Optic neuropathy in methylmalonic acidemia and propionic acidemia

Background Methylmalonic acidemia (MMA) and propionic acidemia (PA) are rare hereditary disorders of protein metabolism, manifesting early in life with ketoacidosis and encephalopathy and often resulting in chronic complications. Optic neuropathy (ON) has been increasingly recognised in both conditions, mostly through isolated case reports or small cases series. We here report the clinical features and visual outcomes of a case series of paediatric patients with a diagnosis of MMA or PA.
Methods Retrospective observational case series. A database of patients attending the Willink Biochemical Genetics unit in Manchester was interrogated. Fifty-three patients had a diagnosis of either isolated MMA or PA, of which 12 had been referred for ophthalmic review.
Results Seven patients had clinical findings compatible with ON. Visual outcomes in these patients were poor, with slow clinical progression or stability over time in five cases with follow-up. Presentation was acute in a context of metabolic crisis in two of the cases. Four patients with ON had electrodiagnostics showing absent pattern evoked potentials, with one showing a preserved flash response. All four showed marked attenuation of the dark-adapted electroretinogram with better preservation of the light-adapted response.
Conclusions Our study suggests that ON is under-reported in patients with MMA and PA. Clinical presentation can be acute or insidious, and episodes of acute metabolic decompensation appear to trigger visual loss. Photoreceptor involvement may coexist. Active clinical surveillance of affected patients is important as comorbidities and cognitive impairment may delay diagnosis.