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Jacqueline Ng, Daniel Karr, Leah Reznick, Mark Pennesi; Presentation and Progression of the Ocular Manifestations of Methylmalonic Acidemia in Children. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1332.
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© ARVO (1962-2015); The Authors (2016-present)
To describe the spectrum of ocular findings of methylmalonic acidemia (MMA) in children.
A review of patients was performed for a diagnosis of cobalamin-A (cba1) and cobalamin-C (cbc1) type disease. We identified seven cases of MMA (1 case of cba1 and 6 cases of cbc1 disease) and compiled clinical course, spectral-domain optical coherence tomography (SD-OCT), and electroretinogram (ERG) findings.
Three patients with confirmed MMACHC gene mutations had initial normal fundus exams. One case with heterozygous c.271dupA and novel invariant splicing donor site mutation presented at 8 months and developed optic atrophy and Bull’s eye maculopathy consistent with SD-OCT by 4 years old. ERG showed mildly decreased rod and cone amplitudes. One case with homozygous 615C>G (p.Y205X) mutation presented at 3 months and progressed to severe macular atrophy at 1 year confirmed on SD-OCT. The third patient with homozygous c.271dupA mutation remained stable. Two additional patients were siblings homozygous for MMACHC gene c.271_272dupA mutation. The older one presented at 3 years with optic atrophy, attenuated vessels, peripheral pigment dusting that progressed to bony spicules, and prominent Bull’s eye maculopathy that progressed to macular atrophy. ERG showed severely subnormal rod and cone responses. The younger one was diagnosed and started on treatment prenatally but presented at 7 months with a mild Bull’s eye maculopathy. The final patient presented with Bull’s eye maculopathy at 6 months that progressed to macular atrophy with peripheral pigment changes by 2 years. Initial ERG showed prolongation of the cone-rod implicit times but normal amplitudes that was stable at 2 years. The cba1 case showed initial mild peripapillary pigment epithelial mottling that progressed over 21 years to mild optic atrophy in both eyes with associated mild decreased ERG responses but intact vision.
This series suggests a natural history of initial normal fundus exams progressing to early optic atrophy, Bull’s eye maculopathy, and late findings of peripheral pigmentary changes in MMA. SD-OCT and ERG may be useful before onset of clinical findings. Systemic treatment did not halt progression, but early prenatal treatment may limit the severity of disease.
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