title: Long-term visual outcome of methylmalonic aciduria and homocystinuria, cobalamin C type.
abstract: OBJECTIVE
  To describe the long-term ophthalmologic outcomes of patients with methylmalonic aciduria and homocystinuria, cobalamin C type (cblC).
  
  
  METHODS
  Retrospective case series.
  
  
  METHODS
  All patients with cblC referred to the Department of Ophthalmology of the Centre Hospitalier Universitaire Sainte-Justine from 1984 through 2012 were studied. Twelve such patients were identified.
  
  
  METHODS
  Clinical ophthalmic examinations, neuroimaging, electroretinography, and the results of MMACHC mutation analysis were reviewed retrospectively.
  
  
  METHODS
  We examined visual acuity, ocular alignment, presence of maculopathy and peripheral retinopathy, optic atrophy, and nystagmus. Photopic and scotopic electroretinograms were reviewed. We examined and compared mutations in the MMACHC gene. Neuroimaging abnormalities were compiled when available.
  
  
  RESULTS
  Twelve cblC patients were followed up from 2 to 23 years (average, 10 years). Eleven of 12 patients were diagnosed before the age of 1 year (range, birth-2 years). An initial ophthalmic examination was performed within the first year of age in 9 of 12 patients. Visual acuity at the time of presentation was variable, ranging from light perception to 20/20. Visual acuity was worse than 20/100 in 75% (9/12) of patients at last follow-up. Eight patients (67%) had obvious maculopathy on fundus examination. Other findings included peripheral retinopathy (8/12 [67%]), nystagmus (8/12 [67%]), strabismus (5/12 [42%]), and optic atrophy (6/12 [50%]). Funduscopic deterioration was documented in 1 patient, whereas electrophysiologic changes occurred in 4 patients. Neuroimaging results were available in 7 of the patients, revealing corpus callosum atrophy (7/7 [100%]) and periventricular white matter loss (6/7 [85%]).
  
  
  CONCLUSIONS
  Most children in our series had early-onset disease with neurologic manifestations and abnormal ophthalmologic examination results. Despite early treatment, many early-onset cblC patients have poor visual function.
authors.affiliation: Department of Ophthalmology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Gizicki
authors.affiliation: Department of Ophthalmology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Robert
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Canada.
authors.forename: Lilianne
authors.initials: L
authors.lastname: Gómez-López
authors.affiliation: Department of Ophthalmology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Canada.
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Orquin
authors.affiliation: Department of Medical Imaging, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Decarie
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Canada; Research Center, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Canada.
authors.forename: Grant A
authors.initials: GA
authors.lastname: Mitchell
authors.affiliation: Department of Ophthalmology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Canada.
authors.forename: Marie-Sylvie
authors.initials: MS
authors.lastname: Roy
authors.affiliation: Department of Ophthalmology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, Canada. Electronic address: lhospina@gmail.com.
authors.forename: Luis H
authors.initials: LH
authors.lastname: Ospina
mesh_terms: D000293:Adolescent; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D055253:Color Vision / Q000502:physiology; D004252:DNA Mutational Analysis; D003952:Diagnostic Imaging; D004596:Electroretinography; D005260:Female; D005500:Follow-Up Studies; D006712:Homocystinuria / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D055254:Night Vision / Q000502:physiology; D009759:Nystagmus, Pathologic / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D009896:Optic Atrophy / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D010088:Oxidoreductases; D012164:Retinal Diseases / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D012189:Retrospective Studies; D013285:Strabismus / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D014786:Vision Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D014792:Visual Acuity / Q000502:physiology*; D014806:Vitamin B 12 Deficiency / Q000151:congenital; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; C508359:MMACHC protein, human; D010088:Oxidoreductases