核黄素反应性多种酰基辅酶A脱氢酶缺乏症患者的高同型半胱氨酸血症

Hyperhomocysteinemia in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.

作者信息

Zhang Huiqiu, Zhao Rongjuan, Ma Jing, Zhang Jingfei, Wang Juan, Chang Xueli, Guo Junhong, Zhang Wei

机构信息

Department of Neurology, First Hospital, Shanxi Medical University, Taiyuan, China.

First Clinical Medical College, Shanxi Medical University, Taiyuan, China.

出版信息

Muscle Nerve. 2023 Nov;68(5):750-757. doi: 10.1002/mus.27960. Epub 2023 Aug 22.

DOI:10.1002/mus.27960

PMID:37606529

Abstract

INTRODUCTION/AIMS: Riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) is an autosomal recessive disease chiefly caused by variants of ETFDH affecting fatty acid metabolism. In our cohort, hyperhomocysteinemia (HHcy) was common. In this study we aimed to identify the association between RR-MADD and HHcy.

METHODS

We performed a retrospective review of 13 patients with RR-MADD. Thirty-three healthy controls were recruited, and logistic regression was used to investigate the association between RR-MADD and HHcy. Muscle tissues from six patients and six controls without myopathies were collected to measure the levels of flavin adenine dinucleotide (FAD), an active form of riboflavin. Whole-exome sequencing was performed to identify the disease-associated variants.

RESULTS

The RR-MADD patients had a higher prevalence of HHcy (9 of 12) than controls (6 of 33, P < .001). In the multivariate analysis, RR-MADD was positively related to HHcy (P = .014). Muscular FAD levels were decreased in RR-MADD patients (P = .006). Thirteen variants (8 reported and 5 novel) were identified in ETFDH. Of these, c.250G > A was the most common pathogenic variant with an allelic frequency of 4 of 20.

DISCUSSION

HHcy was associated with RR-MADD and may aid in the diagnosis of the disease. Our findings expand the mutational spectrum of RR-MADD.

摘要

引言/目的：核黄素反应性多种酰基辅酶A脱氢酶缺乏症（RR-MADD）是一种常染色体隐性疾病，主要由影响脂肪酸代谢的ETFDH变异引起。在我们的队列中，高同型半胱氨酸血症（HHcy）很常见。在本研究中，我们旨在确定RR-MADD与HHcy之间的关联。

方法

我们对13例RR-MADD患者进行了回顾性研究。招募了33名健康对照，采用逻辑回归分析RR-MADD与HHcy之间的关联。收集了6例患者和6例无肌病对照的肌肉组织，以测量核黄素的活性形式黄素腺嘌呤二核苷酸（FAD）的水平。进行全外显子组测序以鉴定与疾病相关的变异。

结果

RR-MADD患者中HHcy的患病率（12例中的9例）高于对照组（33例中的6例，P < .001）。在多变量分析中，RR-MADD与HHcy呈正相关（P = .014）。RR-MADD患者的肌肉FAD水平降低（P = .006）。在ETFDH中鉴定出13个变异（8个已报道的和5个新的）。其中，c.250G > A是最常见的致病变异，等位基因频率为20个中的4个。