Ocular manifestations of early-onset combined methylmalonic acidemia and mutations in MMCHC gene

Abstract Purpose: Combined MMA is related with retinopathy and optic neuropathy. We aimed to find the relationship of genotypes, the levels of metabolites and ocular damages in combined MMA.Methods: We retrospectively analyzed the ocular manifestations, gene tests and levels of organic acid metabolism in seven patients with early-onset combined MMA. Results: Seven patients aged 2 to 7 years old, revealed different gene mutations. Two patients with remarkable retinal degenerations had mutations in MMCHC gene, which were one heterozygous for c.567dupT p.Ile190Tyrfs*13, c.658_660del p.Lys220del, the other one with c.482G>A, p. R161Q, c.567dupT, p. I190Yfs*13 genotypes. Four patients present normal fundus, in whom one was homozygous for c.609G>A, p. W203X, the second one was heterozygous for c.609G>A, p. W203X, c.626dupT p.Thr210Aspfs*35, the third one with c.567dup, p.I190Yfs*13, c.606-641delins CTT, p.W203-R214delinsF, the last one with c.609G>A, p. Trp203*, c.615C>A, p. Tyr205*genotypes. There was one patient who was heterozygous for c.609G>A, p. Trp203*, c.615C>A, p. Tyr205* revealed light color of optic nerve but normal VEP. Elevated level of plasma homocysteine and normal levels of MMA concentrations and its metabolites revealed in two patients with remarkable retinal degenerations, whereas the levels of plasma homocysteine, MMA and its metabolites were normal in five patients without retinal disease.Conclusions: The mutations detected may be related to retinopathy and optic neuropathy in children with combined MMA. Metabolite levels may also affect the clinical manifestations.