title: Disturbed visual system function in methionine synthase deficiency.
abstract: BACKGROUND
  Isolated functional methionine synthase deficiency occurs in the cblE and cblG defects of methylcobalamin metabolism and is one of a number of causes of severely elevated plasma homocysteine. Clinical features are predominantly of a neurological nature but also include functional restriction of the visual system manifesting as loss of visual acuity and nystagmus. As yet, the origin and pathogenesis of impaired vision have not been explained.
  
  
  METHODS
  We investigated a patient who was proven by complementation analysis in cultured fibroblasts to belong to the cblG complementation group. Ganzfeld electroretinograms (ERG) and flash visual evoked potentials (VEP) were recorded over a period of 4 years.
  
  
  RESULTS
  Amplitudes of all International Society for Clinical Electrophysiology of Vision (ISCEV) standard responses were below normal. The greatest reductions were of rod response to 24 microV, of standard combined response (SC) b-wave to 120 microV, of oscillatory potentials (OP) to 5 microV, of cone response b-wave to 35 microV, and of 30 Hz flicker response to 8 microV. Except for SC and cone a-waves at age 2.5 and 3.5 years, as well as cone b-wave at 3.5 years, amplitudes remained at a subnormal level at follow-up examinations. Implicit times were slightly prolonged (SC b-wave 6 ms, OPs 2 ms, cone b-wave 2 ms, 30 Hz flicker 4 ms) or fell within the normal range. Responses of the flash VEP were severely deformed but reproducible.
  
  
  CONCLUSIONS
  This is the first report of detailed investigations of the visual system in a patient with isolated methionine synthase deficiency. Reduced oscillatory potentials suggest microvascular damage to the retina through homocysteine. Decreased photoreceptor function as well as ganglion cell loss as indicated by pathological flash VEPs may reflect a cytotoxic impact of homocysteine on neurons of the visual pathway.
authors.affiliation: Department of Paediatric Ophthalmology and Ophthalmogenetics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. charlotte.poloschek@klinik.uni-regensburg.de
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Poloschek
authors.forename: Brian
authors.initials: B
authors.lastname: Fowler
authors.forename: Renate
authors.initials: R
authors.lastname: Unsold
authors.forename: Birgit
authors.initials: B
authors.lastname: Lorenz
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000172:deficiency* / Q000235:genetics; D004596:Electroretinography; D005074:Evoked Potentials, Visual; D005816:Genetic Complementation Test; D006801:Humans; D007223:Infant; D008297:Male; D017949:Retinal Cone Photoreceptor Cells / Q000503:physiopathology*; D012164:Retinal Diseases / Q000201:enzymology* / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000503:physiopathology*; D014786:Vision Disorders / Q000503:physiopathology*; D014805:Vitamin B 12 / Q000031:analogs & derivatives
chemical_list: C019476:mecobalamin; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D014805:Vitamin B 12