J.M. Zhang , L.L. Hao , W.J. Qiu , H.W. Zhang , T. Chen , W.J. Ji , Y. Zhang , F. Liu , X.F. Gu , S.H. Yang , L.S. Han
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引用次数: 0
摘要
背景:丙二酰-CoA脱羧酶(MLYCD)缺乏症又称丙二酸尿症(MAD),是一种罕见的常染色体隐性遗传代谢缺陷。本研究旨在调查五名丙二酸尿症患者的临床和分子特征,以提高临床医生对该病的认识:方法:采用桑格测序法检测先天性患者及其父母的 MLYCD 变异并进行遗传分析:五名MAD患者(5个月至9.6岁,两男三女)很少出现代谢失调或癫痫发作。所有患者均表现出不同程度的发育迟缓和肌张力低下。我们的研究扩大了 MLYCD 基因变异的范围。在所有五名患者中均检测到了 MLYCD 基因变异,并确定了五个新的变异:c.60delG (p.Arg21Glyfs*52), c.928C > T (p.Arg310*), c.1293G > T (p.Trp431Cys), c.721T > C (p.Ser241Pro), 以及外显子 4-5 缺失。此外,各种基因型与表型之间没有相关性:结论:高中链甘油三酯和低长链甘油三酯饮食辅以左旋肉碱对大多数患者有效,可改善心肌病和肌肉无力。新生儿筛查有助于这种罕见疾病的早期诊断、治疗和预后。
Clinical, biochemical and genetic characteristics and long-term follow-up of five patients with malonyl-CoA decarboxylase deficiency
Background
Malonyl-CoA decarboxylase (MLYCD) deficiency, also known as malonic aciduria (MAD), is a rare autosomal recessive inherited metabolic defect. In this study, we aimed to investigate the clinical and molecular features of five patients with MAD in order to increase clinicians’ awareness of the disease.
Methods
Sanger sequencing was used to detect and genetically analyze the MLYCD variations in the preexisting patients and their parents.
Results
Five patients with MAD (5 months to 9.6 years old; two males and three females) rarely exhibited metabolic decompensation episodes or seizures. All patients exhibited varying degrees of developmental delay and hypotonia. Our study expands the spectrum of variants of the MLYCD gene. MLYCD gene variations were detected in all five patients, and five new variants were identified: c.60delG (p.Arg21Glyfs*52), c.928C > T (p.Arg310*), c.1293G > T (p.Trp431Cys), c.721T > C (p.Ser241Pro), and Exons 4–5 deletion. Additionally, there is no correlation between various genotypes and phenotypes.
Conclusion
A high-medium-chain triglyceride and low-long-chain triglyceride diet supplemented with L-carnitine was effective in most patients and may improve cardiomyopathy and muscle weakness. Newborn screening may aid in the early diagnosis, treatment, and prognosis of this rare disorder.
期刊介绍:
Brain and Development (ISSN 0387-7604) is the Official Journal of the Japanese Society of Child Neurology, and is aimed to promote clinical child neurology and developmental neuroscience.
The journal is devoted to publishing Review Articles, Full Length Original Papers, Case Reports and Letters to the Editor in the field of Child Neurology and related sciences. Proceedings of meetings, and professional announcements will be published at the Editor''s discretion. Letters concerning articles published in Brain and Development and other relevant issues are also welcome.