One novel homozygous mutation of SLC39A4 gene in a Chinese patient with acrodermatitis enteropathica

Acrodermatitis enteropathica, a rare autosomal recessive disease, manifests as periorificial and symmetrical acral dermatitis, alopecia, and diarrhea due to insufficient zinc uptake by the intestine. Recent research revealed that mutations in the SLC39A4 gene are responsible for acrodermatitis enteropathica. This gene encodes one member of a human zinc transporter-like protein, also known as ZIP4. We detected one novel homozygous mutation c.1115T > G in the human SLC39A4 gene in one Chinese patient, which leading to p.L372R of the ZIP4. Homology analysis shows Leu372 in ZIP4 is conserved in Eutheria.     

Acrodermatitis Enteropathica: A Novel SLC39A4 Gene Mutation in a Patient with Normal Zinc Levels

Acrodermatitis enteropathica (AE) is a rare disease that results from a defective gene, SLC39A4, and is characterized by dermatitis, alopecia, and diarrhea. We report a case of AE presenting with only periorificial and acral dermatitis in which genetic testing revealed two novel compound heterozygous missense mutations for SLC39A4. This case demonstrates that not all AE mutations alter zinc transporters in the same manner and highlights the phenotypic variability of AE.     

Acrodermatitis enteropathica

A 13-year-old girl presented with a history of red scaly plaques involving the chest, arms and legs beginning in infancy. Punch biopsy revealed psoriasiform hyperplasia and pallor of the epidermis. The patient's serum zinc level was 36 mug/dl [nl. 66-144 mug/dl]. A diagnosis of acrodermatitis enteropathica was established and the patient responded well to zinc replacement therapy. Acrodermatitis enteropathica is a rare autosomal recessive disorder caused by mutations in SLC39A4, which encodes the tissue-specific zinc transporter ZIP4.     

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.     

Novel SLC39A4 mutations in acrodermatitis enteropathica

Acrodermatitis enteropathica is an autosomal recessive disease characterized by skin involvement due to defective intestinal zinc absorption. Usually, the skin lesions include erythema, erosions, and small blisters in perioral, perianal regions, and hands and feet, which develop soon after weaning from the breast. The acrodermatitis enteropathica gene has been localized to chromosomal region 8q24.3 and subsequently the SLC39A4 gene has been disclosed as the acrodermatitis enteropathica gene. SLC39A4 mutations have been demonstrated in several acrodermatitis enteropathica families, and in this study we have examined two Japanese acrodermatitis enteropathica families for SLC39A4 mutations. The mutation detection strategy consisted of polymerase chain reaction amplification of all 12 exons and flanking intronic sequences, followed by direct nucleotide sequencing. It revealed three novel mutations, 1017ins53, which creates a premature termination codon, and two mis-sense mutations, R95C and Q303H.     

Novel SLC39A4 mutation in acrodermatitis enteropathica

Acrodermatitis enteropathica (AE) is a rare autosomal-recessive disorder characterized by dermatitis, alopecia, diarrhea, and retardation of growth and development. AE maps to 8q24.3 and is associated with mutations in the intestinal zinc transporter ZIP4 encoded by the gene SLC39A4. We describe a novel homozygous mutation, 1191insC, in SLC39A4 in a patient from Sierra Leone and suggest that AE should be considered within the differential diagnosis for acrodermatitis in children from Sierra Leone. Genetic testing for this founder mutation can be easily performed for this treatable disorder.     

Acquired Zinc Deficiency in an Adult Female

Acrodermatitis enteropathica is an autosomal recessive inherited disorder of zinc absorption. Acquired cases are reported occasionally in patients with eating disorders or Crohn''s disease. We report a 24-year-old housewife with acquired isolated severe zinc deficiency with no other comorbidities to highlight the rare occurrence of isolated nutritional zinc deficiency in an otherwise normal patient.     

A case of acrodermatitis enteropathica

Acrodermatitis enteropathica is a rare hereditary disorder affecting zinc metabolism that is characterized by dermatitis, alopecia, gastrointestinal disturbances, eye infections, and growth failure. We report a 17-month-old girl with acrodermatitis enteropathica. Physical examination showed a cutaneous eruption consisting of vesiculobullous and psoriasiform skin lesions symmetrically distributed in the perioral, acral, and perineal areas. Her plasma zinc level was decreased (75 micrograms/dl), but within the normal range (60.00-135.00 micrograms/dl). The patient was given zinc sulfate 50 mg/day. At the end of two months, she had significantly improved.     

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.     

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.     

Acrodermatitis enteropathica-like skin eruption in a case of short bowel syndrome following jejuno-transverse colon anastomosis

Acrodermatitis enteropathica is a rare autosomal recessive disorder of zinc deficiency. Zinc is an essential trace element in human metabolism and acquired zinc deficiency may manifest with skin eruptions simulating acrodermatitis enteropathica. We report an unusual case of acrodermatitis enteropathica-like skin eruption due to deficiency of zinc and other nutritional factors in a patient who has undergone extensive small bowel resection and jejuno-transverse colon anastomosis for mesenteric ischemia.     

Acrodermatitis enteropathica

A case of acrodermatitis enteropathica belatedly recognized in a pregnant 23-year-old woman is reported. The condition was not specifically diagnosed during childhood. It cleared at puberty but recurred during two of three pregnancies in the form of pustular, vesiculobullous, and psoriasiform lesions. There were no associated signs or symptoms in other organs. Initial diagnoses upon the recurrence during the third pregnancy were herpes gestationis and impetigo herpetiformis. A markedly decreased serum zinc level (18 micrograms/dl) was found. Treatment with zinc sulfate was instituted, and within 3 days the cutaneous lesions began to clear. Two months after the birth of a healthy child, and without further therapy, all lesions had resolved and the serum zinc level was nearly normal. Acrodermatitis enteropathica should be considered in the differential diagnosis of unresponsive bullous dermatoses occurring during pregnancy.     

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.     

Acrodermatitis enteropathica-like eruption in an infant with nonketotic hyperglycinemia

Acrodermatitis enteropathica is a rare inherited disorder characterized by zinc deficiency and a triad of dermatitis, diarrhea, and alopecia. It is an autosomal recessive condition thought to be due to the inability to absorb zinc from the gastrointestinal tract. Acquired zinc deficiency due to a variety of etiologies may produce a similar clinical picture. These causes include inadequate supply, malabsorption, and low zinc stores. In addition to zinc, deficiencies of other nutrients such as branched chain amino acids have induced an acrodermatitis enteropathica-like eruption. We describe a case of a 26-month-old boy with a rare inborn error of metabolism known as nonketotic hyperglycinemia who developed an acrodermatitis enteropathica-like eruption. In addition to zinc deficiency, the patient was deficient in branched chain amino acids due to a low protein diet instituted to reduce his elevated glycine levels. The rash did not respond to zinc replacement alone, and therefore is most likely a combination of amino acid and zinc deficiency. Acrodermatitis enteropathica-like eruptions have been described in other conditions that cause decreased serum amino acids, such as maple syrup urine disease and organic acidurias. This is the first case describing an association between acrodermatitis enteropathica and nonketotic hyperglycinemia.     

Zinc deficiency: report of three cases

Acrodermatitis enteropathica has been reported as the skin disorder due to the congenital disturbance of zinc absorption in the intestine. We report on three patients with skin eruptions that resembled acrodermatitis enteropathica. Two were thought to have resulted from intravenous hyperalimentation and the other from artificial feeding.     

Genomic localization, organization and amplification of the human zinc transporter protein gene, ZNT4, and exclusion as a candidate gene in different clinical variants of acrodermatitis enteropathica

Abstract Acrodermatitis enteropathica is an inherited disorder of zinc metabolism, the molecular basis of which is currently unknown. Recent transgenic mouse studies have highlighted the potential significance of certain zinc transport proteins, for example ZnT4, in providing clues to the pathogenesis of zinc-related disorders such as acrodermatitis enteropathica. Specifically, mice of any genotype suckled on ZnT4-deficient mice fail to absorb intestinal zinc and ZnT4-deficient mice also develop dermatitis, alopecia and stunted growth. Therefore, to assess human ZnT4 as a candidate gene/protein in acrodermatitis enteropathica or related disorders, we characterized the intron-exon organization of the human ZNT4 gene, which comprises seven distinct exons spanning approximately 38.7 kb. High-resolution radiation hybrid mapping placed ZNT4 on 15q21.1. We also developed a PCR-based mutation detection strategy using primers placed on flanking introns followed by direct sequencing of the PCR products. Using this approach, we sequenced DNA from five individuals with acrodermatitis enteropathica; no mutations were identified. Thus, ZNT4 is unlikely to be the correct candidate gene for this disorder. We also identified and characterized two common single nucleotide polymorphisms in exon 5 and in the 3′ UTR of ZNT4, which will be useful for future genetic linkage studies in assessing ZNT4 as a candidate gene for other inherited disorders of zinc metabolism. Received: 27 December 2000 / Revised: 12 May 2001 / Accepted: 2 June 2001     

AN ACQUIRED FORM OF ACRODERMATITIS ENTEROPATHICA DUE TO LONGTERM LACTOSE-FREE MILK ALIMENTATION

A 4-month-old boy, fed on lactose-free milk for the treatment of intractable diarrhea for about 3 months, developed acrodermatitis enteropathica-like skin lesions. All the symptoms dramatically disappeared 2 weeks after switching from this milk to a general cow's milk formula, and his low serum zinc level also rapidly returned to normal. The zinc deficiency seen in this case was presumed to be closely related to longterm lactose-free milk alimentation. Acrodermatitis enteropathica, a human zinc deficiency, should be classified into two types, hereditary and acquired. The latter form can develop from intravenous hyperalimentation, longterm lactose-free milk alimentation and longterm penicillamine administration.     

Acrodermatitis enteropathica: case report and review of the literature

Acrodermatitis enteropathica (AE) is a rare hereditary disorder caused by impaired absorption of zinc from the gastrointestinal tract. It is characterized by acral and periorificial dermatitis, alopecia, and diarrhea. Symptoms usually begin on weaning from breast or formula feeding. We report a full-term, 21-month-old boy with typical skin lesions and decreased plasma zinc level (12 micro g/dl). The patient was given zinc sulfate 40 mg/day and at the end of 1 month his condition had improved significantly. After reviewing the literature we emphasize the important role of zinc in human metabolism and the difference between AE and acquired zinc deficiencies.     

A novel homozygous mutation p.E88K in maternal SLC30A2 gene as a cause of transient neonatal zinc deficiency

The SLC30A2 gene encodes zinc transporter ZnT2, which is indispensable for the transport of zinc into the breast milk in the mammary gland. Transient neonatal zinc deficiency (TNZD) is caused by a mutation in the maternal SLC30A2 gene and has a clinical presentation similar to that of acrodermatitis enteropathica (AE). We described the case of a Chinese infant who presented with AE-like lesions 10 days after birth. Sanger sequencing of the AE-causing gene SLC39A4 revealed no mutations in genomic DNA from the infant, excluding the possibility of AE. Detection of the mother's breast milk showed a significantly lower zinc level. Thus, SLC30A2 sequencing was performed on her genomic DNA and a previously unreported homozygous c.262G > A (p.E88K) mutation was disclosed. Functional analysis suggested the novel mutation could lead to a strong disruption of zinc secretion, which indicated a complete loss of function in the ZnT2 protein. We finally diagnosed the infant with TNZD. To the best of our knowledge, this is the first case of TNZD caused by a homozygous mutation in the maternal SLC30A2 gene. Compared to the heterozygous condition, a homozygous mutation seems to result in a more significant decrease in zinc secretion and a more rapid onset of TNZD.