Trakadis Y J, Alfares A, Bodamer O A, Buyukavci M, Christodoulou J, Connor P, Glamuzina E, Gonzalez-Fernandez F, Bibi H, Echenne B, Manoli I, Mitchell J, Nordwall M, Prasad C, Scaglia F, Schiff M, Schrewe B, Touati G, Tchan M C, Varet B, Venditti C P, Zafeiriou D, Rupar C A, Rosenblatt D S, Watkins D, Braverman N
Department of Medical Genetics, McGill University Health Centre, Montreal, QC, Canada,
J Inherit Metab Dis. 2014 May;37(3):461-73. doi: 10.1007/s10545-013-9664-5. Epub 2013 Dec 5.
Transcobalamin (TC) transports cobalamin from blood into cells. TC deficiency is a rare autosomal recessive disorder usually presenting in early infancy with failure to thrive, weakness, diarrhoea, pallor, anemia, and pancytopenia or agammaglobulinemia. It can sometimes resemble neonatal leukemia or severe combined immunodeficiency disease. Diagnosis of TC deficiency is suspected based on megaloblastic anemia, elevation of total plasma homocysteine, and blood or urine methylmalonic acid. It is confirmed by studying the synthesis of TC in cultured fibroblasts, or by molecular analysis of the TCN2 gene. TC deficiency is treatable with supplemental cobalamin, but the optimal type, route and frequency of cobalamin administration and long term patient outcomes are unknown. Here we present a series of 30 patients with TC deficiency, including an update on multiple previously published patients, in order to evaluate the different treatment strategies and provide information about long term outcome. Based on the data presented, current practice appears to favour treatment of individuals with TC deficiency by intramuscular injections of hydroxy- or cyanocobalamin. In most cases presented, at least weekly injections (1 mg IM) were necessary to ensure optimal treatment. Most centres adjusted the treatment regimen based on monitoring CBC, total plasma homocysteine, plasma and urine methylmalonic acid, as well as, clinical status. Finally, continuing IM treatment into adulthood appears to be beneficial.
转钴胺素（TC）将钴胺素从血液转运至细胞内。TC缺乏是一种罕见的常染色体隐性疾病，通常在婴儿早期出现，表现为发育不良、虚弱、腹泻、面色苍白、贫血、全血细胞减少或无丙种球蛋白血症。它有时可能类似于新生儿白血病或严重联合免疫缺陷病。基于巨幼细胞贫血、血浆总同型半胱氨酸升高以及血液或尿液甲基丙二酸水平，怀疑存在TC缺乏。通过研究培养的成纤维细胞中TC的合成，或对TCN2基因进行分子分析来确诊。TC缺乏可用补充钴胺素进行治疗，但钴胺素给药的最佳类型、途径和频率以及患者的长期预后尚不清楚。在此，我们报告了30例TC缺乏患者的系列病例，包括对之前多篇发表病例的更新，以评估不同的治疗策略并提供长期预后信息。根据所呈现的数据，目前的做法似乎倾向于通过肌肉注射羟基钴胺素或氰钴胺素治疗TC缺乏患者。在大多数呈现的病例中，至少每周注射（1毫克肌肉注射）是确保最佳治疗所必需的。大多数中心根据监测全血细胞计数、血浆总同型半胱氨酸、血浆和尿液甲基丙二酸以及临床状况来调整治疗方案。最后，持续进行肌肉注射治疗直至成年似乎是有益的。
