Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
BMJ Case Rep. 2024 Oct 1;17(10):e259792. doi: 10.1136/bcr-2024-259792.
Menkes disease is a multisystem disorder caused by disturbances in copper absorption and metabolism. This lethal neurodegenerative disease presents with fine, 'kinky' hair, connective tissue dysfunction and developmental regression after 2-3 months of age. The primary variant associated with Menkes is in the gene with X-linked recessive inheritance. Historically, the diagnosis of Menkes has relied on clinical signs and symptoms, but as the disease has varying levels of severity and presentation, it can take months to diagnose and treat. Emerging technology for ultrarapid genome sequencing offers a DNA-based route of diagnosis with preliminary results in hours, allowing for earlier discovery and treatment of Menkes with the potential for better long-term outcomes. Ultrarapid whole genome sequencing identified a novel, likely pathogenic, frameshift variant in the gene consistent with a diagnosis of Menkes disease. The clinical manifestations and pathophysiology of this disorder, as well as a rapid DNA-based diagnosis, are described in this case.
Menkes 病是一种多系统紊乱症，由铜吸收和代谢紊乱引起。这种致命的神经退行性疾病在 2-3 个月后出现细小、“卷曲”的头发、结缔组织功能障碍和发育倒退。与 Menkes 相关的主要变异是在 X 连锁隐性遗传的 基因中。从历史上看，Menkes 的诊断依赖于临床症状和体征，但由于该疾病的严重程度和表现程度不同，可能需要数月时间才能诊断和治疗。超快速基因组测序的新兴技术提供了一种基于 DNA 的诊断途径，初步结果可在数小时内获得，从而更早地发现和治疗 Menkes，有可能获得更好的长期结果。超快速全基因组测序在 基因中发现了一个新的、可能致病的移码变异，与 Menkes 病的诊断一致。本文描述了该疾病的临床表现、病理生理学以及快速的基于 DNA 的诊断。
