Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon, USA.
OHSU-PSU School of Public Health, Biostatistics, Oregon Health & Science University, Portland, Oregon, USA.
J Inherit Metab Dis. 2024 Jul;47(4):746-756. doi: 10.1002/jimd.12738. Epub 2024 Apr 16.
Long chain 3-hydroxyacyl-CoA dehydrogenase (LCHADD) is the only fatty acid oxidation disorder to develop a progressive chorioretinopathy resulting in vision loss; newborn screening (NBS) for this disorder began in the United States around 2004. We compared visual outcomes among 40 participants with LCHADD or trifunctional protein deficiency diagnosed symptomatically to those who were diagnosed via NBS or a family history. Participants completed ophthalmologic testing including measures of visual acuity, electroretinograms (ERG), fundal imaging, contrast sensitivity, and visual fields. Records were reviewed to document medical and treatment history. Twelve participants presented symptomatically with hypoglycemia, failure to thrive, liver dysfunction, cardiac arrest, or rhabdomyolysis. Twenty eight were diagnosed by NBS or due to a family history of LCHADD. Participants diagnosed symptomatically were older but had similar percent males and genotypes as those diagnosed by NBS. Treatment consisted of fasting avoidance, dietary long-chain fat restriction, MCT, C7, and/or carnitine supplementation. Visual acuity, rod- and cone-driven amplitudes on ERG, contrast sensitivity scores, and visual fields were all significantly worse among participants diagnosed symptomatically compared to NBS. In mixed-effects models, both age and presentation (symptomatic vs. NBS) were significant independent factors associated with visual outcomes. This suggests that visual outcomes were improved by NBS, but there was still lower visual function with advancing age in both groups. Early diagnosis and treatment by NBS is associated with improved visual outcomes and retinal function compared to participants who presented symptomatically. Despite the impact of early intervention, chorioretinopathy was greater with advancing age, highlighting the need for novel treatments.
长链 3-羟酰基辅酶 A 脱氢酶（LCHADD）是唯一一种会发展为进行性脉络膜视网膜病变导致视力丧失的脂肪酸氧化障碍；这种疾病的新生儿筛查（NBS）于 2004 年左右开始在美国进行。我们比较了 40 名 LCHADD 或三功能蛋白缺乏症患者的视力结果，这些患者是通过症状诊断、NBS 诊断或家族史诊断的。参与者完成了眼科测试，包括视力、视网膜电图（ERG）、眼底成像、对比敏感度和视野测量。记录被审查以记录医疗和治疗史。有 12 名参与者表现出低血糖、生长不良、肝功能障碍、心脏骤停或横纹肌溶解等症状。28 名参与者是通过 NBS 或家族史诊断为 LCHADD 的。症状性诊断的参与者年龄较大，但男性比例和基因型与 NBS 诊断的参与者相似。治疗包括避免禁食、限制长链脂肪饮食、中链甘油三酯、C7 和/或肉碱补充。与 NBS 诊断的参与者相比，症状性诊断的参与者的视力、ERG 中的棒状和锥状驱动幅度、对比敏感度评分和视野都明显更差。在混合效应模型中，年龄和表现（症状性与 NBS）都是与视觉结果相关的独立显著因素。这表明 NBS 可以改善视觉结果，但在两组中，随着年龄的增长，视力仍然较差。与症状性表现的参与者相比，通过 NBS 进行早期诊断和治疗与改善的视觉结果和视网膜功能相关。尽管早期干预有影响，但随着年龄的增长，脉络膜视网膜病变变得更加严重，这突出了需要新的治疗方法。
