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CASE REPORT
Year : 2016  |  Volume : 17  |  Issue : 1  |  Page : 35-37

Clinical variants of acrodermatitis enteropathica and its co-relation with genetics


Department of Dermatology, Venereology and Leprology, Pt. BD Sharma PGIMS, Rohtak, Haryana, India

Date of Web Publication4-Jan-2016

Correspondence Address:
Sarabjit Kaur
House No. 401, Sector 14, Rohtak - 124 001, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2319-7250.173153

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  Abstract 

Acrodermatitis enteropathica (AE) is a rare disorder of zinc deficiency, which manifests as acral and periorificial dermatitis, alopecia, intractable diarrhea, and failure to thrive. It is classified as primary zinc deficiency, genetically based deficiency, and acquired secondary deficiency. We hereby report a case series of genetically based AE in two nonidentical twins of age two months and two siblings of age 3 and 6 months. After reviewing the literature, we have also emphasized the possible role of genetics in the manifestation of AE.

Keywords: Acrodermatits enteropathica, chronic diarrhea, zinc deficiency, zinc transporters


How to cite this article:
Kaur S, Sangwan A, Sahu P, Dayal S, Jain VK. Clinical variants of acrodermatitis enteropathica and its co-relation with genetics. Indian J Paediatr Dermatol 2016;17:35-7

How to cite this URL:
Kaur S, Sangwan A, Sahu P, Dayal S, Jain VK. Clinical variants of acrodermatitis enteropathica and its co-relation with genetics. Indian J Paediatr Dermatol [serial online] 2016 [cited 2020 Jul 12];17:35-7. Available from: http://www.ijpd.in/text.asp?2016/17/1/35/173153


  Introduction Top


Acrodermatitis enteropathica (AE) is caused by zinc deficiency.[1] It can be classified as primary zinc deficiency, genetically based zinc deficiency (classical AE, acquired zinc deficiency of lactogenic origin), and acquired secondary zinc deficiency.[2] The genetic zinc deficiency is associated with the defects in two zinc transporters, one is involved in intestinal zinc uptake Zrt- and Irt-like protein-4 (ZIP), causing classical AE and the other is responsible for zinc secretion in breast milk zinc transporter-2 (ZnT) resulting in zinc deficiency of lactogenic origin.[3] Here, we have discussed and reviewed the clinical aspects and probable role of zinc transporters in the manifestation of AE.


  Case Reports Top


Case 1

Two nonidentical twins of age two months presented in the Department of Dermatology with multiple well defined, erythematous oozy and crusted plaques over the perioral, perinasal area, and scrotum [Figure 1]. History of incessant crying with chronic diarrhea was also elicited. Both babies were exclusively breastfed. History of first-degree consanguinity was present in the parents.
Figure 1: Erythematous scaly plaques over scrotum in both twins and perioral and perinasal crusting in one of the twins

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Estimation of serum zinc levels were found to be significantly decreased in both the twins; 28 μg/dl and 20 μg/dl, respectively, (normal: 70–110 μg/dl). However, the zinc levels in maternal serum and breast milk were normal. Both patients were started on oral zinc therapy (i.e. syrup zinc sulfate) at a dose of 5 mg/kg/day. The lesions improved significantly within three weeks of initiation of treatment. Thus, a diagnosis of classical AE was made on the basis of clinical presentation, low serum zinc levels, and dramatic improvement in lesions after oral zinc therapy. Both the twins were maintained on zinc supplementation at the dose of 2 mg/kg/day and advised lifelong continuation of therapy.

Case 2

A 3-month-old exclusively breastfed male baby, reported to Department of Dermatology with multiple erythematous, moist plaques distributed symmetrically over the perioral, perineal, and buttocks [Figure 2]. History of excessive irritability and chronic diarrhea was present. The parents had no history of consanguinity. Mother revealed similar cutaneous manifestations and chronic diarrhea in her first child, who succumbed to recurrent infections at the age of 6 months. A similar history of cutaneous manifestations and chronic diarrhea was also reported in all three children of her elder sister.
Figure 2: Perioral crusting and erythematous moist scaly plaques over the buttocks in a 3-month-old infant

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The serum zinc level of baby was extremely low (10 μg/dl) while the mother had normal serum zinc level, but markedly decreased zinc level in breast milk (17 μg/dl; normal range, 60–90 μg/dl). Hence, the infant was diagnosed as a case of lactogenic acrodermatitis for which oral zinc supplementation (i.e. syrup zinc sulfate) at a dose of 5 mg/kg/day was initiated. Zinc supplementation was continued till baby was being breastfed and discontinued on weaning.*Serum albumin and serum alkaline phosphatase were within the normal range in both cases.


  Discussion Top


Zinc is an essential element in humans and plays an important role in growth and development.[4]

Clinically, AE is characterized by acral and periorificial dermatitis, alopecia, and diarrhoea, although this classical triad of symptoms occurs in only 20% of cases.[5] It is estimated to affect about one in 500,000 children.[4] Zinc deficiency in infants can be divided into three main subtypes:[2]

  • Primary zinc deficiency due to dietary inadequacy (older breastfed infants or toddlers without zinc-rich complementary foods)
  • Acquired secondary deficiency in low birth weight and premature babies and various malabsorption syndromes
  • Genetically based deficiency (includes classical AE and acquired zinc deficiency of lactogenic origin). The classical AE is caused by a genetically determined defect in intestinal zinc transporters while, the acquired zinc deficiency of lactogenic origin is caused by defective zinc transporter in mother's milk [Flow Chart 1].



ZIP4 is a low molecular weight pancreatic ligand, encoded by SLC39A4 gene (located on chromosomal region 8q24.3) which aids in zinc absorption in the intestine.[6] Alteration in the production of ZIP4 transporter is the basic genetic defect in classical AE thus causing a partial block in intestinal zinc absorption. Classical AE is an autosomal recessive disorder and requires higher serum zinc level so as to overcome this partial block.[2],[3] Diagnosis of classic AE was made in our first case on the basis of decreased serum zinc levels in twins, normal zinc level in breast milk and history of consanguinity in the parents. Initial signs and symptoms appear in early infancy in exclusively breastfed full term infants, as seen in our first case (twins), hence favors our diagnosis.

ZnT2, the transporter present in maternal mammary glands is responsible for zinc secretion in human milk.[3] AE like disease due to a defect in ZnT2, also known as zinc deficiency of lactogenic origin, is characterized by early onset, with a brief and self-limiting course.[7] It clears when the children start their normal solid diet. The diagnosis can be confirmed by a low zinc level in maternal milk, as demonstrated in our second case. Here, the mother's milk is also known as “lethal milk”[7] as it induces hypozincemia and the cow's milk may play a protective role. This variant of AE is also known as transient neonatal zinc deficiency [3] for the purpose of differentiation from classical AE. It has an autosomal dominant inheritance pattern,[3] as evidence of the history of similar illness in all the offspring's of both the sisters (mother and her sister) in our second case.

AE is associated with growth failure, protein energy malnutrition, and increased susceptibility to infections due to impaired cellular and humoral response.[8],[9] It can get complicated with secondary infections such as candidiasis, Gram-positive and Gram-negative bacteria, leading to death,[5] as seen in the elder sister of our second case.

Most authors recommend an initial zinc supplementation at the dose of 5–10 mg/kg/day and maintenance with 1–2 mg/kg/day.[5] High serum levels of zinc lead to hypocupremia, resulting in alteration of immune system thus, necessitating the monitoring of copper levels in patients with classical AE.[4]

To conclude, the literature has mentioned the role of transporter defects in the pathology of AE. Hence, the recognition of genetic zinc deficiency is important because modality of their treatment remains different in both genetic defects. Therefore, the clinical tests for genetic disorders of zinc metabolism need to be developed.

Declaration of Patient Consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial Support and Sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest.

 
  References Top

1.
Moynahan EJ, Barnes PM. Zinc deficiency and a synthetic diet for lactose intolerance. Lancet 1973;1:676-7.  Back to cited text no. 1
[PUBMED]    
2.
Krebs NF. Update on zinc deficiency and excess in clinical pediatric practice. Ann Nutr Metab 2013;62 Suppl 1:19-29.  Back to cited text no. 2
    
3.
Kasana S, Din J, Maret W. Genetic causes and gene–nutrient interactions in mammalian zinc deficiencies: Acrodermatitis enteropathica and transient neonatal zinc deficiency as examples. J Trace Elem Med Biol 2015;29:47-62.  Back to cited text no. 3
[PUBMED]    
4.
Maverakis E, Fung MA, Lynch PJ, Draznin M, Michael DJ, Ruben B, et al. Acrodermatitis enteropathica and an overview of zinc metabolism. J Am Acad Dermatol 2007;56:116-24.  Back to cited text no. 4
    
5.
Perafán-Riveros C, França LF, Alves AC, Sanches JA Jr. Acrodermatitis enteropathica: Case report and review of the literature. Pediatr Dermatol 2002;19:426-31.  Back to cited text no. 5
    
6.
Nakano A, Nakano H, Nomura K, Toyomaki Y, Hanada K. Novel SLC39A4 mutations in acrodermatitis enteropathica. J Invest Dermatol 2003;120:963-6.  Back to cited text no. 6
    
7.
Sharma NL, Sharma RC, Gupta KR, Sharma RP. Self-limiting acrodermatitis enteropathica. A follow-up study of three interrelated families. Int J Dermatol 1988;27:485-6.  Back to cited text no. 7
    
8.
Chandra RK. Acrodermatitis enteropathica: Zinc levels and cell-mediated immunity. Pediatrics 1980;66:789-91.  Back to cited text no. 8
[PUBMED]    
9.
Fraker PJ, Jardieu P, Cook J. Zinc deficiency and immune function. Arch Dermatol 1987;123:1699-701.  Back to cited text no. 9
    


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