Retinal on-pathway deficit in congenital disorder of glycosylation due to phosphomannomutase deficiency.

Abstract

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.

• Authors: Dorothy A Thompson, Ruth J Lyons, Alki Liasis, Isabelle Russell-Eggitt, Herbert Jägle, Stephanie Grünewald
• Journal: Archives of ophthalmology (Chicago, Ill. : 1960) (Arch Ophthalmol) Vol. 130 Issue 6 Pg. 712-9 (Jun 2012) ISSN: 1538-3601 [Electronic] United States
• PMID: 22801829 (Publication Type: Case Reports, Journal Article)

Chemical References

• Phosphotransferases (Phosphomutases)
• phosphomannomutase 2, human

Topics

• Adolescent
• Color Vision (physiology)
• Congenital Disorders of Glycosylation (genetics, physiopathology)
• DNA Mutational Analysis
• Electroretinography
• Glycosylation
• Humans
• Male
• Night Vision (physiology)
• Oscillometry
• Phosphotransferases (Phosphomutases) (metabolism)
• Photic Stimulation
• Point Mutation
• Retina (enzymology, physiopathology)
• Retinal Diseases (genetics, physiopathology)
• Siblings
• Visual Acuity (physiology)