Weisfeld-Adams James D, McCourt Emily A, Diaz George A, Oliver Scott C
Children's Hospital Colorado, Aurora, CO, USA; Division of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Children's Hospital Colorado, Aurora, CO, USA; Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, USA.
Mol Genet Metab. 2015 Apr;114(4):537-46. doi: 10.1016/j.ymgme.2015.01.012. Epub 2015 Feb 19.
The association between combined methylmalonic acidemia and homocystinuria of cblC type (cobalamin C defect, cblC) and ocular disease is now well recognized, and is a significant component of morbidity and disability associated with the condition. In this review, through collation of historically reported cases of early- and late-onset cblC and previously unreported cases, we have attempted to characterize the epidemiology, clinical features, and pathomechanisms of individual ocular features of cblC. These data suggest that maculopathy and nystagmus with abnormal vision are extremely common and affect the majority of children with early-onset cblC, usually before school age; strabismus and optic atrophy are also seen at relatively high frequency. The timing of progression of macular disease may coincide with a critical period of postnatal foveal development. Maculopathy and retinal disease may be subclinical and show only partial correlation with the extent of visual deficits, and visual deterioration may be relentlessly progressive in spite of aggressive treatment of biochemical abnormalities. In later-onset forms of the disease, visual loss and ocular complications appear to be infrequent. Finally, we discuss investigational strategies in diagnosing and characterizing eye disease in individuals with cblC, explore possible therapeutic avenues that may attenuate progression and severity of eye disease, and propose a clinical surveillance guideline for monitoring progression of ocular disease in children and adults with cblC.
钴胺素C型（钴胺素C缺陷，cblC）合并甲基丙二酸血症和高胱氨酸尿症与眼部疾病之间的关联现已得到充分认识，并且是与该病症相关的发病和残疾的重要组成部分。在本综述中，通过整理历史报道的早发性和晚发性cblC病例以及先前未报道的病例，我们试图描述cblC个体眼部特征的流行病学、临床特征和发病机制。这些数据表明，黄斑病变和伴有视力异常的眼球震颤极为常见，影响大多数早发性cblC儿童，通常在学龄前；斜视和视神经萎缩也相对常见。黄斑疾病进展的时间可能与出生后黄斑发育的关键时期一致。黄斑病变和视网膜疾病可能是亚临床的，仅与视力缺陷程度部分相关，并且尽管对生化异常进行了积极治疗，视力恶化仍可能持续进展。在疾病的晚发性形式中，视力丧失和眼部并发症似乎很少见。最后，我们讨论了诊断和描述cblC个体眼部疾病的研究策略，探索了可能减轻眼部疾病进展和严重程度的治疗途径，并提出了一项临床监测指南，用于监测cblC儿童和成人眼部疾病的进展。
