Gerth Christina, Morel Chantal F, Feigenbaum Annette, Levin Alex V
Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Canada.
J AAPOS. 2008 Dec;12(6):591-6. doi: 10.1016/j.jaapos.2008.06.008. Epub 2008 Oct 10.
To assess and compare longitudinal visual function and retinal morphology in patients with methylmalonic aciduria with homocystinuria, cobalamin C type (cblC), and identified mutations in the MMACHC gene.
Vision function, anterior segment, and fundi were evaluated in patients with homozygous or compound heterozygous MMACHC mutations. Best-corrected visual acuity, full-field electroretinogram (ERG), refractive error, and retinopathy were assessed and compared for different genotypes and ages at onset, defined as early (<1 year of age) or late (>5 years).
We identified 7 patients (homozygous mutation: 6 of 7; compound heterozygous mutations: 1 of 7) between the ages of 3 months and 20.6 years. Six patients were reexamined after 3.2 to 11.5 years (mean, 6.5) Ocular phenotype ranged from normal to severely compromised visual function. Visual acuity was reduced from 0.2 logMAR to counting fingers and from 0.0 to 0.3 logMAR in the early- (3 of 7) and in the late-onset group (4 of 7), respectively. No retinopathy was evident in the late-onset group. Only patients with the homozygous c.547_548 delGT mutations (n = 2) demonstrated advanced retinopathy associated with cone-rod or rod-cone dysfunction. Retinopathy occurred despite systemic treatment for cblC.
Ocular phenotype in patients with cblC is variable. Ocular involvement seems to be correlated with age at onset. Patients with early-onset cblC developed generally progressive retinal disease ranging from subtle retinal nerve fiber layer loss to advanced macular and optic atrophy with "bone spicule" pigmentation. Patients with late-onset disease showed no definite evidence of retinal degeneration.
评估并比较钴胺素C型甲基丙二酸尿症伴高胱氨酸尿症（cblC）患者以及已鉴定出MMACHC基因突变患者的纵向视觉功能和视网膜形态。
对纯合或复合杂合MMACHC基因突变患者的视觉功能、眼前节和眼底进行评估。对不同基因型和发病年龄（分为早发型（<1岁）或晚发型（>5岁））的最佳矫正视力、全视野视网膜电图（ERG）、屈光不正和视网膜病变进行评估和比较。
我们确定了7例年龄在3个月至20.6岁之间的患者（纯合突变：7例中的6例；复合杂合突变：7例中的1例）。6例患者在3.2至11.5年（平均6.5年）后接受了复查。眼部表型从正常到严重受损的视觉功能不等。早发型组（7例中的3例）和晚发型组（7例中的4例）的视力分别从0.2 logMAR降至数指，以及从0.0降至0.3 logMAR。晚发型组未发现视网膜病变。只有携带纯合c.547_548 delGT突变的患者（n = 2）表现出与锥杆或杆锥功能障碍相关的晚期视网膜病变。尽管对cblC进行了全身治疗，但仍发生了视网膜病变。
cblC患者的眼部表型是可变的。眼部受累似乎与发病年龄相关。早发型cblC患者通常会发展为进行性视网膜疾病，范围从轻微的视网膜神经纤维层缺失到晚期黄斑和视神经萎缩并伴有“骨针”状色素沉着。晚发型疾病患者未显示视网膜变性的确切证据。
