Nashabat Marwan, Maegawa Gustavo, Nissen Peter H, Nexo Ebba, Al-Shamrani Hussain, Al-Owain Mohammed, Alfadhel Majid
*Department of Pediatrics, King Abdullah International Medical Research Centre, Genetics Division #King Saud bin Abdulaziz University for Health Science, King Abdulaziz Medical City §Department of Pediatrics ∥Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre ¶Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia †Department of Pediatrics, Genetics & Metabolism, University of Florida, Gainesville, FL ‡Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
J Pediatr Hematol Oncol. 2017 Nov;39(8):e430-e436. doi: 10.1097/MPH.0000000000000857.
Cobalamin (vitamin B12 [Cbl]) is an essential cofactor for many biochemical pathways. Transcobalamin (TC) is required to internalize Cbl into the cells through membrane receptor-mediated endocytosis. Cbl is then processed in the cytoplasm and mitochondria by complementation factors leading to its active metabolites; methylcobalamin and 5-deoxyadenosyl-cobalamin. Deficiency of TC results in an elevation in methylmalonic acid and homocysteine. Patients usually present with macrocytic anemia, pancytopenia, failure to thrive, gastrointestinal symptoms, and neurological dysfunction. In this study, we report 4 patients from 2 unrelated families, with confirmed diagnosis of TC deficiency. Patients initially had a typical presentation of TC deficiency: severe diarrhea and vomiting, recurrent infections, stomatitis, macrocytic anemia, and neutropenia. Interestingly one of the patients was diagnosed at 3 months of age and developed ataxic gait related to cerebellar atrophy at the age of 14 months. His elder affected sibling was diagnosed at 5 months of age was completely normal. Two sibs, diagnosed at 2 months of age and immediately after birth, had autism spectrum disorder. Molecular investigations showed 2 novel mutations in TCN2 gene. Patients were treated and stayed stable on weekly injection of Cbl. In conclusion, TC deficiency has a wide heterogeneity in clinical phenotype, genotype, laboratory, and radiologic findings. Early detection of the disease and early initiation of aggressive parenteral treatment is probably associated with better prognosis and disease control.
钴胺素（维生素B12 [Cbl]）是许多生化途径所必需的辅助因子。转钴胺素（TC）是将Cbl通过膜受体介导的内吞作用内化到细胞中所必需的。然后，Cbl在细胞质和线粒体中由互补因子进行加工，生成其活性代谢产物；甲钴胺和5'-脱氧腺苷钴胺。TC缺乏会导致甲基丙二酸和同型半胱氨酸升高。患者通常表现为大细胞性贫血、全血细胞减少、生长发育不良、胃肠道症状和神经功能障碍。在本研究中，我们报告了来自2个无亲缘关系家庭的4例确诊为TC缺乏的患者。患者最初有典型的TC缺乏表现：严重腹泻和呕吐、反复感染、口腔炎、大细胞性贫血和中性粒细胞减少。有趣的是，其中1例患者在3个月大时被诊断出，14个月大时出现与小脑萎缩相关的共济失调步态。他年长的患病同胞在5个月大时被诊断出，当时完全正常。另外2例分别在2个月大时和出生后立即被诊断出的同胞患有自闭症谱系障碍。分子研究显示TCN2基因有2个新突变。患者接受了治疗，并通过每周注射Cbl保持稳定。总之，TC缺乏在临床表型、基因型、实验室检查和影像学表现方面具有广泛的异质性。疾病的早期发现和积极的肠外治疗的早期启动可能与更好的预后和疾病控制相关。
