Division of Genetics and Metabolism, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
M Health Fairview, Minneapolis, Minnesota, USA.
Am J Med Genet A. 2021 Jun;185(6):1870-1874. doi: 10.1002/ajmg.a.62170. Epub 2021 Mar 17.
Cobalamin J disease (CblJ) is an ultra-rare autosomal recessive disorder of intracellular cobalamin metabolism associated with combined methylmalonic acidemia and homocystinuria. It is caused by pathogenic variants in ABCD4, which encodes an ATP-binding cassette (ABC) transporter that affects the lysosomal release of cobalamin (Cbl) into the cytoplasm. Only six cases of CblJ have been reported in the literature. Described clinical features include feeding difficulties, failure to thrive, hypotonia, seizures, developmental delay, and hematological abnormalities. Information on clinical outcomes is extremely limited, and no cases of presymptomatic diagnosis have been reported. We describe a now 17-month-old male with CblJ detected by newborn screening and confirmed by biochemical, molecular, and complementation studies. With early detection and initiation of treatment, this patient has remained asymptomatic with normal growth parameters and neurodevelopmental function. To the best of our knowledge, this report represents the first asymptomatic and neurotypical patient with CblJ.
钴胺素 J 病(CblJ)是一种罕见的常染色体隐性遗传疾病,涉及细胞内钴胺素代谢,伴有甲基丙二酸血症和同型胱氨酸尿症。它是由 ABCD4 中的致病性变异引起的,该基因编码一种影响钴胺素(Cbl)向细胞质溶酶体释放的三磷酸腺苷结合盒(ABC)转运蛋白。文献中仅报道了 6 例 CblJ。描述的临床特征包括喂养困难、生长不良、张力减退、癫痫发作、发育迟缓以及血液学异常。有关临床结局的信息极其有限,也没有报道过无症状诊断的病例。我们描述了一位 17 个月大的男性,他在新生儿筛查中被检测出 CblJ,并通过生化、分子和互补研究得到证实。通过早期发现和治疗,该患者一直无症状,生长参数和神经发育功能正常。据我们所知,这是首例无症状和神经典型的 CblJ 患者报告。