Long-term neurological outcome of a cohort of 80 patients with classical organic acidurias.
Long-term neurological outcome of a cohort of 80 patients with classical organic acidurias.
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DOI：
10.1186/1750-1172-8-148
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发表时间：
2013-09-23
影响因子：
3.7
通讯作者：
de Lonlay P
中科院分区：
文献类型：
--
作者：
Nizon M;Ottolenghi C;Valayannopoulos V;Arnoux JB;Barbier V;Habarou F;Desguerre I;Boddaert N;Bonnefont JP;Acquaviva C;Benoist JF;Rabier D;Touati G;de Lonlay P
经典的有机酸尿症包括甲基丙二酸尿症（MMA）、丙酸尿症（PA）和异戊酸尿症（IVA），是支链氨基酸和奇数链脂肪酸代谢的严重先天性缺陷，并伴有严重的并发症。本研究通过整合临床、放射学、生化和遗传学数据，调查了80例经典有机酸尿症患者（38例MMA，24例PA和18例IVA）的长期结局。患者平均随访14年[年龄3.3-46.3岁]。PA包括更多神经系统检查异常的患者（PA为37%，MMA为24%，IVA为0%）、较低的心理测量评分（61%的PA患者在3岁时评估异常，MMA为26%，IVA为18%）和更频繁的基底节病变（56%的患者，MMA为36%，IVA为17%）。所有IVA患者的神经系统检查均正常，只有1/3的患者出现认知障碍。MMA的预后为中等。排除急性失代偿的生化代谢物分析显示甘氨酸、丙氨酸和谷氨酰胺显著进行性增加，特别是在PA中，可能在MMA中，但与神经学结局无关。在MMA智力缺陷患者中发现血浆甲基丙二酸显著升高（平均水平为199 μmol/L vs 70 μmol/L，p < 0.05），估计出生至6岁之间的平均水平高于167 μmol/L有显著的严重结局概率。患有智力缺陷的PA患者的尿3-羟基丙酸（3-HP）水平显着较高（平均肌酸酐水平为68.9 μmol/mmol，而肌酸酐水平为34.6 μmol/mmol，p < 0.01），估计出生至6岁期间的平均水平高于55 μmol/mmol时出现严重结局的可能性很大。至于分子分析，涉及MMAA基因突变的MMA患者的预后比涉及MUT基因突变的患者更好。丙酸尿症有最严重的神经系统预后。我们的放射学和生化数据与线粒体毒性机制一致。随访血浆MMA和尿3-HP水平可能具有预后意义，需要更大的努力来优化这些患者的长期管理。
Classical organic acidurias including methylmalonic aciduria (MMA), propionic aciduria (PA) and isovaleric aciduria (IVA) are severe inborn errors of the catabolism of branched-chain amino acids and odd-numbered chain fatty acids, presenting with severe complications. This study investigated the long-term outcome of 80 patients with classical organic aciduria (38 with MMA, 24 with PA and 18 with IVA) by integrating clinical, radiological, biochemical and genetic data. Patients were followed-up for a mean of 14 years [age 3.3-46.3 years]. PA included a greater number of patients with abnormal neurological examination (37% in PA, 24% in MMA and 0% in IVA), lower psychometric scores (abnormal evaluation at age 3 years in 61% of patients with PA versus 26% in MMA and 18% in IVA) and more frequent basal ganglia lesions (56% of patients versus 36% in MMA and 17% in IVA). All patients with IVA presented a normal neurological examination and only 1/3 presented cognitive troubles. Prognosis for MMA was intermediate. Biochemical metabolite analysis excluding acute decompensations revealed significant progressive increases of glycine, alanine and glutamine particularly in PA and possibly in MMA but no correlation with neurological outcome. A significant increase of plasma methylmalonic acid was found in MMA patients with intellectual deficiency (mean level of 199 μmol/L versus 70 μmol/L, p < 0.05), with an estimated significant probability of severe outcome for average levels between birth and age 6 years above 167 μmol/L. Urinary 3-hydroxypropionate (3-HP) levels were significantly higher in PA patients with intellectual deficiency (mean level of 68.9 μmol/mmol of creatinine versus 34.6 μmol/mmol of creatinine, p < 0.01), with an estimated significant probability of severe outcome for average levels between birth and age 6 years above 55 μmol/mmol. As for molecular analysis, prognosis of MMA patients with mutations involving the MMAA gene was better compared to patients with mutations involving the MUT gene. Propionic aciduria had the most severe neurological prognosis. Our radiological and biochemical data are consistent with a mitochondrial toxicity mechanism. Follow-up plasma MMA and urinary 3-HP levels may have prognostic significance calling for greater efforts to optimize long-term management in these patients.
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影响因子：
3.8
作者：
Cosson, M. A.;Touati, G.;de Lonlay, P.
通讯作者：
de Lonlay, P.
DOI：
10.1002/ajmg.c.30090
发表时间：
2006-05-15
影响因子：
3.1
作者：
Deodato, F;Boenzi, S;Dionisi-Vici, C
通讯作者：
Dionisi-Vici, C
影响因子：
4.2
作者：
de Baulny, HO;Benoist, JF;Saudubray, JM
通讯作者：
Saudubray, JM
影响因子：
4.8
作者：
Okun, JG;Hörster, F;Kölker, S
通讯作者：
Kölker, S
影响因子：
3.6
作者：
de Keyzer, Yves;Valayannopoulos, Vassili;de Lonlay, Pascale
通讯作者：
de Lonlay, Pascale