目的 对1例Menkes患儿及其家系的临床特征及ATP7A基因变异进行分析，明确其致病原因，为临床诊断提供依据。 方法 选择2022年3月在四川大学华西第二医院确诊的1例Menkes患儿及其家系作为研究对象，分析其临床表现、实验室检查及ATP7A基因变异检测的结果。 结果 患儿主要表现为癫痫发作、全面发育落后，特殊面容、毛发稀疏、卷曲、乳酸、丙酮酸增高，铜兰蛋白明显降低；脑电图示多灶性尖、棘、多棘(慢)、多形性慢波频繁发放；头颅磁共振成像可见多发迂曲走行的血管影。全外显子组测序显示其ATP7A基因存在c.3076delA(p.Ile1026*)半合子变异，该变异遗传自母亲，可导致蛋白质翻译提前终止。根据美国医学遗传学与基因组学学会(ACMG)相关指南判定为致病变异(PVS1+PM2+PP4)。 结论 ATP7A基因c.3076del系新发变异，可能是本研究患儿的致病原因。基因检测为患儿的临床诊断提供了依据，并进一步丰富了ATP7A基因的变异谱。Menkes病患者的乳酸及丙酮酸水平显著升高，可用于指导诊断和管理。携带者的头发在显微镜下与患者相似，可能有助于诊断。 Objective To explore the clinical characteristics and variants of ATP7A gene in a child with Menkes disease. Methods A child with Menkes disease diagnosed at the West China Second Hospital of Sichuan University and its family members in March 2022 was selected as the study subjects. Clinical manifestations and results of laboratory tests and genetic testing were summarized. Results The main manifestations of the child included seizures, global development delay, facial dysmorphism, sparse and curly hair, increased lactate and pyruvate, and significantly decreased cuprin. EEG showed frequent issuance of multifocal spikes, spines, polyspines (slow) and polymorphic slow waves. Multiple tortuous vascular shadows were observed on cranial MRI. Whole exome sequencing revealed that the child has harbored a hemizygous c. 3076delA (p.ile1026*) variant of the ATP7A gene, which was inherited from his mother. The variant may lead to premature termination of protein translation. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as pathogenic (PVS1+ PM2+ PP4). Conclusion The c. 3076delA (p.Ile1026*) variant of the ATP7A gene probably underlay the Menkes disease in this child. Above finding has provided evidence for clinical diagnosis. The significantly increased lactic acid and pyruvate can be used as a reference for the diagnosis and management of Menkes disease. Microscopic abnormalities in the hair of the carriers may also facilitate their diagnosis.
Abstract
Objective To explore the clinical characteristics and variants of ATP7A gene in a child with Menkes disease. Methods A child with Menkes disease diagnosed at the West China Second Hospital of Sichuan University and its family members in March 2022 was selected as the study subjects. Clinical manifestations and results of laboratory tests and genetic testing were summarized. Results The main manifestations of the child included seizures, global development delay, facial dysmorphism, sparse and curly hair, increased lactate and pyruvate, and significantly decreased cuprin. EEG showed frequent issuance of multifocal spikes, spines, polyspines (slow) and polymorphic slow waves. Multiple tortuous vascular shadows were observed on cranial MRI. Whole exome sequencing revealed that the child has harbored a hemizygous c. 3076delA (p.ile1026*) variant of the ATP7A gene, which was inherited from his mother. The variant may lead to premature termination of protein translation. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as pathogenic (PVS1+ PM2+ PP4). Conclusion The c. 3076delA (p.Ile1026*) variant of the ATP7A gene probably underlay the Menkes disease in this child. Above finding has provided evidence for clinical diagnosis. The significantly increased lactic acid and pyruvate can be used as a reference for the diagnosis and management of Menkes disease. Microscopic abnormalities in the hair of the carriers may also facilitate their diagnosis.
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