Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands
Department of Pediatrics, Division of Metabolic Disorders, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.
J Med Genet. 2023 Nov 27;60(12):1177-1185. doi: 10.1136/jmg-2023-109206.
Newborn screening (NBS) programmes identify a wide range of disease phenotypes, which raises the question whether early identification and treatment is beneficial for all. This study aims to answer this question for primary carnitine deficiency (PCD) taking into account that NBS for PCD identifies newborns with PCD and also until then undiagnosed mothers.
We investigated clinical, genetic (variants in gene) and functional (carnitine transport activity in fibroblasts) characteristics of all referred individuals through NBS (newborns and mothers) and clinically diagnosed patients with PCD (not through NBS). Disease phenotype in newborns was predicted using data from PCD mothers and cases published in literature with identical variants.
PCD was confirmed in 19/131 referred newborns, 37/82 referred mothers and 5 clinically diagnosed patients. Severe symptoms were observed in all clinically diagnosed patients, 1 newborn and none of the mothers identified by NBS. PCD was classified as severe in all 5 clinically diagnosed patients, 3/19 newborns and 1/37 mothers; as benign in 8/19 newborns and 36/37 mothers and as unknown in 8/19 newborns. Carnitine transport activity completely separated severe phenotype from benign phenotype (median (range): 4.0% (3.5-5.0)] vs 26% (9.5-42.5), respectively).
The majority of mothers and a significant proportion of newborns with PCD identified through NBS are likely to remain asymptomatic without early treatment. Conversely, a small proportion of newborns with predicted severe PCD could greatly benefit from early treatment. Genetic variants and carnitine transport activity can be used to distinguish between these groups.
新生儿筛查（NBS）项目可识别出广泛的疾病表型，这就提出了一个问题，即早期识别和治疗是否对所有患者都有益。本研究旨在考虑到 NBS 可识别出患有原发性肉碱缺乏症（PCD）的新生儿和之前未被诊断的母亲，回答这一问题。
我们通过 NBS（新生儿和母亲）和临床诊断为 PCD 的患者（非通过 NBS）调查了所有被转诊的个体的临床、遗传（基因中的变体）和功能（成纤维细胞中的肉碱转运活性）特征。通过来自 PCD 母亲和文献中具有相同变体的病例的数据预测新生儿的疾病表型。
在 131 名被转诊的新生儿中，82 名被转诊的母亲和 5 名临床诊断的 PCD 患者中确认了 PCD。所有临床诊断的患者、1 名新生儿和通过 NBS 识别的母亲均观察到严重症状。在所有 5 名临床诊断的患者、19 名新生儿中的 3 名和 37 名母亲中的 1 名中，PCD 被归类为严重；在 8 名新生儿和 36 名母亲中被归类为良性；在 8 名新生儿中被归类为未知。肉碱转运活性完全将严重表型与良性表型分开（中位数（范围）：分别为 4.0%（3.5-5.0）和 26%（9.5-42.5））。
通过 NBS 识别的大多数 PCD 母亲和新生儿可能会保持无症状，无需早期治疗。相反，一小部分预测为严重 PCD 的新生儿可能会从早期治疗中获益匪浅。遗传变异和肉碱转运活性可用于区分这些群体。
