Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Center for Individualized Medicine, Mayo Clinic, Rochester, USA; Department of Clinical Genomics, Mayo Clinic, Rochester, USA.
Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Mol Genet Metab. 2019 Jan;126(1):6-13. doi: 10.1016/j.ymgme.2018.12.005. Epub 2018 Dec 11.
Menkes disease is a rare X-linked neurodegenerative disorder caused by defect in copper metabolism. Parenteral copper supplementation has been used as a potential disease-modifying treatment of Menkes disease for decades. However, recent evidence suggests its efficacy only when treatment is started within days after birth, which also has important implications related to the techniques that enable early diagnosis. We aim at proposing a guideline for prenatal and neonatal diagnosis and for disease-modifying treatment of Menkes disease, guided by a systematic review of the literature, and built in conjunction with medical experts, methodologists and patient representatives. Thirteen articles were used for our recommendations that were based on GRADE system. Reviewed evidence suggests that prenatal genetic diagnosis in families with previous diagnosis of Menkes disease is feasible; analysis of plasma catecholamine levels is accurate for neonatal diagnosis of Menkes disease; treatment with copper-histidine is effective to increase survival and reduce neurologic burden of the disease if initiated in the neonatal period; and, treatment indication should not be guided by patient's genotype. In conclusion, our guideline can contribute to standardize some aspects of the clinical care of patients with Menkes disease, especially reducing disease burden and mortality and providers' and families' anxiety.
Menkes 病是一种罕见的 X 连锁神经退行性疾病，由铜代谢缺陷引起。几十年来，肠外补充铜一直被用作 Menkes 病潜在的疾病修正治疗方法。然而，最近的证据表明，其疗效仅在出生后几天内开始治疗时才有效，这也与能够早期诊断的技术有关。我们旨在通过对文献的系统回顾，并结合医学专家、方法学家和患者代表，为 Menkes 病的产前和新生儿诊断以及疾病修正治疗提出指南。我们的建议基于 GRADE 系统，使用了 13 篇文章。综述证据表明，在有 Menkes 病既往诊断的家庭中进行产前基因诊断是可行的；血浆儿茶酚胺水平分析可准确诊断新生儿期的 Menkes 病；如果在新生儿期开始使用铜-组氨酸治疗，可有效提高生存率并减轻疾病的神经负担；并且，治疗指征不应根据患者的基因型来指导。总之，我们的指南有助于规范 Menkes 病患者的临床护理的某些方面，特别是降低疾病负担和死亡率，减轻提供者和家庭的焦虑。
