Abstract
Introduction
Alpha-1,3-glucosyltransferase congenital disorder of glycosylation (ALG6-CDG) is a congenital disorder of glycosylation. The original patients were described with hypotonia, developmental disability, epilepsy, and increased bleeding tendency.
Methods
Based on Euroglycan database registration, we approached referring clinicians and collected comprehensive data on 41 patients.
Results
We found hypotonia and developmental delay in all ALG6-CDG patients and epilepsy, ataxia, proximal muscle weakness, and, in the majority of cases, failure to thrive. Nine patients developed intractable seizures. Coagulation anomalies were present in <50 % of cases, without spontaneous bleedings. Facial dysmorphism was rare, but seven patients showed missing phalanges and brachydactyly. Cyclic behavioral change, with autistic features and depressive episodes, was one of the most significant complaints. Eleven children died before the age of 4 years due to protein losing enteropathy (PLE), sepsis, or seizures. The oldest patient was a 40 year-old Dutch woman. The most common pathogenic protein alterations were p.A333V and p.I299Del, without any clear genotype–phenotype correlation.
Discussion
ALG6-CDG has been now described in 89 patients, making it the second most common type of CDG. It has a recognizable phenotype and a primary neurologic presentation.
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Abbreviations
- ALG6:
-
Alpha-1,3-glucosyltransferase
- CDG:
-
Congenital disorder of glycosylation
- TIEF:
-
Transferrin isoelectric focusing
- PLE:
-
Protein-losing enteropathy
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Acknowledgments
The authors are thankful for the Euroglycanet and EURO-CDG networks
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All authors were compliant and followed the ethical guidelines, according to the requirements of JIMD
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Communicated by: Marc Patterson
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Supplementary Table 1
Mutations described in alpha-1,3-glucosyltransferase 6 (ALG6) according to the Exome Aggregation Consortium (ExAC) database. Missense, splice site, and frameshift mutations (178 in total) were ranked by allele frequency. (The 3 or 5′ untranslated region and intronic and silent variants were filtered out.) The three common variants in our patients are highlighted. They rank 9th, 22nd, and 107th for the c.257 + 5G > A, p.A333V, and p.I299Del respectively. (XLSX 40 kb)
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Morava, E., Tiemes, V., Thiel, C. et al. ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies. J Inherit Metab Dis 39, 713–723 (2016). https://doi.org/10.1007/s10545-016-9945-x
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DOI: https://doi.org/10.1007/s10545-016-9945-x