Abstract：
OBJECTIVE: Transcobalamin II (TC) promotes the cellular uptake of cobalamin (Cbl) through receptor-mediated endocytosis of the TC-cbl complex in peripheral tissues. TC deficiency is a rare disorder that causes intracellular Cbl depletion. It presents in early infancy with a failure to thrive, diarrhea, anemia, agammaglobulinemia, and pancytopenia. Data from five TC-deficient patients including clinical, biochemical, and molecular findings, as well as long-term outcomes, were collected.
METHODS: Mutation analysis revealed one unreported pathogenic variant in the TCN2 gene. One patient had exocrine pancreatic insufficiency. We conducted a retrospective analysis of C3 and C3/C2 from dried blood samples, as this is implemented for newborn screening (NBS). We detected a marked increase in the C3/C2 ratio in two samples. Treatment was based on parenteral Cbl. Three patients treated before six months of age had an initial favorable outcome, whereas the two treated later or inadequately had neurological impairment.
CONCLUSIONS: This is the first report of Argentinean patients with TC deficiency that detected a new variant in TCN2. NBS may be a tool for the early detection of TC deficiency. This data emphasizes that TC deficiency is a severe disorder that requires early detection and long-term, aggressive therapy. Accurate diagnosis is imperative, because early detection and treatment can be life-saving.
METHODS: Mutation analysis revealed one unreported pathogenic variant in the TCN2 gene. One patient had exocrine pancreatic insufficiency. We conducted a retrospective analysis of C3 and C3/C2 from dried blood samples, as this is implemented for newborn screening (NBS). We detected a marked increase in the C3/C2 ratio in two samples. Treatment was based on parenteral Cbl. Three patients treated before six months of age had an initial favorable outcome, whereas the two treated later or inadequately had neurological impairment.
CONCLUSIONS: This is the first report of Argentinean patients with TC deficiency that detected a new variant in TCN2. NBS may be a tool for the early detection of TC deficiency. This data emphasizes that TC deficiency is a severe disorder that requires early detection and long-term, aggressive therapy. Accurate diagnosis is imperative, because early detection and treatment can be life-saving.
摘要：
目的：转钴胺素II（TC）通过受体介导的外周组织中TC-cbl复合物的内吞作用促进细胞对钴胺素（Cbl）的摄取。TC缺乏是引起细胞内Cbl耗竭的罕见病症。它在婴儿期早期表现出未能茁壮成长，腹泻,贫血,丙种球蛋白血症，和全血细胞减少症.来自五名TC缺乏患者的数据，包括临床，生物化学，和分子发现，以及长期结果，被收集。
方法：突变分析显示TCN2基因中有一个未报道的致病变异。一名患者有胰腺外分泌功能不全。我们对干血样本中的C3和C2/C3进行了回顾性分析，因为这是为新生儿筛查（NBS）实施的。我们在两个样品中检测到C3/C2比率的显著增加。治疗基于肠胃外Cbl。在六个月之前接受治疗的三名患者最初获得了良好的结果，而治疗较晚或治疗不充分的两人有神经功能缺损。
结论：这是阿根廷TC缺乏症患者在TCN2中检测到一种新的变异的第一份报告。NBS可能是早期发现TC缺乏症的工具。这些数据强调，TC缺乏症是一种严重的疾病，需要早期发现和长期治疗，积极的治疗。准确的诊断势在必行,因为早期发现和治疗可以挽救生命。
方法：突变分析显示TCN2基因中有一个未报道的致病变异。一名患者有胰腺外分泌功能不全。我们对干血样本中的C3和C2/C3进行了回顾性分析，因为这是为新生儿筛查（NBS）实施的。我们在两个样品中检测到C3/C2比率的显著增加。治疗基于肠胃外Cbl。在六个月之前接受治疗的三名患者最初获得了良好的结果，而治疗较晚或治疗不充分的两人有神经功能缺损。
结论：这是阿根廷TC缺乏症患者在TCN2中检测到一种新的变异的第一份报告。NBS可能是早期发现TC缺乏症的工具。这些数据强调，TC缺乏症是一种严重的疾病，需要早期发现和长期治疗，积极的治疗。准确的诊断势在必行,因为早期发现和治疗可以挽救生命。
