A 12-year-old girl had poor vision in both eyes since childhood. Visual acuity was counting fingers with associated nystagmus. The electroretinogram was nonrecordable. Her medical history was notable for failure to thrive, methylmalonic aciduria, and homocystinuria. Genetic testing revealed mutations in the MMACHC gene.
These findings are consistent with cobalamin C deficiency–associated retinopathy (Figure).1,2 In this condition, the normal conversion of cobalamin (vitamin B12) to its coenzymatically active derivatives, deoxyadenosyl-cobalamin and methylcobalamin, does not occur. The lack of deoxyadenosyl-cobalamin results in a deficiency in the breakdown of odd chain fatty acids, manifesting as methylmalonic aciduria. A deficiency of methylcobalamin eliminates the production of methionine, resulting in homocystinuria.3 Although supplementation with cobalamin and methionine has been suggested, variable responses are seen, and the retinal degeneration typically progresses.2,4