720例甲基丙二酸血症MMACHC基因c.609G>A突变患者临床特征及随访分析

R725.8; 目的:分析携带MMACHC基因c.609G>A(p.W203X)突变的cblC型甲基丙二酸血症(MMA)患者的临床表现、治疗效果、预后及影响因素.方法:回顾性分析2007至2020年在上海交通大学医学院附属新华医院就诊的720例携带c.609G>A突变的cblC型MMA患者的临床及实验室检查资料.根据基因突变位点不同将患者分为三组,携带c.609G>A纯合突变的患者为A组(172例);携带c.609G>A与c.482G>A(p.R161Q)、c.80A>G(p.Q27R)及c.394C>T(p.R132X)中任一突变形成的复合杂合突变患...

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Published inZhejiang da xue xue bao. Journal of Zhejiang University. Medical sciences. Yi xue ban Vol. 50; no. 4; pp. 436 - 443
Main Authors 于玥, 凌诗颖, 帅瑞雪, 邱文娟, 张惠文, 梁黎黎, 季文君, 刘宇超, 顾学范, 韩连书
Format Journal Article
LanguageChinese
English
Published 上海交通大学医学院附属新华医院 上海市儿科医学研究所小儿内分泌遗传代谢科,上海200092 01.08.2021
Zhejiang University Press
Subjects
新生儿筛查;甲基丙二酸血症;MMACHC基因;钴胺素C缺乏;预后;影响因素
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ISSN1008-9292
DOI10.3724/zdxbyxb-2021-0276

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Abstract R725.8; 目的:分析携带MMACHC基因c.609G>A(p.W203X)突变的cblC型甲基丙二酸血症(MMA)患者的临床表现、治疗效果、预后及影响因素.方法:回顾性分析2007至2020年在上海交通大学医学院附属新华医院就诊的720例携带c.609G>A突变的cblC型MMA患者的临床及实验室检查资料.根据基因突变位点不同将患者分为三组,携带c.609G>A纯合突变的患者为A组(172例);携带c.609G>A与c.482G>A(p.R161Q)、c.80A>G(p.Q27R)及c.394C>T(p.R132X)中任一突变形成的复合杂合突变患者为B组(169例);携带c.609G>A与上述突变位点以外突变[如c.658_660delAAG(p.K220del)、c.315A>T(p.Y105X)、c.567dupT(p.I190fs*13)]的复合杂合突变患者为C组(379例).对不同基因突变位点患者的临床表现,血酰基肉碱、血同型半胱氨酸、尿有机酸水平以及治疗效果进行比较,根据随访结果采用logistic回归分析患者预后的影响因素.结果:720例患者中306例(42.5％)来自新生儿筛查,其中156例发病;414例未进行新生儿筛查的患者中10例因同胞确诊后诊断(临床未发病),其余404例均为临床发病病例.560例发病患者中,发病年龄中位数为1.2个月(3 d～20岁).B组发病年龄晚于A组和C组,三组间发病年龄差异有统计学意义(P<0.01).患者临床症状各异,1岁以内发病患者多表现为呕吐、腹泻、喂养困难及抽搐,1岁以后发病患者多以运动障碍及智力落后为主要表现.肾脏疾病起病的患者均携带c.80A>G或c.482G>A突变,伴有肺动脉高压的患者均携带c.80A>G突变.长期随访患者621例,其中预后正常156例(25.1％),落后433例(69.7％),死亡32例(5.2％).剔除失访、死亡及资料缺失的患者,对559例患者的预后影响因素进行logistic回归分析,结果显示新生儿筛查与否、发病与否、发病年龄及基因突变位点对预后的影响有统计学意义(P<0.05或P<0.01).结论:MMACHC基因c.609G>A突变与早发型MMA相关,患者多于出生后1个月内起病.维生素B12肌内注射对携带不同突变的患者均有效.新生儿筛查对患者预后有益,而临床发病则不利于患者预后,携带c.609G>A纯合突变患者较携带c.
AbstractList R725.8; 目的:分析携带MMACHC基因c.609G>A(p.W203X)突变的cblC型甲基丙二酸血症(MMA)患者的临床表现、治疗效果、预后及影响因素.方法:回顾性分析2007至2020年在上海交通大学医学院附属新华医院就诊的720例携带c.609G>A突变的cblC型MMA患者的临床及实验室检查资料.根据基因突变位点不同将患者分为三组,携带c.609G>A纯合突变的患者为A组(172例);携带c.609G>A与c.482G>A(p.R161Q)、c.80A>G(p.Q27R)及c.394C>T(p.R132X)中任一突变形成的复合杂合突变患者为B组(169例);携带c.609G>A与上述突变位点以外突变[如c.658_660delAAG(p.K220del)、c.315A>T(p.Y105X)、c.567dupT(p.I190fs*13)]的复合杂合突变患者为C组(379例).对不同基因突变位点患者的临床表现,血酰基肉碱、血同型半胱氨酸、尿有机酸水平以及治疗效果进行比较,根据随访结果采用logistic回归分析患者预后的影响因素.结果:720例患者中306例(42.5％)来自新生儿筛查,其中156例发病;414例未进行新生儿筛查的患者中10例因同胞确诊后诊断(临床未发病),其余404例均为临床发病病例.560例发病患者中,发病年龄中位数为1.2个月(3 d～20岁).B组发病年龄晚于A组和C组,三组间发病年龄差异有统计学意义(P<0.01).患者临床症状各异,1岁以内发病患者多表现为呕吐、腹泻、喂养困难及抽搐,1岁以后发病患者多以运动障碍及智力落后为主要表现.肾脏疾病起病的患者均携带c.80A>G或c.482G>A突变,伴有肺动脉高压的患者均携带c.80A>G突变.长期随访患者621例,其中预后正常156例(25.1％),落后433例(69.7％),死亡32例(5.2％).剔除失访、死亡及资料缺失的患者,对559例患者的预后影响因素进行logistic回归分析,结果显示新生儿筛查与否、发病与否、发病年龄及基因突变位点对预后的影响有统计学意义(P<0.05或P<0.01).结论:MMACHC基因c.609G>A突变与早发型MMA相关,患者多于出生后1个月内起病.维生素B12肌内注射对携带不同突变的患者均有效.新生儿筛查对患者预后有益,而临床发病则不利于患者预后,携带c.609G>A纯合突变患者较携带c.
Author 邱文娟
顾学范
季文君
张惠文
刘宇超
韩连书
梁黎黎
于玥
帅瑞雪
凌诗颖
AuthorAffiliation 上海交通大学医学院附属新华医院 上海市儿科医学研究所小儿内分泌遗传代谢科,上海200092
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Author_FL SHUAI Ruixue
LING Shiying
HAN Lianshu
QIU Wenjuan
ZHANG Huiwen
YU Yue
JI Wenjun
LIU Yuchao
GU Xuefan
LIANG Lili
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2021 Zhejiang University Press
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DocumentTitle_FL Clinical features and outcomes of patients with cblC type methylmalonic acidemia carrying MMACHC gene c.609G>A mutation
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Keywords 新生儿筛查;甲基丙二酸血症;MMACHC基因;钴胺素C缺乏;预后;影响因素
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Notes 第一作者：于　玥，硕士研究生，主要从事甲基丙二酸血症相关研究；E-mail：yuyue0524@sjtu.edu.cn；https：//orcid.org/0000-0002-2617-459X
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Zhejiang University Press
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Title 720例甲基丙二酸血症MMACHC基因c.609G>A突变患者临床特征及随访分析
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