Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy with Severe Ganglion Cell Loss

Abstract

Purpose: To describe the retinal structure and function of a group of patients with cobalamin C (cbl C) disease.

Methods: Patients with cbl C disease underwent complete ophthalmic examinations, color and near-infrared retinal imaging as well as spectral domain optical coherence tomography (SD-OCT). Longitudinal data was available in most patients.

Results: Results: Patients (n=11, age 6 months to 15 years) carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. With the exception of one patient who had a normal retinal exam, all patients showed a maculopathy. Measurable visual acuities ranged from 20/200 to 20/400. Nystagmus was present in 8/11 patients. In general, retinal changes were first observed before one year of age and progressed within months to a well-established maculopathy. Wide-spread retinal degeneration was noted in older patients (n=4; >7 years of age). SD-OCT showed macular thinning, predominantly of the ganglion cell layer (GCL), accompanied by outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central retinal disease. Large well-demarcated areas of foveal chrorioretinal atrophy with the appearance of pseudo-colobomas were documented in three patients.

Conclusions: This subset of patients with cbl C and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy. There was some indication that the severe GCL loss exceeded that expected for a primary photoreceptor disorder, pointing to the GCL as the primary site of disease. An abnormally thickened inner retina supports a remodeling response to degeneration and/or interference with normal development in this condition.