肠病性肢端皮炎研究进展

肠病性肢端皮炎(acrodermatitis enteropathica,AE)是一种锌缺乏性疾病,本病临床特征为腔口周围及肢端皮炎、秃发和腹泻三联征。临床上AE可由基因突变导致肠道锌吸收障碍引起,称为遗传性AE或典型性AE,也可由各种获得性因素导致锌缺乏所致,后者称为获得性AE或获得性AE样疾病,二者在发病机制、治疗及预后上显著不同。目前发现SLC39A4基因是遗传性AE的致病基因,故SLC39A4基因突变检测可作为区分遗传性AE或获得性AE的重要手段,该文就AE研究的最新进展进行综述。     

血清锌正常的肠病性肢端皮炎患儿1例SLC39A4基因突变检测

目的 报道1例血清锌正常肠病性肢端皮炎患儿及SLC39A4基因新突变位点。方法 收集患儿及家系成员临床资料及外周血,检测患儿血清锌及碱性磷酸酶水平,并对家系成员进行基因测序。结果 3次检测患儿血清锌水平分别为57.3、48.0和47.7μmol/L,均处于正常范围,但血清碱性磷酸酶(ALP)水平偏低(34 U/L)。基因测序发现,患儿存在SLC39A4基因c.1462＿1474+1delAGACTGAGCCCAGG(p.Arg488fs)和c.296C>T(p.Ala99Val)复合杂合变异。结论 该例血清锌正常的肠病性肢端皮炎患儿,SLC39A4基因中发现新的突变位点：c.296C>T(p.Ala99Val),本研究扩展了肠病性肢端皮炎的基因突变谱。     

暂时性症状性锌缺乏18例临床分析及SLC39A4基因检测

<正>暂时性症状性锌缺乏(transient symptomatic zinc deficiency,TSZD)发生于婴儿,临床表现为肢端及腔口周围皮炎、脱发及腹泻,常伴低锌血症,与肠病性肢端皮炎(acrodermatitis enteropathica,AE)非常相似,极易混淆。SLC39A4基因为AE的致病基因,我们收集了四川地区18例经SLC39A4基因检测证实为TSZD的患儿资料,将其临床特点总结如下。1资料和方法1.1临床资料收集2010年1月—2012年12月四川地区18例汉族TSZD患儿资料,所有患儿均有AE的常见临床     

肠病性肢端皮炎SLC39A4基因突变

目的研究1例散发肠病性肢端皮炎(acrodermatitis enteropathica,AE)患者及其家系的SLC39A4基因突变情况,为完善该病的发病机制和产前咨询提供生物学依据。方法收集AE患者及其家系成员的临床资料和外周血,采用PCR技术对SLC39A4基因编码区及其侧翼进行扩增,并进行DNA测序。结果该患者SLC39A4基因发现c.948delC的纯合核苷酸变异,该变异导致从第317号氨基酸Val开始的氨基酸合成发生改变,并在改变后的第32个氨基酸终止,为移码突变。该患者的父亲和母亲均发现c.948delC杂合突变,其弟弟及与该家系无血缘关系的100例正常对照均未发现此突变。结论 SLC39A4基因c.948delC纯合突变是导致该AE患者发病的机制。此突变之前未有报道,有助于了解AE基因型与表现型的关系。     

肠病性肢端皮炎的研究进展

肠病性肢端皮炎是一种常染色体隐性遗传病,好发于婴幼儿。典型症状为四肢末端及腔口周围对称性皮炎、间歇性腹泻、脱发三联征。目前认为该病是由SLC39A4基因突变影响了肠道锌的吸收,患者血锌水平明显降低,给予补锌治疗后能显著改善临床症状。     

肠病性肢端皮炎的研究进展

肠病性肢端皮炎是一种常染色体隐性遗传病，好发于婴幼儿。典型症状为四肢末端及腔口周围对称性皮炎、间歇性腹泻、脱发三联征。目前认为该病是由SLC39A4基因突变影响了肠道锌的吸收，患者血锌水平明显降低，给予补锌治疗后能显著改善临床症状。     

肠病性肢端皮炎发病机制的研究进展

肠病性肢端皮炎（AE）是一种一临床上多见于婴儿的锌代谢障碍性疾病，一临床表现具有一定特点，AE与获得性锌缺乏导致的AE样疾病有着本质不同；目前AE发病机制的研究已有某些突破性进展，人们对体内转运金属离子的蛋白家族如SLC39家族的一些特性也逐渐开始有所了解。     

肠病性肢端皮炎研究进展

肠病性肢端皮炎(acrodermatitis enteropathica,AE)是一种少见的以缺锌为特点的常染色体隐性遗传病,常在婴幼儿期发病,病情迁延不愈,严重时可致患儿死亡。该病临床上与暂时性症状性锌缺乏(transient symptomatic zinc deficiency,TSZD)极为相似,容易混淆。近年来SLC39A4被确定为AE的致病基因,这为二者的鉴别提供了可靠手段。该文就AE研究的最新进展进行综述。     

获得性婴儿锌缺乏症1例

婴儿锌缺乏症分为遗传性锌缺乏症[即肠病性肢端皮炎(acrodermatitis enteropathica,AE)]与获得性锌缺乏症(acquired zinc deficiency)[也称暂时性症状性锌缺乏(transient symptomatic zinc deficiency,TSZD)],后者发病率较前者高,...     

播散性浅表性光化性汗孔角化症SLC17A9基因突变分析

目的：检测11例山东汉族播散性浅表性光化性汗孔角化症SLC17A9基因突变位点。方法：提取患者外周血DNA,采用PCR扩增患者SLC17A9基因的全部外显子及其侧翼序列,对PCR扩增产物直接测序检测。结果：11例DSAP患者的SLC17A9基因编码区的所有外显子均未发现突变。结论：本研究中11例DSAP患者的发病与SLC17A9基因的编码区序列无关。     

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.     

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.     

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.     

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.     

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.     

Acrodermatitis enteropathica: an uncommon differential diagnosis in childhood – first description of a new sequence variant

An 11‐month‐old boy was brought to our clinic with superinfected, sharply‐defined, symmetrical, erythematous macules and vesicles, some with yellowish‐brownish crusts, on the cheeks, fingers, and in the diaper region. The suspected impetigo contagiosa had failed to respond to both topical antiseptic therapy and systemic antibiotics. Because of the unusual clinical picture and course, we measured the serum zinc level. A significantly reduced level of 2 μmol/l (normal range 9.2–18.4 μmol/l) was identified. Initial skin lesions had appeared one week after weaning (5th week after birth). Since the age of 8 months the infant had also had recurrent diarrhea. Two weeks after zinc‐histidine substitution, the diarrhea ceased and skin lesions slowly disappeared. Molecular genetic testing for the SLC39A4 (zinc transporter) gene revealed compound heterozygosity for the previously unidentified mutations c.1465_1474+4del (p.?) and c.295G>A (p.Ala99Thr). The parents are healthy heterozygous gene carriers. The same compound heterozygosity was later detected in the newborn brother of our patient shortly after birth. A zinc deficiency could therefore be identified and treated before symptoms occurred. The inherited autosomal recessive zinc transporter deficiency is termed acrodermatitis enteropathica. Lifelong zinc substitution is recommended. A differential diagnosis can be difficult because bacterial and fungal superinfection is common in zinc deficiency. Precise diagnosis requires testing family members for the gene.     

Transient Neonatal Zinc Deficiency Caused by a Novel Mutation in the SLC30A2 Gene

This is a case report of a 4‐month‐old full‐term, fully breastfed boy who presented with a persistent periorificial and groin rash associated with poor weight gain and irritability. His serum zinc level was low. The mother's breast milk zinc level was found to be low despite her serum zinc levels being normal, confirming the diagnosis of transient neonatal zinc deficiency. Mutational analysis revealed a novel mutation in the mother's SLC30A2 gene, which encodes a zinc transporter expressed in mammary gland epithelial cells.     

Transient zinc deficiency syndrome in a breast-fed infant due to decreased zinc in breast milk (type II hypozincemia of infancy): A case report and review of the literature

Type II hypozincemia of infancy is a rare, hereditary zinc deficiency occurring in infants while exclusively on breast feeding. It is caused by defective transfer of zinc into breast milk. Only a few dozen cases have been reported. A 6-month-old, full-term, breast-fed female infant presented with a 3-week history of erythematous to dusky red papules and annular plaques over the perioral and diaper area as well as the digits. The eruption was accompanied by poor appetite and irritable crying. Serum zinc was low (4.896 μmol/L, normal = 10.71?18.36 μmol/L) in the patient but was normal in the mother. Interestingly, the zinc level in the breast milk was very low (2.142 μmol/L; normal postpartum zinc = 18.36 μmol/L at 6 months). Histopathology of a skin biopsy specimen showed spongiotic psoriasiform dermatitis with pallor of superficial keratinocytes, consistent with deficiency disease. With oral zinc sulfate supplement, her skin lesions improved significantly within 4 days. Type II hypozincemia needs to be differentiated from the classical hereditary acrodermatitis enteropathica, which typically develops symptoms after weaning because of poor intestinal absorption of zinc in the affected infants. Mutations in zinc transporter genes have been detected in SLC39A4 (Zip4) and SLC30A2 (ZnT2), respectively, in classical acrodermatitis enteropathica and type II hypozincemia. No mutation was found in these two genes in the present pedigree. Therefore, the genetic defect in our patient might involve other zinc transporter genes.     

Acquired acrodermatitis enteropathica due to zinc‐depleted parenteral nutrition

Well‐known causes of zinc deficiency, also referred to as acrodermatitis enteropathica (AE), include defects in intestinal zinc transporters and inadequate intake, but a rare cause of acquired zinc deficiency discussed here is an iatrogenic nutritional deficiency caused by parenteral nutrition administered without trace elements. While zinc‐depleted parenteral nutrition causing dermatosis of acquired zinc deficiency was first reported in the 1990s, it is now again relevant due to a national vitamin and trace element shortage. A high index of suspicion may be necessary to diagnose zinc deficiency, particularly because early clinical findings are nonspecific. We present this case of acquired zinc deficiency in a patient admitted to a pediatric intensive care unit for respiratory distress and atypical pneumonia, who subsequently developed a severe bullous eruption due to iatrogenic zinc deficiency but was treated effectively with enteral and parenteral zinc supplementation, allowing for rapid re‐epithelialization of previously denuded skin.