PDF(Pubmed)
Abstract：
BACKGROUND: Transcobalamin II (TCN2) defect is a rare metabolic disorder associated with a range of neurological manifestations, including mild developmental delay, severe intellectual disability, ataxia, and, in some cases, seizures. Cobalamin, an essential nutrient, plays a crucial role in central nervous system myelination.
METHODS: We present a family with an index patient who exhibited progressive neurodevelopmental regression starting at 9 months of age, accompanied by myoclonic seizures, ataxia, and tremor. No significant hematological abnormalities were observed. Exome sequencing analysis identified a novel homozygous mutation, c.3G>A - P(Met1I), affecting the acceptor site of intron 4 of the TCN2 gene (chromosome 22: 31003321, NM_000355.4), leading to likely pathogenic variant potentially affecting translation. Following treatment with hydroxocobalamin, the patient demonstrated partial clinical improvement. He has a sibling with overt hematological abnormalities and subtle neurological abnormalities who is homozygous to the same mutation. Both parents are heterozygous for the same mutation.
CONCLUSIONS: In infants presenting with unexplained non-specific neurological symptoms, irrespective of classical signs of vitamin B12 deficiency, evaluation for TCN2 defect should be considered. Early diagnosis and appropriate management can lead to favorable outcomes.
METHODS: We present a family with an index patient who exhibited progressive neurodevelopmental regression starting at 9 months of age, accompanied by myoclonic seizures, ataxia, and tremor. No significant hematological abnormalities were observed. Exome sequencing analysis identified a novel homozygous mutation, c.3G>A - P(Met1I), affecting the acceptor site of intron 4 of the TCN2 gene (chromosome 22: 31003321, NM_000355.4), leading to likely pathogenic variant potentially affecting translation. Following treatment with hydroxocobalamin, the patient demonstrated partial clinical improvement. He has a sibling with overt hematological abnormalities and subtle neurological abnormalities who is homozygous to the same mutation. Both parents are heterozygous for the same mutation.
CONCLUSIONS: In infants presenting with unexplained non-specific neurological symptoms, irrespective of classical signs of vitamin B12 deficiency, evaluation for TCN2 defect should be considered. Early diagnosis and appropriate management can lead to favorable outcomes.
摘要：
背景：转钴胺II（TCN2）缺陷是一种与一系列神经系统表现相关的罕见代谢紊乱，包括轻度发育迟缓,严重的智力残疾，共济失调,and,在某些情况下,癫痫发作。钴胺,一种必需的营养素，在中枢神经系统髓鞘形成中起着至关重要的作用。
方法：我们介绍了一个有指数患者的家庭，该患者从9个月大开始表现出进行性神经发育消退，伴有肌阵挛性癫痫,共济失调,和震颤。未观察到明显的血液学异常。外显子组测序分析确定了一个新的纯合突变，c.3G>A-P(Met1I)，影响TCN2基因内含子4的受体位点(染色体22:31003321,NM_000355.4),导致可能的致病变异，可能影响翻译。用羟钴胺治疗后，患者表现出部分临床改善。他有一个兄弟姐妹，有明显的血液学异常和微妙的神经系统异常，是纯合的。两个亲本对于相同的突变是杂合的。
结论：在出现无法解释的非特异性神经症状的婴儿中，不管维生素B12缺乏的经典迹象，应考虑评估TCN2缺陷。早期诊断和适当的管理可以导致有利的结果。
方法：我们介绍了一个有指数患者的家庭，该患者从9个月大开始表现出进行性神经发育消退，伴有肌阵挛性癫痫,共济失调,和震颤。未观察到明显的血液学异常。外显子组测序分析确定了一个新的纯合突变，c.3G>A-P(Met1I)，影响TCN2基因内含子4的受体位点(染色体22:31003321,NM_000355.4),导致可能的致病变异，可能影响翻译。用羟钴胺治疗后，患者表现出部分临床改善。他有一个兄弟姐妹，有明显的血液学异常和微妙的神经系统异常，是纯合的。两个亲本对于相同的突变是杂合的。
结论：在出现无法解释的非特异性神经症状的婴儿中，不管维生素B12缺乏的经典迹象，应考虑评估TCN2缺陷。早期诊断和适当的管理可以导致有利的结果。
