ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies

Eva Morava-Kozicz, Vera Tiemes, Christian Thiel, Nathalie Seta, Pascale de Lonlay, Hans de Klerk, Margot Mulder, Estela Rubio-Gozalbo, Gepke Visser, Peter van Hasselt, Dafne D.G. Horovitz, Carolina Fischinger Moura de Souza, Ida V.D. Schwartz, Andrew Green, Mohammed Al-Owain, Graciella Uziel, Sabine Sigaudy, Brigitte Chabrol, Franc Jan van Spronsen, Martin SteinertEleni Komini, Donald Wurm, Andrea Bevot, Addelkarim Ayadi, Karin Huijben, Marli Dercksen, Peter Witters, Jaak Jaeken, Gert Matthijs, Dirk J. Lefeber, Ron A. Wevers

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)713-723
Number of pages11
JournalJournal of Inherited Metabolic Disease
Volume39
Issue number5
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Morava-Kozicz, E., Tiemes, V., Thiel, C., Seta, N., de Lonlay, P., de Klerk, H., Mulder, M., Rubio-Gozalbo, E., Visser, G., van Hasselt, P., Horovitz, D. D. G., de Souza, C. F. M., Schwartz, I. V. D., Green, A., Al-Owain, M., Uziel, G., Sigaudy, S., Chabrol, B., van Spronsen, F. J., ... Wevers, R. A. (2016). ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies. Journal of Inherited Metabolic Disease, 39(5), 713-723. https://doi.org/10.1007/s10545-016-9945-x