中国急性间歇性卟啉病患者临床特点及治疗分析

背景目前我国急性间歇性卟啉病（AIP）的相关研究较少，大部分医务人员对其认识不足，极易导致误诊误治而延误病情。目的对公开发表的携带卟胆素原脱氨酶（HMBS）基因突变的中国AIP患者的临床资料进行整理分析，以提高医务工作者对AIP的认识。方法计算机检索PubMed及中国知网、万方数据知识服务平台、维普网，收集建库至2021-06-30所有公开发表的关于中国AIP病例的相关文献。由2名研究人员按照制定的纳入与排除标准对收集的文献进行筛选和数据提取。分析AIP患者一般情况、临床表现、实验室检查结果、治疗、基因突变情况。结果共纳入32篇文献、65例AIP患者，其中女56例、男9例，年龄集中在20~39岁〔83.1%（54/65）〕。AIP患者就诊原因多为腹痛〔63例（96.9%）〕，常伴有恶心、呕吐、便秘等症状。56.9%（37/65）的AIP患者出现中枢神经系统症状，如意识障碍（25例）、癫痫样发作（22例）、呼吸肌麻痹（6例）。13.8%（9/65）的AIP患者出现乏力（6例）、四肢麻木（4例）等外周神经系统症状。30.8%（20/65）的患者出现高血压、窦性心动过速等自主神经系统症状。9.2%（6/65）的患者出现抑郁、焦虑、幻觉等精神症状。35例曾多次经历过AIP的急性发作。部分患者的疾病发作可能与月经（9例）、妊娠和分娩（4例）、劳累（3例）、饮酒（2例）及节食（1例）有关。AIP患者中25例出现低钠血症，11例出现贫血，11例出现肝功能异常，6例出现肾功能异常，个别（1例）出现皮质醇节律的紊乱。27例AIP患者接受了糖负荷治疗，其中25例状况好转。2例接受了糖负荷联合血红素治疗，最终1例好转。本研究共纳入26个基因突变位点，其中突变位点p.R173W、p.R173Q、p.T269R、p.W283X、p.A330P可见于多例患者。对于同一突变类型患者也可表现出不同的临床表型。结论AIP临床表现复杂多变，病情严重程度具有异质性。当在临床上遇到不明原因腹痛、癫痫样发作、意识障碍、高血压、心动过速、低钠血症的患者，尤其是年轻女性患者，应警惕AIP的急性发作。目前我国临床上主要采用糖负荷治疗控制AIP的发作，而AIP临床表型的影响因素仍需进一步研究。

Clinical Characteristics and Treatment of Acute Intermittent Porphyria in Chinese Individuals

Background China's research on acute intermittent porphyria(AIP)is relatively limited.Due to most medical workers'insufficient understanding,AIP is easily misdiagnosed,and mistreated,leading to delayed appropriate treatment.Objective To analyze the clinical data of Chinese individuals with AIP with hydroxymethylbilane synthase(HMBS)gene mutation who were reported in published studies,improving medical workers'understanding of AIP.Methods Databases of PubMed,CNKI,Wanfang Data and CQVIP were searched for published articles about Chinese AIP cases from inception to June 30,2021.Literature screening based on the inclusion and exclusion criteria of this study and data extraction were performed by two researchers,separately.Information regarding general data,clinical manifestations,results of laboratory tests,treatments,and gene mutations of AIP patients was analyzed.Results A total of 32 articles were included,containing 65 AIP patients(56 females and 9 males)with the age mostly between 20-39 years old〔83.1%(54/65)〕.Most of AIP patients'admission were for abdominal pain〔63 cases(96.9%)〕,often accompanied by nausea,vomiting,and constipation.56.9%(37/65)of AIP patients suffered from central neuropathy,disturbance of consciousness(25 cases),epileptiform seizures(22 cases)and respiratory muscle paralysis(6 cases).13.8%(9/65)of patients experienced peripheral neuropathy including fatigue(6 cases)and limb numbness(4 cases).30.8%(20/65)of patients had autonomic neuropathy such as hypertension and tachycardia.9.2%(6/65)of patients experienced spirit symptoms,such as depression,anxiety and hallucination.Thirty-five patients had generated multiple acute attacks of AIP.In some patients,the onset of AIP may have been related to menstruation(9 cases),pregnancy and childbirth(4 cases),fatigue(3 cases),alcohol consumption(2 cases),and dieting(1 case).25 patients developed hyponatremia.There were 11 cases of anemia and 11 cases of abnormal liver function.Six patients were in abnormal renal function.1 case was caught in disorder of cortisol rhythm.Twenty-seven patients received carbohydrate loading therapy,and 25 of them were improved.Two patients were treated with carbohydrate loading combined with heme therapy,and 1 eventually improved.A total of 26 HMBS gene mutations were included in the study,where in the p.R173W,p.R173Q,p.T269R,p.W283X and p.A330P mutations were detected in multiple patients.And different patients with the same gene mutation may also show different clinical phenotypes.Conclusion AIP is a disease with complex and variable clinical manifestations and heterogeneous severity of disease.The acute attack of AIP should be considered if patients,especially young female patients,are clinically found to be with unexplained abdominal pain,epileptiform seizures,disturbance of consciousness,hypertension,tachycardia and hyponatremiain.Currently,carbohydrate loading therapy is mainly applied to control the attack of AIP in China.In terms of factors affecting the clinical phenotype of AIP,further exploration still needs to be carried out.