Ocular phenotype in patients with methylmalonic aciduria and homocystinuria, cobalamin C type.

PURPOSE: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.