Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of Nancy, University of Lorraine, INSERM UMR_S 1256, 54000 Nancy, France; Department of Pediatrics, University Hospital of Nancy, 54000 Nancy, France; Reference Center for Inborn Errors of Metabolism (ORPHA67872), University Hospital of Nancy, 54000 Nancy, France.
Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of Nancy, University of Lorraine, INSERM UMR_S 1256, 54000 Nancy, France; Reference Center for Inborn Errors of Metabolism (ORPHA67872), University Hospital of Nancy, 54000 Nancy, France; Department of Molecular Medicine, Division of Biochemistry, Molecular Biology, Nutrition, and Metabolism, University Hospital of Nancy, 54000 Nancy, France.
Cell Rep Med. 2022 Jul 19;3(7):100670. doi: 10.1016/j.xcrm.2022.100670. Epub 2022 Jun 27.
Inherited disorders of B metabolism produce a broad spectrum of manifestations, with limited knowledge of the influence of age and the function of related genes. We report a meta-analysis on 824 patients with a genetically proven diagnosis of an inherited disorder of vitamin B metabolism. Gene clusters and age categories are associated with patients' manifestations. The "cytoplasmic transport" cluster is associated with neurological and ophthalmological manifestations, the "mitochondrion" cluster with hypotonia, acute metabolic decompensation, and death, and the "B availability" and "remethylation" clusters with anemia and cytopenia. Hypotonia, EEG abnormalities, nystagmus, and strabismus are predominant in the younger patients, while neurological manifestations, such as walking difficulties, peripheral neuropathy, pyramidal syndrome, cerebral atrophy, psychiatric disorders, and thromboembolic manifestations, are predominant in the older patients. These results should prompt systematic checking of markers of vitamin B status, including homocysteine and methylmalonic acid, when usual causes of these manifestations are discarded in adult patients.
遗传性 B 族代谢紊乱会产生广泛的临床表现，但对年龄和相关基因功能的影响了解有限。我们对 824 名遗传性 B 族代谢紊乱患者进行了一项荟萃分析，这些患者的诊断均通过基因检测证实。基因簇和年龄类别与患者的临床表现相关。“胞质转运”簇与神经和眼科表现相关，“线粒体”簇与肌张力减退、急性代谢失代偿和死亡相关，而“B 族可用性”和“再甲基化”簇与贫血和血细胞减少相关。肌张力减退、脑电图异常、眼球震颤和斜视在年轻患者中更为常见，而神经表现，如行走困难、周围神经病、锥体束征、脑萎缩、精神障碍和血栓栓塞表现，则在老年患者中更为常见。这些结果提示，当成年患者出现这些表现的常见原因被排除时，应系统检查维生素 B 状态的标志物，包括同型半胱氨酸和甲基丙二酸。
