Optic neuropathy in classical methylmalonic acidemia

ABSTRACT

Background: Classical MMA, caused by methylmalonyl-CoA mutase deficiency, may result in late-onset dysfunction in several organ systems. To date, 10 cases of optic neuropathy have been reported. The prevalence of optic neuropathy in visually asymptomatic patients has not been determined. This study sought to identify overt and subclinical optic neuropathy in a cohort with classical MMA.

Methods and Materials: Neuroophthalmic examinations were performed on 21 patients identified with classical MMA, older than 10years. Diagnosis of optic neuropathy was determined by a combination of visual acuity, optic nerve appearance and electrodiagnostic tests. Tabulated data were analyzed for association of variables using SAS software. Significance was set at p < .05.

Results: Two-thirds were Saudi nationals and one third, Syrian. Age range was 11-29years. Eleven (52.4%) patients had optic neuropathy. Nine (81.8%) of these were bilateral, seven (57.9% to 63.6%) reported decreased vision and four (33.1% to 36.4%) were asymptomatic. Two patients had catastrophic vision loss, following acute metabolic crises. Sixteen patients had chronic renal impairment while three had renal hypertension. Seventeen patients had short stature and eight, chronic pancreatitis. Methylmalonic acid levels ranged from 82 to 3,324µmol/L (Normal<1µmol/L). There was a significant association between optic neuropathy and female gender (p = .011) and none with age, nationality, renal impairment, pancreatitis or specific genotype.

Conclusion: Optic neuropathy was a frequent finding in classical MMA. It was often bilateral and some cases were sub-clinical, lacking visual symptoms. These findings have important management implications. Full ophthalmic evaluations should be performed early and regularly in patients with MMA, even when patients are asymptomatic.

KEYWORDS:

• Methylmalonic acidemia
• metabolic disorder
• methylmalonyl-CoA
• metabolic acidosis
• vision loss
• optic neuropathy

Acknowledgments

We are very grateful to our patients and their families and for their participation in this study. We would like to thank Hasan M. Omairah AAS COT OCT-C CRA, Chief ophthalmic photographer and Maaly Abdel-Fattah MD, PhD, Assistant Consultant in the Department of Ophthalmology, King Faisal Specialist Hospital, Riyadh, Saudi Arabia and Timothy Truong, BA, MS IV at Albert Einstein College of Medicine, Bronx, NY, USA for provision of data and technical support. This research was conducted with intramural funds provided by King Faisal Specialist Hospital and Research Center. We would like to thank KFSH&RC/Research Advisory Committee for their support.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.