Waisbren Susan E, Landau Yuval, Wilson Jenna, Vockley Jerry
Department of Psychology, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA.
Dev Disabil Res Rev. 2013;17(3):260-8. doi: 10.1002/ddrr.1119.
Mitochondrial fatty acid oxidation disorders include conditions in which the transport of activated acyl-Coenzyme A (CoA) into the mitochondria or utilization of these substrates is disrupted or blocked. This results in a deficit in the conversion of fat into energy. Most patients with fatty acid oxidation defects are now identified through newborn screening by tandem mass spectrometry. With earlier identification and preventative treatments, mortality and morbidity rates have improved. However, in the absence of severe health and neurological effects from these disorders, subtle developmental delays or neuropsychological deficits have been noted. Medical records were reviewed to identify outcomes in 85 children with FAOD's diagnosed through newborn screening and followed at one metabolic center. Overall, 54% of these children identified through newborn screening experienced developmental challenges. Speech delay or relative weakness in language was noted in 26 children (31%) and motor delays were noted in 24 children (29%). The majority of the 46 children receiving psychological evaluations performed well within the average range, with only 11% scoring <85 on developmental or intelligence tests. These results highlight the importance of screening children with fatty acid oxidation disorders to identify those with language, motor, or cognitive delay. Although expanded newborn screening dramatically changes the health and developmental outcomes in many children with fatty acid oxidation disorders, it also complicates the interpretation of biochemical and molecular findings and raises questions about the effectiveness or necessity of treatment in a large number of cases. Only by systematically evaluating developmental and neuropsychological outcomes using standardized methods will the true implications of newborn screening, laboratory results, and treatments for neurocognitive outcome in these disorders become clear.
活化的酰基辅酶A（CoA）进入线粒体的转运过程或这些底物的利用过程受到破坏或阻碍。这导致脂肪转化为能量的过程出现缺陷。现在，大多数患有脂肪酸氧化缺陷的患者是通过串联质谱法进行新生儿筛查而被确诊的。随着早期诊断和预防性治疗的开展，死亡率和发病率有所改善。然而，在这些疾病没有产生严重健康和神经影响的情况下，已注意到存在细微的发育迟缓或神经心理缺陷。回顾了医疗记录，以确定在一个代谢中心接受随访的85名通过新生儿筛查确诊为脂肪酸氧化障碍（FAOD）的儿童的预后情况。总体而言，通过新生儿筛查确诊的这些儿童中有54%经历了发育方面的挑战。26名儿童（31%）存在语言发育迟缓或语言相对薄弱的情况，24名儿童（29%）存在运动发育迟缓的情况。在接受心理评估的46名儿童中，大多数在平均范围内表现良好，只有11%在发育或智力测试中的得分低于85分。这些结果凸显了对患有脂肪酸氧化障碍的儿童进行筛查以确定那些存在语言、运动或认知发育迟缓的儿童的重要性。尽管扩大新生儿筛查极大地改变了许多患有脂肪酸氧化障碍儿童的健康和发育结局，但它也使生化和分子检测结果的解读变得复杂，并在大量病例中引发了关于治疗有效性或必要性的问题。只有通过使用标准化方法系统地评估发育和神经心理结局，这些疾病中新生儿筛查、实验室结果及治疗对神经认知结局的真正影响才会变得清晰。
