ALDOB基因复合杂合变异致遗传性果糖不耐受饮食控制30年1例报告并文献复习  

Report of an inherited fructose intolerance case under 30 years diet control caused by ALDOB compound heterozygous mutations and literature review

作　　者：秦谦 陈乡 卢宇蓝[1] 吴冰冰[1] 王慧君[1] 董欣然 杨琳[3] 周文浩[1,2,3] QIN Qian;CHEN Xiang;LU Yu-lan;WU Bing-bing;WANG Hui-jun;DONG Xin-ran;YANG Lin;ZHOU Wen-hao(Children's Hospital of Fudan University,Center of Molecular Medicine,Shanghai 201102,China;Department of Neonatology Children's Hospital of Fudan University,Shanghai 201102,China;Clinical Genetic Center,Children's Hospital of Fudan University,Shanghai 201102,China)

机构地区：[1]复旦大学附属儿科医院分子医学中心,上海201102 [2]复旦大学附属儿科医院新生儿科,上海201102 [3]复旦大学附属儿科医院临床遗传中心,上海201102

出　　处：《中国循证儿科杂志》2018年第4期269-274,共6页Chinese Journal of Evidence Based Pediatrics

基　　金：2016国家重点研发计划精准医学专项:2016YFC0905102

摘　　要：目的总结1例ALDOB基因复合杂合变异致遗传性果糖不耐受(HFI)患者饮食控制30年的远期随访结局和饮食控制经验。方法回顾性总结1例ALDOB基因复合杂合变异致HFI初诊时的临床资料、30年饮食控制经历、基因检查结果和远期随访结局,系统筛选和记录能引起患者症状的食谱。复习文献,总结HGMD数据库收录为ALDOB致病变异、同时有详细临床信息的HFI患者的临床资料,分析饮食控制与未控制的随访结局。结果女,4岁,因"不明原因低热,呕吐后症状缓解"就诊。生后20 d开始添加奶粉,喂养后立即呕吐,改为米粥喂养,呕吐症状缓解。儿童期食西瓜、蛋糕等后出现呕吐症状,开始停止摄入含糖类食物。7岁时曾以"吃甜食后低热、饥饿感、呕吐后可缓解"就诊,曾诊断"生长发育不良,遗传代谢性疾病待查",家属开始系统筛选和记录能引起患儿呕吐症状的水果、蔬菜等食物。目前随访至30岁,身高174.6 cm,体重57.6 kg,智力发育正常,心、肺、甲状腺、肝、肾功能未见异常。WGS检测及家系Sanger验证,发现ALDOB基因复合杂合变异[NM_000035,exon4:c.360_363delCAAA(p.N120Kfs*32); exon9:c.1013C>T (p.A338V)],A338V来自父亲,N120Kfs*32来自母亲。HGMD数据库收录为ALDOB基因致病变异、同时有临床信息的HFI患者33例,未控制饮食患者预后不良比例[75%(6/8)]高于饮食控制患者[50%(9/18)]。控制饮食但仍出现预后不良的患者中,移码变异占55. 6%,高于控制饮食后未出现预后不良的患者(27.8%)。结论饮食控制对HFI的改善预后具有重要意义,但携带移码变异的患者在控制饮食的情况下仍可能有不良预后,需要更为严格的饮食控制并密切随访。Objective A patient with fructose intolerance(HFI)with ALDOB compound heterozygous mutations was identified,and the follow-up data for 30 years was summarized.Methods The clinical manifestation and the experience of diet control were retrospectively summarized,and the gene sequencing results and the long-term outcome were also reported.The recipes that could cause HFI symptoms in the patient were systematically selected and recorded.The clinical information of patients with the known pathogenic mutations of ALDOB gene in HGMD was collected through literature review,the potential relationship between diet control and follow-up outcome was analyzed in patients with detailed clinical information.Results A 4-year-old girl suffered from fever due to unknown reasons,and the symptoms were relieved after vomiting.From the 20th day after birth,vomiting was observed immediately after the milk feeding.After changing to rice porridge,vomiting symptom was alleviated.In the childhood,due to the observation that the patient would vomit after eating foods like watermelon and cakes,the intake of sugary foods was avoided.At the age of 7 years,the patient was diagnosed as"developmental delay,inherited metabolic disorder?"with the chief complaints of low-fever,hunger after eating sweet foods and vomiting could relieve the symptoms.Meanwhile,parents started to select and record fruits,vegetables and other foods that could cause vomiting.The patient was followed up to 30 years old,with the height of 174.6 cm,the weight of 57.6 kg,normal intellectual development.No abnormalities were observed in heart,lung,thyroid,liver and kidney functions.The patient summarized detailed dietary contraindications and expected to perform genetic testing to identify the inherited metabolic diseases for diagnosis.The patient was tested by whole genome sequencing and Sanger validation and it turned out that she carried compound heterozygous mutations of ALDOB gene[NM_000035,exon4:c.360_363delCAAA(p.N120Kfs*32);exon9:c.1013C>T(p.A338V)].A338V was inherited

关 键 词：果糖不耐受 全基因组序列分析 表型基因型关联性 

分 类 号：R725.9[医药卫生—儿科]