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Acrodermatitis enteropathica is an autosomal recessive^[1] metabolic disorder affecting the uptake of zinc, characterized by periorificial (around the natural orifices) and acral (in the limbs) dermatitis, alopecia (loss of hair), and diarrhea.

Similar features may be present in acquired zinc deficiency. This disease also is related to deficiency of zinc due to congenital causes.

Other names for acrodermatitis enteropathica include:

Brandt syndrome
Danbolt-Cross syndrome
Congenital zinc deficiency

Signs and symptoms

Features of acrodermatitis enteropathica start appearing in the first few months of life, as the infant discontinues breast milk. There are erythematous patches and plaques of dry, scaly skin. The lesions may appear eczematous, or may evolve further into crusted vesicles, bullas or pustules. The lesions are frequent around the mouth and anus, and also in hands, feet and scalp. There may be suppurative inflammation of the nail fold surrounding the nail plate - known as paronychia. Alopecia - loss of hair from scalp, eyebrows and eyelashes may occur. The skin lesions may be secondarily infected by bacteria such as Staphylococcus aureus or fungi like Candida albicans. These skin lesions are accompanied by diarrhea.

Genetics

Acrodermatitis enteropathica has an autosomal recessive pattern of inheritance.

A mutation of the SLC39A4 gene on chromosome 8 q24.3 is responsible for the disorder.^[2] The SLC39A4 gene encodes a transmembrane protein that serves as a zinc uptake protein. The features of the disease usually start manifesting as an infant is weaned from breast milk. This has led some scientists to suspect that human milk contains a beneficial substance that helps uptake of zinc and prevents the disease from being manifested while an infant is on breast milk.^[3]

Treatment

Without treatment, the disease is fatal and affected individuals may die within a few years. There is no cure for the condition. Treatment includes lifelong dietary zinc supplementation in the range of greater than 1–2 mg/kg of bodyweight per day.

References

^ Wang, K; Pugh, Ew; Griffen, S; Doheny, Kf; Mostafa, Wz; Al-Aboosi, Mm; El-Shanti, H; Gitschier, J (April 2001). "Homozygosity mapping places the acrodermatitis enteropathica gene on chromosomal region 8q24.3". American Journal of Human Genetics 68 (4): 1055–60. doi:10.1086/319514. PMC 1275625. PMID 11254458.
^ Küry, S; Dréno, B; Bézieau, S; Giraudet, S; Kharfi, M; Kamoun, R; Moisan, Jp (July 2002). "Identification of SLC39A4, a gene involved in acrodermatitis enteropathica". Nature Genetics 31 (3): 239–40. doi:10.1038/ng913. PMID 12068297.
^ Michalczyk, A; Varigos, G; Catto-Smith, A; Blomeley, Rc; Ackland, Ml (August 2003). "Analysis of zinc transporter, hZnT4 ( Slc30A4), gene expression in a mammary gland disorder leading to reduced zinc secretion into milk". Human Genetics 113 (3): 202–10. doi:10.1007/s00439-003-0952-2. PMID 12743795.

External links

OMIM entry on ACRODERMATITIS ENTEROPATHICA, ZINC-DEFICIENCY TYPE; AEZ
DermNet systemic/acrodermatitis-enteropathica
WebMD article
Doctor's doctor article
Dermis.net article with images
Google Group - Acrodermatitis Enteropathica Circle

UpToDate Contents

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1. 小児および思春期における亜鉛の欠乏および補充 zinc deficiency and supplementation in children and adolescents
2. ジアノッティ・クロスティ症候群（丘疹性末端皮膚炎） gianotti crosti syndrome papular acrodermatitis
3. 食物中の微量ミネラルの概要 overview of dietary trace minerals
4. Pathogenesis, clinical manifestations, and diagnosis of atopic dermatitis (eczema)
5. Diaper dermatitis

English Journal

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

Lova Navarro M1, Vera Casaño A, Benito López C, Fernández Ballesteros MD, Godoy Díaz DJ, Crespo Erchiga A, Romero Brufau S.Author information 1Department of Dermatology, Hospital Materno-Infantil, Complejo Hospitalario Carlos Haya, Málaga, Spain.AbstractTransient 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.
Pediatric dermatology.Pediatr Dermatol.2014 Mar;31(2):251-2. doi: 10.1111/pde.12257. Epub 2014 Jan 23.
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 complementa
PMID 24456035

Extreme population differences in the human zinc transporter ZIP4 (SLC39A4) are explained by positive selection in Sub-Saharan Africa.

Engelken J1, Carnero-Montoro E2, Pybus M2, Andrews GK3, Lalueza-Fox C2, Comas D2, Sekler I4, de la Rasilla M5, Rosas A6, Stoneking M7, Valverde MA8, Vicente R8, Bosch E2.Author information 1Institute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain ; Department of Evolutionary Genetics, Max-Planck Institute for Evolutionary Anthropology, Leipzig, Germany.2Institute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.3Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas, United States of America.4Department of Physiology, Ben-Gurion University, Beer-Sheva, Israel.5Área de Prehistoria, Departamento de Historia, Universidad de Oviedo, Oviedo, Spain.6Group of Paleoanthropology MNCN-CSIC, Department of Paleobiology, National Museum of Natural Sciences, CSIC, Madrid, Spain.7Department of Evolutionary Genetics, Max-Planck Institute for Evolutionary Anthropology, Leipzig, Germany.8Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.AbstractExtreme differences in allele frequency between West Africans and Eurasians were observed for a leucine-to-valine substitution (Leu372Val) in the human intestinal zinc uptake transporter, ZIP4, yet no further evidence was found for a selective sweep around the ZIP4 gene (SLC39A4). By interrogating allele frequencies in more than 100 diverse human populations and resequencing Neanderthal DNA, we confirmed the ancestral state of this locus and found a strong geographical gradient for the derived allele (Val372), with near fixation in West Africa. In extensive coalescent simulations, we show that the extreme differences in allele frequency, yet absence of a classical sweep signature, can be explained by the effect of a local recombination hotspot, together with directional selection favoring the Val372 allele in Sub-Saharan Africans. The possible functional effect of the Leu372Val substitution, together with two pathological mutations at the same codon (Leu372Pro and Leu372Arg) that cause acrodermatitis enteropathica (a disease phenotype characterized by extreme zinc deficiency), was investigated by transient overexpression of human ZIP4 protein in HeLa cells. Both acrodermatitis mutations cause absence of the ZIP4 transporter cell surface expression and nearly absent zinc uptake, while the Val372 variant displayed significantly reduced surface protein expression, reduced basal levels of intracellular zinc, and reduced zinc uptake in comparison with the Leu372 variant. We speculate that reduced zinc uptake by the ZIP4-derived Val372 isoform may act by starving certain pathogens of zinc, and hence may have been advantageous in Sub-Saharan Africa. Moreover, these functional results may indicate differences in zinc homeostasis among modern human populations with possible relevance for disease risk.
PLoS genetics.PLoS Genet.2014 Feb 20;10(2):e1004128. doi: 10.1371/journal.pgen.1004128. eCollection 2014.
Extreme differences in allele frequency between West Africans and Eurasians were observed for a leucine-to-valine substitution (Leu372Val) in the human intestinal zinc uptake transporter, ZIP4, yet no further evidence was found for a selective sweep around the ZIP4 gene (SLC39A4). By interrogating a
PMID 24586184

Maple Syrup Urine Disease Complicated with Kyphoscoliosis and Myelopathy.

Hou JW.Author information Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan. Electronic address: hou76@cgh.org.tw.AbstractMaple syrup urine disease (MSUD) is an autosomal recessive aminoacidopathy secondary to an enzyme defect in the catabolic pathway of the branched-chain amino acids (BCAAs: leucine, isoleucine, and valine). Accumulation of their corresponding keto-acids leads to encephalopathy if not treated in time. A newborn male patient was suspected to have MSUD after tandem mass study when he presented symptoms and signs suggestive neonatal sepsis, anemia, and diarrhea. Food restriction of BCAAs was started; however, acrodermatitis enteropathica-like skin eruptions occurred at age 2 months. The skin rashes resolved after adding BCAAs and adjusting the infant formula. At age 7 months, he suffered from recurrent skin lesions, zinc deficiency, osteoporosis, and kyphosis of the thoracic spine with acute angulation over the T11-T12 level associated with spinal compression and myelopathy. After supplementation of zinc products and pamidronate, skin lesions and osteopenia improved gradually. Direct sequencing of the DBT gene showed a compound heterozygous mutation [4.7 kb deletion and c.650-651insT (L217F or L217fsX223)]. It is unusual that neurodegeneration still developed in this patient despite diet restriction. Additionally, brain and spinal magnetic resonance imaging, bone mineral density study, and monitoring of zinc status are suggested in MSUD patients.
Pediatrics and neonatology.Pediatr Neonatol.2014 Jan 29. pii: S1875-9572(13)00235-0. doi: 10.1016/j.pedneo.2013.10.013. [Epub ahead of print]
Maple syrup urine disease (MSUD) is an autosomal recessive aminoacidopathy secondary to an enzyme defect in the catabolic pathway of the branched-chain amino acids (BCAAs: leucine, isoleucine, and valine). Accumulation of their corresponding keto-acids leads to encephalopathy if not treated in time.
PMID 24486081

Japanese Journal

Overview of Inherited Zinc Deficiency in Infants and Children (Nutrition and Food for Longevity : For the Well-Being of All : Proceedings of the 12th Asian Congress of Nutrition)

KAMBE Taiho,FUKUE Kazuhisa,ISHIDA Riko [他]
Journal of nutritional science and vitaminology 61(Suppl.), S44-46, 2015-05
NAID 40020444113

亜鉛栄養と亜鉛トランスポーター(<特集>第66回大会シンポジウム「ビタミン・バイオファクタートランスポーター研究の最前線」)

神戸大朋
ビタミン 88(11), 560-564, 2014-11-25
Zinc is an essential trace element that plays a pivotal role as a structural, catalytic, and signaling component within protein functions. Adequate intake of zinc from daily diets is indispensable for …
NAID 110009894952