Barret Béatrice, Tardieu Marc, Rustin Pierre, Lacroix Catherine, Chabrol Brigitte, Desguerre Isabelle, Dollfus Catherine, Mayaux Marie-Jeanne, Blanche Stéphane
INSERM U569 (Epidémiologie, Démographie et Sciences Sociales) Hôpital Bicêtre AP-HP, Le Kremlin Bicêtre, France.
AIDS. 2003 Aug 15;17(12):1769-85. doi: 10.1097/00002030-200308150-00006.
Antiretroviral prevention of mother to child HIV-1 is established but tolerance remains to be assessed. AIM To determine the risk for persistent mitochondrial dysfunction in HIV-uninfected children born to seropositive mothers.
An exhaustive study in a large prospective cohort with predetermined algorithm of the unexplained symptoms compatible with mitochondrial dysfunction. A total of 2644 of 4392 children were exposed to antiretrovirals. Complementary investigations were carried out on a case-by-case basis using classification with a diagnostic probability scale, based on experience with constitutional diseases. A spontaneous notification register for children not included in the cohort was created.
Good circumstantial evidence of mitochondrial dysfunction was found for twelve children. Seven were from the cohort. All presented neurological symptoms, often associated with abnormal magnetic resonance image (10 of 12) and/or a significant episode of hyperlactatemia (seven of 12). All had either a profound deficit in one of the respiratory chain complexes (11 of 12) and/or a typical histological pattern (two of 12). All were perinatally exposed to antiretrovirals. None of them had perinatal morbidity that could explain this symptomatology. The 18-month incidence was 0.26% (95% confidence interval, 0.10-0.54) in exposed children, in comparison with the general figure of 0.01% for paediatric neuro-mitochondrial diseases in the general population. Fourteen other children in the cohort, all exposed to antiretrovirals, had unexplained symptoms, mostly neurological, for which one of the possible differential diagnoses was mitochondrial dysfunction. Close similarities in clinical, neuroradiological and histological findings strongly suggest a common pathological process in all these 26 children.
Children exposed to nucleoside analogues during the perinatal period are at risk of a neurological syndrome associated with persistent mitochondrial dysfunction.
抗逆转录病毒药物预防母婴传播HIV-1已得到确立，但耐受性仍有待评估。目的：确定血清学阳性母亲所生未感染HIV儿童出现持续性线粒体功能障碍的风险。
在一个大型前瞻性队列中进行详尽研究，采用针对与线粒体功能障碍相符的不明原因症状的预定算法。4392名儿童中有2644名暴露于抗逆转录病毒药物。根据体质性疾病的经验，使用诊断概率量表分类，对每个病例进行补充调查。为未纳入队列的儿童创建了一个自发报告登记册。
发现12名儿童有良好的线粒体功能障碍间接证据。其中7名来自队列。所有儿童均出现神经症状，常伴有异常磁共振成像（12例中的10例）和/或严重高乳酸血症发作（12例中的7例）。所有儿童均存在呼吸链复合物之一严重缺陷（12例中的11例）和/或典型组织学模式（12例中的2例）。所有儿童围产期均暴露于抗逆转录病毒药物。他们均无围产期发病率可解释这种症状。暴露儿童的18个月发病率为0.26%（95%置信区间，0.10 - 0.5...
