Retinal on-pathway deficit in congenital disorder of glycosylation due to phosphomannomutase deficiency.
OBJECTIVE
To describe novel electroretinographic (ERG) findings associated with congenital disorder of glycosylation due to phosphomannomutase deficiency (PMM2-CDG) (previously known as congenital disorder of glycosylation type 1a).


METHODS
Two male siblings with genetically confirmed PMM2-CDG underwent full-field ERG to a range of scotopic and photopic flash luminances that extended the International Society for Clinical Electrophysiology of Vision standard protocol and included scotopic 15-Hz flicker and photopic prolonged on-off stimulation.


RESULTS
Photopic prolonged ERGs were profoundly electronegative with absent b-waves but preserved oscillatory potentials. Prolonged off-responses and off-oscillatory potentials were preserved. Transient full-field photopic ERGs revealed a broad a-wave and narrow b-wave, and the photopic 30-Hz flicker ERG had a sawtooth waveform. The scotopic b-waves of both cases were attenuated to the fifth percentile, whereas scotopic a-wave amplitudes were at the 50th to 75th percentile, giving a reduced a:b ratio. The scotopic a-wave waveform was well defined to bright flash luminance. The number of scotopic oscillatory potentials was preserved, although amplitudes were smaller than average. Scotopic 15-Hz flicker ERGs were evident to a range of flash luminances and showed an expected phase cancellation between -1.5 and -1.0 log scotopic td (troland) • s, but phase increased only for the fast rod pathway.


CONCLUSIONS
We find, for the first time to our knowledge, an association of PMM2-CDG with a selective on-pathway dysfunction in the retina. This ERG phenotype localizes the site of retinal dysfunction to the on-bipolar synapse with photoreceptors. Modeling the unusual combination of ERG findings helps our understanding of the role of N -glycosylation at this synapse and provides a focus for future studies of potential intervention.
Clinical and Academic Department of Ophthalmology, Great Ormond Street Hospital for Children, London, England. dorothy.thompson@gosh.nhs.uk
Dorothy A
DA
Thompson
Ruth J
RJ
Lyons
Alki
A
Liasis
Isabelle
I
Russell-Eggitt
Herbert
H
Jägle
Stephanie
S
Grünewald
D000293:Adolescent; D055253:Color Vision / Q000502:physiology; D018981:Congenital Disorders of Glycosylation / Q000235:genetics / Q000503:physiopathology*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D006031:Glycosylation; D006801:Humans; D008297:Male; D055254:Night Vision / Q000502:physiology; D009991:Oscillometry; D017875:Phosphotransferases (Phosphomutases) / Q000378:metabolism / Q000172:deficiency; D010775:Photic Stimulation; D017354:Point Mutation; D012160:Retina / Q000201:enzymology / Q000503:physiopathology*; D012164:Retinal Diseases / Q000235:genetics / Q000503:physiopathology*; D035781:Siblings; D014792:Visual Acuity / Q000502:physiology
D017875:Phosphotransferases (Phosphomutases); C519582:phosphomannomutase 2, human