Laboratory Studies

Plasma zinc levels are low in patients with acrodermatitis enteropathica (AE), and characteristic histopathologic findings are seen on skin biopsy.

Hair, urine, and parotid saliva zinc levels, as well as serum alkaline phosphatase activity (which lowers later in the disease) may be helpful.

Maternal breast milk zinc concentrations also may help differentiate AE from acquired zinc deficiency.

Other Tests

The gene for AE is localized to chromosomal region 8q24.3 and the SLC39A4 gene, thereby identified as the gene for AE. SLC39A4 mutations have been demonstrated in several families with AE, and, in the initial Nakano study, two Japanese families with AE and with SLC39A4 mutations were described.^[15]Their mutation detection strategy consisted of polymerase chain reaction amplification of all 12 exons and flanking of intronic sequences, followed by direct nucleotide sequencing. It revealed 3 novel mutations, 1017ins53, which creates a premature termination codon, and 2 mis-sense mutations, R95C and Q303H. These techniques can be used to identify carriers, newborns, or fetuses by amniocentesis.

Histologic Findings

Histopathologic examination of the skin and eyelids reveals parakeratosis of the stratum corneum with occasional neutrophils and intracellular edema. The granular cell layer is diminished, and the upper epidermis demonstrates pallor and edema. Focal dyskeratosis is seen. The epidermis may be psoriasiform or atrophic. Occasionally, subcorneal (cutaneous) pustules are seen.

One case report details the ocular histopathology of a child who died before efficacious treatment was available. The findings include corneal epithelial thinning and loss of polarity of corneal epithelial cells, anterior corneal scarring and loss of Bowman membrane, cataract formation, ciliary body atrophy, retinal degeneration, retinal pigment epithelium (RPE) depigmentation, and optic atrophy.

Treatment & Management

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Andrews GK. Regulation and function of Zip4, the acrodermatitis enteropathica gene. Biochem Soc Trans. 2008 Dec. 36:1242-6. [QxMD MEDLINE Link].
Kambe T, Andrews GK. Novel proteolytic processing of the ectodomain of the zinc transporter ZIP4 (SLC39A4) during zinc deficiency is inhibited by acrodermatitis enteropathica mutations. Mol Cell Biol. 2009 Jan. 29(1):129-39. [QxMD MEDLINE Link].
Coromilas A, Brandling-Bennett HA, Morel KD, Chung WK. Novel SLC39A4 mutation in acrodermatitis enteropathica. Pediatr Dermatol. 2011 Nov-Dec. 28(6):697-700. [QxMD MEDLINE Link].
Wessells KR, King JC, Brown KH. Development of a plasma zinc concentration cutoff to identify individuals with severe zinc deficiency based on results from adults undergoing experimental severe dietary zinc restriction and individuals with acrodermatitis enteropathica. J Nutr. 2014 Aug. 144(8):1204-10. [QxMD MEDLINE Link].
Mirza GE, Sevim DG. Ocular symptoms as the initial signs of zinc deficiency. J AAPOS. 2016 Feb. 20 (1):77-8. [QxMD MEDLINE Link].
Ciampo IRLD, Sawamura R, Ciampo LAD, Fernandes MIM. ACRODERMATITIS ENTEROPATHICA: CLINICAL MANIFESTATIONS AND PEDIATRIC DIAGNOSIS. Rev Paul Pediatr. 2018 Apr-Jun. 36 (2):238-241. [QxMD MEDLINE Link].
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Evans GW, Johnson PE. Characterization and quantitation of a zinc-binding ligand in human milk. Pediatr Res. 1980 Jul. 14(7):876-80. [QxMD MEDLINE Link].
Lonnerdal B, Stanislowski AG, Hurley LS. Isolation of a low molecular weight zinc binding ligand from human milk. J Inorg Biochem. 1980 Jan. 12(1):71-8. [QxMD MEDLINE Link].
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Bin BH, Bhin J, Kim NH, Lee SH, Jung HS, Seo J, et al. An Acrodermatitis Enteropathica-Associated Zn Transporter, ZIP4, Regulates Human Epidermal Homeostasis. J Invest Dermatol. 2017 Apr. 137 (4):874-883. [QxMD MEDLINE Link].
Nakano A, Nakano H, Nomura K. Novel SLC39A4 mutations in acrodermatitis enteropathica. J Invest Dermatol. 2003. Jun;120(6):963-6. [QxMD MEDLINE Link]. [Full Text].
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Media Gallery

Sharply demarcated, brightly erythematous periorificial plaque in an infant with acrodermatitis enteropathica.

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Author

John D Sheppard, Jr, MD, MMSc Professor of Ophthalmology, Microbiology and Molecular Biology, Clinical Director, Thomas R Lee Center for Ocular Pharmacology, Ophthalmology Residency Research Program Director, Eastern Virginia Medical School; President, Virginia Eye Consultants

John D Sheppard, Jr, MD, MMSc is a member of the following medical societies: American Academy of Ophthalmology, American Society for Microbiology, American Society of Cataract and Refractive Surgery, American Uveitis Society, Association for Research in Vision and Ophthalmology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: 1-800-DOCTORS; AbbVie; Alcon; Aldeyra; Allergan; Alphaeon; ArcScan; Baush+Lomb; Bio-Tissue; Clearside; EyeGate; Hovione; Mededicus; NovaBay; Omeros; Pentavision; Portage; Santen; Science Based Health; Senju; Shire; Sun Pharma; TearLab;TearScience;Topivert Serve(d) as a speaker or a member of a speakers bureau for: AbbVie; Alcon; Allergan; Bausch+Lomb; Bio-tissue; EyeGate;Hovione;LayerBio; NovaBay;Omeros;Portage; Santen; Shire; Stemnion; Sun Pharma;TearLab;TearScience; Topivert Received research grant from: Alcon; Aldeyra; allergan; Baush+ Lomb; EyeGate; Hovione; Kala; Ocular Therapeutix;Pfizer; RPS; Santen;Senju;Shire;Topcon; Xoma.

Coauthor(s)

Isabelle Dortonne, MD Resident Physician, Department of Ophthalmology, Eastern Virginia Medical School

Disclosure: Nothing to disclose.

Specialty Editor Board

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Glaucoma Society

Disclosure: Nothing to disclose.

Christopher J Rapuano, MD Professor, Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University; Director of the Cornea Service, Wills Eye Hospital

Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Ophthalmological Society, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Cornea Society, Eye Bank Association of America, International Society of Refractive Surgery

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: AAO; OMIC; American Society of Ophthalmic Trauma (ASOT); Avellino, Baxis; Bio-Tissue; Celularity; Dompe; Emmecell; Glaukos; Kala; Oyster Point; Sun Ophthalmics; Tarsus; TearLab Serve(d) as a speaker or a member of a speakers bureau for: Glaukos; Dompe; Bio-Tissue Received research grant from: Glaukos Received income in an amount equal to or greater than $250 from: AAO; OMIC; Baxis; Bio-Tissue; Cellularity; Dompe; Glaukos; Kala; Sun Ophthalmics; TearLab stock options for: RPS, Fount Bio.

Chief Editor

Hampton Roy, Sr, MD † Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

Andrew A Dahl, MD, FACS Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center

Andrew A Dahl, MD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Intraocular Lens Society, American Medical Association, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Medical Society of the State of New York, New York State Ophthalmological Society, Outpatient Ophthalmic Surgery Society

Disclosure: Nothing to disclose.

Timothy G Woodall, MD Dermatology, Carolinas Medical Center - Pineville

Timothy G Woodall, MD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, South Carolina Medical Association

Disclosure: Nothing to disclose.