Mohammed AlOwain1,2, Ola Ali Khalifa3, Zahra Al Sahlawi4, Maged H Hussein5, Raashda A Sulaiman1,2, Moeen Al-Sayed1,2, Zuhair Rahbeeni1,2, Zuhair Al-Hassnan1,2, Hamad Al-Zaidan1,2, Hachemi Nezzar6,7, Iftetah Al Homoud8, Abdelmoneim Eldali9, Brian Altonen10, Bedour S Handoom11, Joyce N Mbekeani12,13. 1. Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre , Riyadh , Saudi Arabia. 2. College of Medicine, Alfaisal University , Riyadh , Saudi Arabia. 3. Genetics Unit, Pediatrics Department, Ain Shams University , Cairo , Egypt. 4. Department of Pediatrics and Metabolic/Genetic Diseases, Salmaniya Medical Complex , Manama , Kingdom of Bahrain. 5. Department of Medicine, King Faisal Specialist Hospital and Research Center , Riyadh , Saudi Arabia. 6. Image-Guided Clinical Neurosciences and Connectomics (IGCNC), Université d'Auvergne , Clermont-Ferrand , France. 7. Department of Ophthalmology, Dubai Hospital , Dubai , United Arab Emirates. 8. Department of Neurosciences, King Faisal Specialist Hospital and Research Centre , Riyadh , Saudi Arabia. 9. Department of Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Centre , Riyadh , Saudi Arabia. 10. Department of Biostatistics, Research Administration, Health & Hospitals Corporation , New York , NY , USA. 11. Department of Nutrition Services, King Faisal Specialist Hospital and Research Centre , Riyadh , Saudi Arabia. 12. Department of Surgery (Ophthalmology), Jacobi Medical Centre , Bronx , NY , USA. 13. Department of Ophthalmology & Visual Sciences, Albert Einstein College of Medicine , Bronx , NY , USA.
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.
Background: Classical MMA, caused by methylmalonyl-CoA mutasedeficiency, 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.