女性患儿，11岁，因反复全身及黏膜部位皮疹10年入院，典型皮疹为口周、手足关节、外阴、肛周处红斑，红斑上可见水疱、糜烂、溃疡，补锌治疗后好转，其弟弟有类似的皮疹及病史。皮肤组织病理学检查可见表皮角化不全伴轻度角化过度，角质层重度海绵状水肿，棘细胞明显增生，角质形成细胞空泡化。基因检测提示患儿及其弟弟SLC39A4基因均存在c.1456(exon9)delG致病性纯合突变，诊断为肠病性肢端皮炎。对于反复出现四肢及腔口周围皮疹，且治疗反复的患儿，应尽早完善基因检测以明确诊断，同时予以足剂量的补锌治疗，定期检测血清锌等微量元素的水平。 ［中国当代儿科杂志，2022，24（9）：1047-1052］
Abstract
A girl, aged 11 years, was admitted due to recurrent rash on the whole body and mucosa for 10 years, and typical rash was erythema at the perioral region, hand-foot joints, vulva, and perianal region, with blisters, erosions, and ulcers on the erythema. The girl was improved after zinc supplementation. Her younger brother had similar rash and medical history. The histopathological examination showed epidermal parakeratosis with mild hyperkeratosis, severe spongiform edema of the stratum corneum, significant proliferation of acanthocytes, and vacuolation of keratinocytes. The genetic testing revealed that both the girl and her younger brother had a homozygous mutation of c.1456(exon9)delG in the SLC39A4 gene, and thus the girl was diagnosed with acrodermatitis enteropathica. It is concluded that for children with recurrent rash on the limbs and at the perioral region, genetic testing should be performed as early as possible to make a confirmed diagnosis, and a sufficient dose of zinc supplementation should be given, while the levels of trace elements such as blood zinc should be regularly monitored. Citation:Chinese Journal of Contemporary Pediatrics, 2022, 24(9): 1047-1052
关键词
肠病性肢端皮炎 /
SLC39A4 /
基因突变 /
儿童
Key words
Acrodermatitis enteropathica /
SLC39A4 /
Gene mutation /
Child
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
1 Maverakis E, Fung MA, Lynch PJ, et al. Acrodermatitis enteropathica and an overview of zinc metabolism[J]. J Am Acad Dermatol, 2007, 56(1): 116-124. PMID: 17190629. DOI: 10.1016/j.jaad.2006.08.015.
2 王红梅, 吴沪生. 生物素缺乏症18例临床研究[J]. 中国实用儿科杂志, 2010, 25(11): 874-876.
3 李珂瑶, 文容, 罗鸯鸯, 等. Netherton综合征一例[J]. 实用皮肤病学杂志, 2021, 14(6): 379-381. DOI: 10.11786/sypfbxzz.1674-1293.20210617.
4 张振华, 王召阳, 徐子刚. 儿童银屑病诊疗进展[J]. 皮肤科学通报, 2022, 39(2): 115-120.
5 甘川, 许红梅. 5例STAT1功能获得性基因突变儿童慢性皮肤黏膜念珠菌病临床特点及生化免疫分析[J]. 临床儿科杂志, 2019, 37(10): 739-743. DOI: 10.3969/j.issn.1000-3606.2019.10.005.
6 王秋菊, 沈亦平, 邬玲仟, 等. 遗传变异分类标准与指南[J]. 中国科学(生命科学), 2017, 47(6): 668-688. DOI: 10.1360/N052017-00099.
7 Ogawa Y, Kinoshita M, Shimada S, et al. Zinc and skin disorders[J]. Nutrients, 2018, 10(2): 199. PMID: 29439479. PMCID: PMC5852775. DOI: 10.3390/nu10020199.
8 牟韵竹, 张正中, 杨萍, 等. 一例肠病性肢端皮炎患者的SLC39A4基因突变研究[J]. 中华医学遗传学杂志, 2017, 34(3): 387-389. PMID: 28604961. DOI: 10.3760/cma.j.issn.1003-9406.2017.03.016.
9 Danbolt N, Closs K. Acrodermatitis enteropathica[J]. Acta Derm Venereol, 1942, 23: 127-169.
10 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[J]. Mol Cell Biol, 2009, 29(1): 129-139. PMID: 18936158. PMCID: PMC2612479. DOI: 10.1128/MCB.00963-08.
11 Kambe T, Fukue K, Ishida R, et al. Overview of inherited zinc deficiency in infants and children[J]. J Nutr Sci Vitaminol (Tokyo), 2015, 61 Suppl: S44-S46. PMID: 26598882. DOI: 10.3177/jnsv.61.S44.
12 Corbo MD, Lam J. Zinc deficiency and its management in the pediatric population: a literature review and proposed etiologic classification[J]. J Am Acad Dermatol, 2013, 69(4): 616-624.e1. PMID: 23688650. DOI: 10.1016/j.jaad.2013.04.028.
13 Livingstone C. Zinc: physiology, deficiency, and parenteral nutrition[J]. Nutr Clin Pract, 2015, 30(3): 371-382. PMID: 25681484. DOI: 10.1177/0884533615570376.
14 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]. J Trace Elem Med Biol, 2015, 29: 47-62. PMID: 25468189. DOI: 10.1016/j.jtemb.2014.10.003.
15 王小伶, 尚盼盼, 付希安, 等. 一例锌缺乏患者的SLC39A4基因突变检测并文献复习[J]. 中国麻风皮肤病杂志, 2019, 35(1): 17-19.
16 Gehrig KA, Dinulos JG. Acrodermatitis due to nutritional deficiency[J]. Curr Opin Pediatr, 2010, 22(1): 107-112. PMID: 19966568. DOI: 10.1097/MOP.0b013e328335107f.
17 Antonelli E, Bassotti G, Tramontana M, et al. Dermatological manifestations in inflammatory bowel diseases[J]. J Clin Med, 2021, 10(2): 364. PMID: 33477990. PMCID: PMC7835974. DOI: 10.3390/jcm10020364.
18 Glutsch V, Hamm H, Goebeler M. Zinc and skin: an update[J]. J Dtsch Dermatol Ges, 2019, 17(6): 589-596. PMID: 30873720. DOI: 10.1111/ddg.13811.
19 周欣, 薛如君, 罗权, 等. 肠病性肢端皮炎SLC39A4基因突变[J]. 中国皮肤性病学杂志, 2020, 34(7): 739-742. DOI: 10.13735/j.cjdv.1001-7089.201909054.
20 Kilic SS, Giraud M, Schmitt S, et al. A novel mutation of the SLC39A4 gene causing acrodermatitis enteropathica[J]. Br J Dermatol, 2007, 157(2): 386-387. PMID: 17573886. DOI: 10.1111/j.1365-2133.2007.08000.x.
21 Lakdawala N, Grant-Kels JM. Acrodermatitis caused by nutritional deficiency and metabolic disorders[J]. Clin Dermatol, 2017, 35(1): 64-67. PMID: 27938814. DOI: 10.1016/j.clindermatol.2016.09.009.
22 杜姿岑, 张正中. 肠病性肢端皮炎研究进展[J]. 中国皮肤性病学杂志, 2019, 33(3): 347-350. DOI: 10.13735/j.cjdv.1001-7089.201803160.
23 Küry S, Kharfi M, Blouin E, et al. Clinical utility gene card for: acrodermatitis enteropathica—update 2015[J]. Eur J Hum Genet, 2016, 24(5): 779. PMID: 26443269. PMCID: PMC4930100. DOI: 10.1038/ejhg.2015.203.
24 Zhong W, Yang C, Zhu L, et al. Analysis of the relationship between the mutation site of the SLC39A4 gene and acrodermatitis enteropathica by reporting a rare Chinese twin: a case report and review of the literature[J]. BMC Pediatr, 2020, 20(1): 34. PMID: 31987033. PMCID: PMC6983971. DOI: 10.1186/s12887-020-1942-4.
PDF(942 KB)
