Ku Cristy A, Ng Jacqueline K, Karr Daniel J, Reznick Leah, Harding Cary O, Weleber Richard G, Pennesi Mark E
a Casey Eye Institute, Oregon Health & Science University , Portland , Oregon , USA.
b Molecular and Medical Genetics , Oregon Health & Science University , Portland , Oregon , USA.
Ophthalmic Genet. 2016 Dec;37(4):404-414. doi: 10.3109/13816810.2015.1121500. Epub 2016 Mar 15.
Cobalamin C disease (cblC), which leads to methylmalonic acidemia with homocystinuria, is the most common inherited disorder of vitamin B12 metabolism. Reported ocular findings associated with cblC have been maculopathy, pigmentary retinopathy, and optic nerve atrophy. Cobalamin A disease (cblA) which causes an isolated methylmalonic acidemia without homocystinuria is rarer than cblC. This is the first detailed report of the ocular findings associated with cblA. We also describe the spectrum of ocular findings in our cblC patients.
A case series describing the ophthalmologic clinical course of six patients with a diagnosis of cobalamin C type and one patient with cobalamin A type of methylmalonic acidemia. Patients were diagnosed through biochemical laboratory testing and genetic analysis was conducted on most patients. Longitudinal fundus findings, optical coherence tomography (OCT), autofluorescence, and electrophysiology were followed in the patients.
The cblA patient demonstrated a relatively mild ocular phenotype with late-onset and slowly progressing temporal disc pallor and peripapillary atrophy in the second decade of life. The patient maintained good visual acuity and central vision, without evidence of maculopathy. The six cblC patients demonstrated a range of ocular findings from unremarkable and mild phenotypes to significant retinopathy, including bull's eye maculopathy, severe maculopathy with punched out chorioretinal atrophy, peripheral bone spicules, and optic nerve atrophy.
The spectrum of ocular manifestations seen with inherited disorders of cobalamin metabolism is wide, ranging from mild optic nerve atrophy to severe macular or retinal degeneration. This heterogeneity may in part reflect the associated biochemical phenotype, such as that observed between our cblA and cblC patients. We also observed heterogeneity within the cblC type in agreement with previous reports.
钴胺素C病（cblC）可导致甲基丙二酸血症伴高胱氨酸尿症，是维生素B12代谢最常见的遗传性疾病。报道的与cblC相关的眼部表现有黄斑病变、色素性视网膜病变和视神经萎缩。钴胺素A病（cblA）导致孤立性甲基丙二酸血症而无高胱氨酸尿症，比cblC少见。这是关于与cblA相关的眼部表现的首份详细报告。我们还描述了我们的cblC患者的眼部表现谱。
本病例系列描述了6例诊断为钴胺素C型和1例钴胺素A型甲基丙二酸血症患者的眼科临床病程。患者通过生化实验室检测确诊，大多数患者进行了基因分析。对患者进行了纵向眼底检查、光学相干断层扫描（OCT）、自发荧光和电生理检查。
cblA患者表现出相对较轻的眼部表型，在生命的第二个十年出现迟发性且进展缓慢的颞侧视盘苍白和视盘周围萎缩。该患者视力和中心视力良好，无黄斑病变迹象。6例cblC患者表现出一系列眼部表现，从不明显和轻度表型到严重的视网膜病变，包括靶心黄斑病变、伴有凿孔状脉络膜视网膜萎缩的严重黄斑病变、周边骨针样改变和视神经萎缩。
钴胺素代谢遗传性疾病所见的眼部表现谱广泛，从轻度视神经萎缩到严重的黄斑或视网膜变性。这种异质性可能部分反映了相关的生化表型，如我们的cblA和cblC患者之间观察到的那样。我们还观察到cblC型内的异质性，与先前的报告一致。
