrodermatitis enteropathica: case report of an atypical presentation

Acrodermatitis enteropathica (ADE) is a rare genetic or acquired disorder of hypozincemia. It can be caused by impaired intestinal absorption of zinc or by poor consumption of the mineral. It is characterized by skin lesions on acral and periorificial areas and may be associated to alopecia, diarrhea and increased frequency of infections. We present an atypical presentation of ADE in a 33-year-old women with a history of mental retardation and psoriasis that presented with lesions on the periorificial areas and extremities, and low plasma zinc levels.     

Acrodermatitis enteropathica-like syndrome secondary to branched-chain amino acid deficiency during treatment of maple syrup urine disease

INTRODUCTION: Clinical pictures resembling acrodermatitis enteropathica have been described in acquired zinc deficiency and deficiencies of other nutrients such as biotin, essential fatty acids and amino acids as well as biotin metabolism disorders. We describe the case of an infant with maple syrup urine disease who developed an acrodermatitis-like syndrome due to iatrogenic valine and isoleucine deficiency. CASE-REPORT: A diagnosis of maple syrup urine disease was made in a 5-month-old infant girl with severe neurologic disorders with extremely high levels of the three branched-chain amino acids (leucine, valine and isoleucine) in plasma and urine. Seven days after the start of therapy with a diet excluding these branched-chain amino acids, plasma isoleucine and valine concentrations were low while plasma leucine remained elevated. At the same time, a periorificial and acral dermatitis appeared together with diarrhea. Serum zinc concentrations were normal. A diagnosis of acrodermatitis enteropathica-like syndrome secondary to isoleucine and valine deficiency was suspected. Valine and isoleucine supplementation resulted in rapid resolution of the eruption. DISCUSSION: Several cases of acrodermatitis enteropathica-like eruptions resulting from therapeutic protein restriction diets have been described in infants with different aminoacidopathies. The accompanying dermatosis was associated with a raised plasma leucine/isoleucine ratio and/or isoleucine deficiency, or valine deficiency. While the exact pathogenesis of the skin lesions has not been established, these observations show that branched-chain amino acids are essential for normal growth and differentiation of keratinocytes. The essential role of isoleucine is further substantiated by the fact that its presence is critical in keratinocyte culture media, with growth arrest occurring upon its depletion.     

Acquired zinc deficiency acrodermatitis associated with nephrotic syndrome

Abstract:  We present a child with new-onset nephrotic syndrome, acrodermatitis, low serum zinc levels and decreased serum alkaline phosphatase. A diagnosis of acquired zinc deficiency acrodermatitis was made. Oral zinc supplementation led to rapid clinical resolution. The etiology of zinc deficiency in nephrotic syndrome remains unknown.     

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.     

Unique presentation of transient zinc deficiency from low maternal breast milk zinc levels

We report full‐term siblings with a unique clinical presentation of polycyclic papulosquamous plaques secondary to transient zinc deficiency due to low maternal breast milk zinc levels. We present this case to highlight this unique presentation of zinc deficiency in breastfed infants.