Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss.

Cobalamin C (cblC) disease is the most common inborn error of vitamin B12 metabolism with an estimated incidence of ∼1:100,000 live births. Patients with this autosomal recessive disorder show homocysteinemia, homocystinuria, and methylmalonic aciduria and acidemia.1–3 The disease is associated with neurologic, hematologic, ophthalmologic, cardiovascular, dermatologic, respiratory, and facial abnormalities and is subclassified as early onset, when presentation occurs before a year of age, and late onset, for patients presenting later in life.1,4–9 Mutations in the MMACHC (methylmalonic aciduria cblC type, with homocystinuria) gene, which encodes a protein involved in cobalamin cofactor synthesis, have been associated with cblC.4,9–11 The ocular phenotype has been described through case reports, a handful of case series, and a single histopathologic report.8,12–23 Ocular changes range from limited maculopathies to a progressive retina-wide degeneration and severe central vision loss. The exact mechanisms leading to the neurologic and/or ocular manifestations are currently unknown. We recently reported the detailed spectral-domain (SD) optical coherence tomography (OCT) structural phenotype of a young patient with cblC. Retinal structure was characterized by photoreceptor and ganglion cell loss, the presence of a thickened surface layer, and a remodeled inner retina in regions of severe degeneration.8 The maculopathy had developed from an initially normal retina into a well-stablished lesion within the first year of life, suggestive of interference with foveal development.8 To increase understanding of the visual dysfunction and retinal structural abnormalities resulting from cblC disease, we studied a group of patients with cblC disease and MMACHC mutations using measures of central vision, electrophysiology, and retinal structure. The results were compared to hereditary retinal degenerations with predominant macular involvement.