von Kleist-Retzow Jürgen-Christoph, Cormier-Daire Valérie, Viot Géraldine, Goldenberg Alice, Mardach Becky, Amiel Jeanne, Saada Philippe, Dumez Yves, Brunelle Francis, Saudubray Jean-Marie, Chrétien Dominique, Rötig Agnès, Rustin Pierre, Munnich Arnold, De Lonlay Pascale
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Hôpital des Enfants-Malades, 149 Rue de Sèvres, 75743 Paris Cedex 15, France.
J Pediatr. 2003 Aug;143(2):208-12. doi: 10.1067/S0022-3476(03)00130-6.
To review the antenatal manifestations of disorders of oxidative phosphorylation.
A total of 300 cases of proven respiratory chain enzyme deficiency were retrospectively reviewed for fetal development, based on course and duration of pregnancy, antenatal ultrasonography and birth weight, length, and head circumference. Particular attention was given to fetal movements, oligo/hydramnios, fetal cardiac rhythm, fetal heart ultrasound, and ultrasonography/echo Doppler signs of brain, facial, trunk, limb, and organ anomalies.
Retrospective analyses detected low birth weight (<3rd percentile for gestational age) in 22.7% of cases (68/300, P<.000001). Intrauterine growth retardation was either isolated (48/300, 16%) or associated with otherwise unexplained anomalies (20/300, 6.7%, P<.0001). Antenatal anomalies were usually multiple and involved several organs sharing no common function or embryologic origin. They included polyhydramnios (6/20), oligoamnios (2/20), arthrogryposis (1/20), decreased fetal movements (1/20), ventricular septal defects (2/20), hypertrophic cardiomyopathy (4/20), cardiac rhythm anomalies (4/20), hydronephrosis (3/20), vertebral abnormalities, anal atresia, cardiac abnormalities, tracheoesophageal fistula/atresia, renal agenesis and dysplasia, and limb defects (VACTERL) association (2/20), and a complex gastrointestinal malformation (1/20).
Although a number of metabolic diseases undergo a symptom-free period, respiratory chain deficiency may have an early antenatal expression, presumably related to the time course of the disease gene expression in the embryofetal period. The mechanism triggering malformations is unknown and may include decreased ATP formation and/or an alteration of apoptotic events controlled by the mitochondria.
回顾氧化磷酸化障碍的产前表现。
对300例经证实的呼吸链酶缺乏病例进行回顾性研究，根据妊娠过程和持续时间、产前超声检查以及出生体重、身长和头围评估胎儿发育情况。特别关注胎动、羊水过少/过多、胎儿心律、胎儿心脏超声以及脑、面部、躯干、四肢和器官异常的超声检查/回声多普勒征象。
回顾性分析发现，22.7%的病例（68/300，P<0.000001）出生体重低（低于孕周的第3百分位数）。宫内生长受限要么是孤立的（48/300，16%），要么与其他不明原因的异常相关（20/300，6.7%，P<0.0001）。产前异常通常是多发性的，累及多个无共同功能或胚胎学起源的器官。这些异常包括羊水过多（6/20）、羊水过少（2/20）、关节挛缩（1/20）、胎动减少（1/20）、室间隔缺损（2/20）、肥厚型心肌病（4/20）、心律异常（4/20）、肾积水（3/20）、椎体异常、肛门闭锁、心脏异常、气管食管瘘/闭锁、肾缺如和发育不全以及肢体缺陷（VACTERL）综合征（2/20），还有一种复杂的胃肠道畸形（1/20）。
尽管许多代谢性疾病有一段无症状期，但呼吸链缺乏可能在产前早期就有表现，推测与胚胎胎儿期疾病基因表达的时间进程有关。引发畸形的机制尚不清楚，可能包括ATP生成减少和/或线粒体控制的凋亡事件改变。
