Bourque Danielle K, Mellin-Sanchez Lizbeth E, Bullivant Garrett, Cruz Vivian, Feigenbaum Anette, Hewson Stacy, Raiman Julian, Schulze Andreas, Siriwardena Komudi, Mercimek-Andrews Saadet
Division of Clinical and Metabolic Genetics, Department of Pediatrics The Hospital for Sick Children Toronto Ontario Canada.
Department of Pediatrics University of Toronto Toronto Ontario Canada.
JIMD Rep. 2020 Nov 8;57(1):102-114. doi: 10.1002/jmd2.12179. eCollection 2021 Jan.
Biallelic variants in results in the combined methylmalonic aciduria and homocystinuria, called cobalamin (cbl) C (cblC) deficiency. We report 26 patients with cblC deficiency with their phenotypes, genotypes, biochemical parameters, and treatment outcomes, who were diagnosed and treated at our center. We divided all cblC patients into two groups: group 1: SX group: identified after manifestations of symptoms (n = 11) and group 2: NB group: identified during the asymptomatic period via newborn screening (NBS) or positive family history of cblC deficiency (n = 15). All patients in the SX group had global developmental delay and/or cognitive dysfunction at the time of the diagnosis and at the last assessment. Seizure, stroke, retinopathy, anemia, cerebral atrophy, and thin corpus callosum in brain magnetic resonance imaging (MRI) were common in patients in the SX group. Global developmental delay and cognitive dysfunction was present in nine patients in the NB group at the last assessment. Retinopathy, anemia, and cerebral atrophy and thin corpus callosum in brain MRI were less frequent. We report favorable outcomes in patients identified in the neonatal period and treated pre-symptomatically. Identification of cblC deficiency by NBS is crucial to improve neurodevelopmental outcomes.
双等位基因变异会导致合并甲基丙二酸尿症和高胱氨酸尿症，即钴胺素（cbl）C（cblC）缺乏症。我们报告了26例在本中心诊断和治疗的cblC缺乏症患者，包括他们的表型、基因型、生化参数和治疗结果。我们将所有cblC患者分为两组：第1组：症状出现后确诊组（SX组）：11例；第2组：无症状期确诊组（NB组）：通过新生儿筛查（NBS）或cblC缺乏症家族史阳性在无症状期确诊，共15例。SX组所有患者在诊断时和最后一次评估时均有全面发育迟缓及/或认知功能障碍。SX组患者常见癫痫、中风、视网膜病变、贫血、脑萎缩以及脑磁共振成像（MRI）显示胼胝体变薄。在最后一次评估时，NB组有9例患者存在全面发育迟缓和认知功能障碍。视网膜病变、贫血以及脑MRI显示脑萎缩和胼胝体变薄的情况较少见。我们报告了新生儿期确诊并在症状出现前接受治疗的患者取得了良好的治疗效果。通过NBS识别cblC缺乏症对于改善神经发育结局至关重要。
