Department of Metabolic Diseases, Dutch Fatty Acid Oxidation Expertise Center, Wilhelmina Children's Hospital (UMCU), University Medical Center Utrecht, Internal Mail KE 04.306.0, PO Box 85090 3508 AB, Utrecht, Netherlands.
Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, Netherlands.
J Inherit Metab Dis. 2019 Jan;42(1):159-168. doi: 10.1002/jimd.12037.
Patients with very long chain acyl-CoA dehydrogenase deficiency (VLCADD), a long chain fatty acid oxidation disorder, are traditionally treated with a long chain triglyceride (LCT) restricted and medium chain triglyceride (MCT) supplemented diet. Introduction of VLCADD in newborn screening (NBS) programs has led to the identification of asymptomatic newborns with VLCADD, who may have a more attenuated phenotype and may not need dietary adjustments.
To define dietary strategies for individuals with VLCADD based on the predicted phenotype.
We evaluated long-term dietary histories of a cohort of individuals diagnosed with VLCADD identified before the introduction of VLCADD in NBS and their beta-oxidation (LC-FAO) flux score (rate of oleate oxidation) in cultured skin fibroblasts in relation to the clinical outcome. Based on these results a dietary strategy is proposed.
Sixteen individuals with VLCADD were included. One had an LC-FAO flux score >90%, was not on a restricted diet and is asymptomatic to date. Four patients had an LC-FAO flux score <10%, and significant VLCADD related symptoms despite the use of strict diets including LCT restriction, MCT supplementation and nocturnal gastric drip feeding. Patients with an LC-FAO flux score between 10 and 90% (n = 11) showed a more heterogeneous phenotype.
This study shows that a strict diet cannot prevent poor clinical outcome in severely affected patients and that the LC-FAO flux is a good predictor of clinical outcome in individuals with VLCADD identified before its introduction in NBS. Hereby, we propose an individualized dietary strategy based on the LC-FAO flux score.
患有极长链酰基辅酶 A 脱氢酶缺乏症（VLCADD）的患者为长链脂肪酸氧化障碍患者，传统上采用限制长链甘油三酯（LCT）和补充中链甘油三酯（MCT）的饮食进行治疗。VLCADD 纳入新生儿筛查（NBS）计划后，发现了无症状的 VLCADD 新生儿，他们可能具有更轻微的表型，可能不需要进行饮食调整。
根据预测表型确定 VLCADD 患者的饮食策略。
我们评估了在 NBS 中引入 VLCADD 之前诊断出的 VLCADD 患者队列的长期饮食史，以及他们培养的皮肤成纤维细胞中的β氧化（LC-FAO）通量评分（油酸氧化率）与临床结果的关系。基于这些结果提出了一种饮食策略。
纳入了 16 名 VLCADD 患者。其中 1 名患者的 LC-FAO 通量评分>90%，未接受限制饮食，且至今无症状。4 名患者的 LC-FAO 通量评分<10%，尽管采用了严格的饮食，包括限制 LCT、补充 MCT 和夜间胃滴注喂养，但仍有明显的 VLCADD 相关症状。LC-FAO 通量评分在 10%至 90%之间的患者（n=11）表现出更具异质性的表型。
本研究表明，严格的饮食不能预防严重影响患者的不良临床结局，并且 LC-FAO 通量是预测 NBS 前确诊的 VLCADD 患者临床结局的良好指标。因此，我们提出了一种基于 LC-FAO 通量评分的个体化饮食策略。
