Dermatology Online Journal

Symptomatic zinc deficiency in a full-term breast-fed infant
Sambasiviah C Murthy MD, Malleshappa M Udagani MD DVD, Ashok V Badakali MD, Bhuvaneshwari C Yelameli MD
Dermatology Online Journal 16 (6): 3

Dermatology and Venereology Department, Vijayanagara Institute of Medical Sciences, Bellary, S. N. Medical College, Bagalkot and Department of Pediatrics, S. N. Medical College, Bagalkot, Karnataka. chidumurthy@rediffmail.com

---

Abstract

A nine-month-old female infant presented with an eruption over her face, perineal region, and upper and lower limbs. She had sparse hair growth and diarrhea. Clinical features and investigations were suggestive of hypozincemia. Therapy with zinc and weaning from breastfeeding led to resolution of the condition, confirming a diagnosis of hypozincemia type-II. Recently, a mutation in the zinc transporter gene SLC30A2 (ZnT-2), identified in the mothers of infants suffering from this disorder, is implicated as the cause. This report highlights the occurrence of hypozincemia among a population at risk, consisting of infants who are exclusively breast-fed for a prolonged period.

---

Introduction

Zinc is an essential trace element required for immune function, growth, reproduction, and antioxidant activities. Zinc deficiency may be hereditary or non-hereditary. Both forms have similar clinical manifestations. This important nutritional disorder of children predominantly affects the skin, hair, nails, and the gastrointestinal system [1, 2]. It presents with distinctive clinical manifestations. We report a case of type II hypozincemia in an exclusively breast-fed infant.

Case report

Figure 1	Figure 2
Figure 1. Erosions and crusting in the perioral region Figure 2. Lesions involving perineum, thighs, knees, and dorsa of feet

A nine-month-old female infant, an only child, born to non-consanguineous parents, presented with a 4-month history of a cutaneous eruption over her face, upper limbs, lower limbs, and perineum. She was irritable and had diarrhea intermittently. The child had been exclusively breast-fed. She had been treated with many topical and systemic medications without improvement. A cutaneous examination showed extensive, erosive, eczematous crusted plaques over the perioral region, perineum extending on to thighs and gluteal region, knees, elbows, and the dorsa of hands and feet. The rest of the cutaneous and mucosal examination revealed no abnormalities.

Figure 3
Figure 3. Complete resolution after treatment

Her routine hematological and urine laboratory tests were normal. Stool examination, blood urea, serum creatinine, and liver function tests were normal except for a mild decrease in alkaline phosphatase levels. VDRL and HIV serologies were negative. Examination of scalp hair under the light microscope did not reveal any abnormalities. Zinc level in the serum of the child was 45 micrograms/dl (normal 70-120 micrograms/dl) and in maternal breast milk was 7 micrograms/L (normal 11-12 micrograms/L). A diagnosis of hypozincemia in infancy was made. The child was started on elemental zinc orally at 2 mg/kg/day and was gradually weaned from breastfeeding. A dramatic improvement was observed within 48 hours, with the disappearance of irritability and diarrhea followed by healing of cutaneous lesions in ten days. Zinc supplementation was continued for ten days and stopped. No clinical recurrences were seen during a follow-up period of two years.

Discussion

The term acrodermatitis enteropathica (AE) is used for all patients with acral dermatitis related to zinc deficiency, although it should be strictly confined to hereditary forms [1]. Acrodermatitis enteropathica is characterized by the triad of dermatitis, diarrhea, and alopecia; the complete triad is seen in only 20 percent of patients [2].

Hypozincemia in infancy is divided into three types [3]. Type I is characterized by an inherent defect in the absorption of zinc from the gut, i.e., classical AE. Type II occurs because of defective secretion of zinc in mother’s milk. Type III develops in preterm infants who are put on prolonged parenteral alimentation deficient in zinc. Classical AE is inherited in an autosomal recessive pattern, whereas type II hypozincemia is reported to have an autosomal recessive or sex-linked inheritance [3].

In human beings, two gene families of zinc transporters, ZnT (SLC30A) and Zip (SLC39A), with opposite roles in cellular zinc homeostasis, have been identified [4]. In classical AE (type I), the genetic defect has been mapped to 8q24 and the defective gene is identified as SLC39A4, which encodes the zinc transporter Zip4. Zip4, a tissue-specific zinc-regulated transporter is abundantly expressed in enterocytes and allows absorption of dietary zinc in the small intestine. Zinc deficiency causes increased expression of Zip4 whereas zinc supplementation causes decreased expression [4, 5].

Our case belonged to hypozincemia type II because the child developed signs of zinc deficiency when exclusively breastfed and improved on therapy with zinc and weaning. In this type of deficiency, the optimal transport of zinc into the breast milk is defective. There is a decrease in the breast milk zinc level, despite normal serum zinc levels in the mother [3]. Zimmerman et al. [6] hypothesized that the problem is due to the abnormality of a zinc binding ligand in the breast milk. Studies on the lethal milk mouse with low breast milk zinc levels have shown an autosomal recessive inheritance with a defect in the ZnT4 gene [4, 5].

However, in human beings, it was found that a defect in ZnT4 was not responsible [7]. Recently, a mis-sense mutation (substitution of a conserved histidine at amino acid 54 with arginine, H54R) in the zinc transporter gene SLC30A2 (ZnT-2) has been identified as a cause for defective transfer of zinc from serum to breast milk. This results in transient neonatal zinc deficiency that does not correct with maternal zinc supplementation [8]. The problem may also be enhanced by marginal zinc deficiency in mothers, who have increased demands for zinc during pregnancy and lactation [1]. In classical AE, patients usually develop manifestations after weaning from breastfeeding and require life-long zinc supplementation.

The characteristic distribution of the dermatitis over face, hands, feet and anogenital areas is recognized as a pathognomonic cutaneous marker for zinc deficiency. The cutaneous lesions are psoriasiform or annular, erythematous, scaly, and crusted plaques. Vesiculobullous, pustular and erosive lesions may be found. Stomatitis, apathy, irritability, growth retardation, failure to thrive, hair loss, and delayed wound healing may be present. Delayed puberty and hypogonadism can occur in males with long-tem zinc deficiency. Ocular involvement may occur [2]. Clinically, other conditions such as biotin deficiency, essential fatty acid deficiency, methylmalonic aciduria, aminoacidopathies, organic acidemias, have to be considered, especially if the lesions do not respond to zinc or relapse or recur frequently [9].

Histopathology of skin lesions is non-specific and reveals confluent parakeratosis, psoriasiform epidermal hyperplasia, pallor of the upper part of the epidermis due to intracellular edema, focal dyskeratosis, and diminution/absence of granular layer in the epidermis [2, 4, 5]. Fully developed “necrolysis” may be seen. The term necrolysis refers to cytoplasmic pallor, vacuolization, ballooning degeneration, and subsequent confluent necrosis of kerationocytes within the superficial stratum spinosum and stratum granulosm. The affected kerationocytes often have pyknotic nuclei. Necrolysis may also be seen in pellagra and glucagonoma-associated necrolytic migratory erythema [4].

It is important to differentiate type II hypozincemia from classical AE because the treatment and prognosis varies. If it is difficult to prove zinc deficiency because of lack of testing facilities or other reasons, a reliable method is to give a therapeutic trial of zinc [10]. In zinc-deficiency states like classical AE or transient neonatal zinc-deficiency, zinc supplementation therapy should be started at 2-3 mg/kg/day of elemental zinc [4, 11]. In deficiency dermatitis caused by low dietary zinc, treatment with elemental zinc supplementation, 0.5-1 mg/kg/day is recommended [4, 10].

Oral zinc supplements are available as sulfate, acetate, gluconate or citrate salts. The amount of elemental zinc available in each preparation can vary depending on the degree of hydration of the complex. The amount of elemental zinc is commonly listed on the product label as the zinc equivalent [10]. The gluconate comes in a 10 mg pill, equivalent to 1.4 mg elemental zinc, sulfate comes as a 220 mg capsule equivalent to 50 mg elemental zinc, and zinc sulfate monohydrate comes in 137.5 mg capsules equivalent to 50 mg elemental zinc. Recently, a gluconate liquid formulation supplying 20 mg elemental zinc per 5 ml is available.

Typically, clinical improvement is seen very rapidly, within days to weeks, before a significant change in serum zinc levels [4]. There is rapid improvement of diarrhea within 24 hours and the erosive skin lesions heal within 1 to 2 weeks of zinc therapy without additional topical therapy [1, 11].

Serum or plasma zinc levels and zinc-dependent enzyme levels (e.g. alkaline phosphatase) should be monitored every 3 to 6 months and the dose of zinc sulfate should be adjusted accordingly. Patients may require a higher or lower dose than 2-3 mg/kg/day of zinc to normalize their genetic defect [4]. Zinc supplementation can lower blood copper levels, by reducing copper absorption and this should periodically be monitored [4, 10]. Zinc therapy can cause gastric irritation with nausea, vomiting and gastric hemorrhage. Large accidental overdoses may cause multisystem organ failure [4].

Exclusive breastfeeding and delayed weaning is being practized in many parts of rural India. This report highlights the occurrence of hypozincemia in this population. Awareness among the treating physicians, early diagnosis, and proper treatment will prevent prolonged morbidity and complications.

References

1. Neldner KH. Acrodermatitis enteropathica and other zinc deficiency disorders. In:Freedberg IM, Eisen AZ, Wolff K, et. al, editors, Fitzpatrick’s dermatology in General Medicine. 6th ed. New York:McGraw-Hill; 2003. pp 1412-8.

2. Kaur S, Thami GP, Kanwar AJ. Acrodermatitis Enteropathica in a full-term breast-fed infant. Indian J Pediatr 2002; 69: 631-3. [PubMed]

3. Sharma NL, Sharma RC, Gupta KR, Sharma RP, Mahajan VK. Hypozincemia in infancy. Indian J Dermatol Venereol Leprol 1985, 51: 256-60.

4. Maverakis E, Fung MA, Lynch PJ, Draznin M, Michael DJ, Ruben B, Fazel N. Acrodermatitis enteropathica and an overview of zinc metabolism. J Am Acad Dermatol 2007; 56:116-24. [PubMed]

5. Maverakis E, Lynch PJ, Fazel N. Acrodermatitis enteropathica. Dermatol Online J 2007; 13(3):11. [PubMed]

6. Zimmerman AW, Hambidge M, Lepow ML, Greenberg RD, Stover ML, Casey CE. Acrodermatitis in breast fed premature infants: evidence for a defect of mammary zinc secretion. Pediatrics 1982; 69: 176-83. [PubMed]

7. Michalczyk A, Varigos G, Catto-Smith A, Blomeley RC, Ackland ML. Analysis of zinc transporter hZnT4(Slc30a4), gene expression in a mammary gland disorder leading to reduced zinc secretion into milk. Hum Genet 2003;113:202-10. [PubMed]

8. Chowanadisai W, Lonnerdal B, Kellher SL. J Biol Chem 2006;281:39699-707. [PubMed]

9. Sehgal VN, Jain S. Acrodermatitis enteropathica. Clin Dermatol 2000; 18: 745-8. [PubMed]

10. Arlette JP. Zinc and the skin. Pediatr Clin North Am 1983; 30:583-96 [PubMed]

11. Chue CD, Rajpar SF, Bhat J.An acrodermatitis enteropathica-like eruption secondary to acquired zinc deficiency in an exclusively breast-fed premature infant. Int J Dermatol 2008;47:372-3. [PubMed]

© 2010 Dermatology Online Journal