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

作者信息

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

机构信息

Center for Metabolic Diseases, Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.

Tulane University Medical School, Hayward Genetics Center, New Orleans, LA, USA.

出版信息

J Inherit Metab Dis. 2016 Sep;39(5):713-723. doi: 10.1007/s10545-016-9945-x. Epub 2016 Jun 10.

DOI:10.1007/s10545-016-9945-x

PMID:27287710

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.

摘要