中国急性间歇性卟啉病患者的临床特点和致病基因分析:一项系统综述

Clinical features and pathogenic genes of patients with acute intermittent porphyria in China: a literature review

目的探讨我国急性间歇性卟啉病(AIP)患者的临床特点和致病基因。方法该研究为系统综述。以“acute intermittent porphyria”和“China”为英文检索词,以“急性间歇性卟啉病”为中文检索词在Pubmed、中国知网和万方数据知识服务平台中进行文献检索,检索时间为建库至2022年6月。纳入临床资料完整且发现羟甲基胆素合成酶(HMBS)基因突变的AIP病例,而后剔除重复病例。通过阅读文献收集纳入病例的临床特点和致病基因相关的资料。结果纳入48例来自32篇中外文献报道的中国AIP病例,分别来自37个家系。其中,女性45例(94%),发病年龄(26.8±6.5)岁;男性3例(6%),发病年龄分别为35、45和53岁。48个病例中首发症状为腹痛者47例(98%),伴恶心、呕吐、便秘和不完全肠梗阻,出现低钠血症者30例(63%)、脑病者29例(60%)、焦虑抑郁状态者24例(50%)、贫血者20例(42%)、癫痫发作者19例(40%)、肝功异常者19例(40%)、抗利尿激素分泌不当综合征者16例(33%),周围神经病者15例(31%),此外还有不同比例的患者出现心动过速、高血压或低血压、肌酐升高、低钾血症、发热和呼吸衰竭等临床表现。18例脑病患者进行了头颅MRI检查,其中11例(61%)提示可逆性后部脑病综合征。48例患者尿胆色素原均为阳性。48例AIP患者急性期均给予了高糖治疗,其中4例同时接受了高铁血红素制剂治疗,46例(96%)治疗有效。入选病例基因检测共发现30种HMBS基因突变,其中最常见的为c.517C>T(p.R173W)错义突变[9(19%)]。24个家系基因检测结果显示女性AIP外显率高于男性[分别为55%(24/44)和9%(1/11)]。结论我国AIP患者多为育龄期女性,常表现为反复发作的多脏器损害,急性期高糖治疗有效,且致病基因突变具有多样性。

Objective To analyze the clinical features and pathogenic genes of patients with acute intermittent porphyria(AIP)in China.Methods This was a systematic review.PubMed,CNKI and Wanfang Data were researched by using the terms“acute intermittent porphyria”and“China”from inception to June,2022.The Chinese AIP patients with complete clinical data and hydroxymethylbilane synthase(HMBS)gene findings were collected and analyzed.The duplicated AIP cases were deleted.Results Total 48 AIP cases of 37 families were collected from 32 studies.Among them,45 cases(94%)were females with a symptom onset age of(26.8±6.5)years,and 3 cases(6%)were males with an onset age of 35,45 and 53 years,respectively.Forty-seven cases(98%)had initial symptom of abdominal pain,accompanied with nausea,vomiting and incomplete intestinal obstruction;30(63%)had hyponatremia,29(60%)had encephalopathy;24(50%)had anxiety and/or depression;20(42%)had anemia;19(40%)had epilepsy;19(40%)had abnormal liver function;16(33%)had inappropriate antidiuretic hormone secretion syndrome;15(31%)had symmetric motor predominant neuropathy;and various proportions of patients presented with tachycardia,hypertension or hypotension,increased serum creatinine,hypokalemia,fever and respiratory failure.Among 18 AIP patients with encephalopathy,brain MRI showed posterior reversible encephalopathy syndrome in 11 cases(61%).Urine porphobilinogen(PBG)was positive in all patients during the acute attacks.All patients received intravenous infusion of high dose glucose,and 4 received intravenous infusion of heme simultaneously;96%(46/48)patients had remission.Thirty mutations were detected in HMBS gene.The penetrance analysis on 24 AIP families with HMBS gene mutation revealed that the penetrance rate in females was higher than that in males(55%(24/44)vs.9%(1/11)).Conclusions AIP is more common in females during the reproductive period.AIP frequently involves multiple systems.Treatment with intravenous infusion of high dose glucose and heme is effective.Thirty HMBS gene mutations have been identified in these 48 Chinese AIP patients.