We suggest testing for ALG1 mutations in unsolved CDG patients with a type 1 transferrin isoelectric focusing pattern, especially with epilepsy, severe visual loss and hemorrhagic/thrombotic events.
It has also been reported in some patients with ALG1-CDG, ALG3-CDG, ALG9-CDG, ALG6-CDG, ALG8-CDG, PIGA-CDG, DPM1-CDG, DPM2-CDG, B4GALT1-CDG, SLC35A2-CDG, COG1-CDG, COG5-CDG, COG7-CDG, and COG8-CDG.
The genes reported for CDG with NIHF for 15 distinct families include: PMM2 in 47% (7/15), ALG9 in 20% (3/15), ALG8 in 13% (2/15), ALG1 in 7% (1/15), MGAT2 in 7% (1/15), and COG6 7% (1/15).
Recently, we identified the first patient with a defect in the cytosolic-orientated GDP-mannose:Man(3-4) GlcNAc(2)-PP-dolichol alpha-1,2-mannosyltransferase (ALG11), who presented an accumulation of shortened dolichol-linked oligosaccharides leading to CDG-Ip (ALG11-CDG).
Arrest of fetal brain development, with image findings consistent with fetal brain disruption sequence, is a previously unreported phenotype of congenital microcephaly in ALG11-congenital disorder of glycosylation.
Ocular abnormalities are common in CDG, but there is no report of detailed ophthalmologic evaluation in patients with CDG type Ig in the literature.<b>Materials and Methods</b>: Retrospective chart review of a case of CDG type Ig with novel variant in the associated gene: ALG12.<b>Results</b>: In addition to typical systemic findings of CDG, our case was found to have exotropia, bilateralcataracts, and retinitis pigmentosa with extinguished electroretinography in photopic and scotopic conditions.<b>Conclusions</b>: We hope to extend the understanding of ALG12-related CDG type Ig with these ophthalmologic observations.
The skeletal features overlap with that previously reported for ALG3- and ALG12-CDG, suggesting that this subset of glycosylation disorders constitutes a new diagnostic group of skeletal dysplasias.