title: Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss.
abstract: OBJECTIVE
  To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease.
  
  
  METHODS
  Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients.
  
  
  RESULTS
  Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease.
  
  
  CONCLUSIONS
  Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC.
authors.affiliation: Scheie Eye Institute and the Perelman Center for Advanced Medicine, Department of Ophthamology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Lucas
authors.initials: L
authors.lastname: Bonafede
authors.affiliation: Department of Pediatrics, Section of Biochemical Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Can H
authors.initials: CH
authors.lastname: Ficicioglu
authors.affiliation: Scheie Eye Institute and the Perelman Center for Advanced Medicine, Department of Ophthamology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Leona
authors.initials: L
authors.lastname: Serrano
authors.affiliation: Scheie Eye Institute and the Perelman Center for Advanced Medicine, Department of Ophthamology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Grace
authors.initials: G
authors.lastname: Han
authors.affiliation: Scheie Eye Institute and the Perelman Center for Advanced Medicine, Department of Ophthamology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Jessica I W
authors.initials: JI
authors.lastname: Morgan
authors.affiliation: Division of Ophthalmology, The Children's Hospital of Philadelphia, Department of Ophthalmology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Monte D
authors.initials: MD
authors.lastname: Mills
authors.affiliation: Division of Ophthalmology, The Children's Hospital of Philadelphia, Department of Ophthalmology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Forbes
authors.affiliation: Division of Ophthalmology, The Children's Hospital of Philadelphia, Department of Ophthalmology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Stefanie L
authors.initials: SL
authors.lastname: Davidson
authors.affiliation: Division of Ophthalmology, The Children's Hospital of Philadelphia, Department of Ophthalmology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Gil
authors.initials: G
authors.lastname: Binenbaum
authors.affiliation: Department of Pediatrics, Section of Biochemical Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Paige B
authors.initials: PB
authors.lastname: Kaplan
authors.affiliation: Scheie Eye Institute and the Perelman Center for Advanced Medicine, Department of Ophthamology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Nichols
authors.affiliation: Department of Pediatrics, Ghent University and Ghent University Hospital, Ghent, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Verloo
authors.affiliation: Division of Ophthalmology, The Children's Hospital of Philadelphia, Department of Ophthalmology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States 5Department of Ophthalmology, Ghent University and Gh.
authors.forename: Bart P
authors.initials: BP
authors.lastname: Leroy
authors.affiliation: Scheie Eye Institute and the Perelman Center for Advanced Medicine, Department of Ophthamology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States 3Division of Ophthalmology, The Children's Hospital of.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Maguire
authors.affiliation: Scheie Eye Institute and the Perelman Center for Advanced Medicine, Department of Ophthamology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States 3Division of Ophthalmology, The Children's Hospital of.
authors.forename: Tomas S
authors.initials: TS
authors.lastname: Aleman
mesh_terms: D000293:Adolescent; D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications* / Q000175:diagnosis; D002648:Child; D002675:Child, Preschool; D004596:Electroretinography; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D012162:Retinal Degeneration / Q000175:diagnosis / Q000209:etiology*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D012720:Severity of Illness Index; D041623:Tomography, Optical Coherence / Q000379:methods; D014792:Visual Acuity