TY - JOUR
T1 - ALG6-CDG
T2 - a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies
AU - Morava, Eva
AU - Tiemes, Vera
AU - Thiel, Christian
AU - Seta, Nathalie
AU - de Lonlay, Pascale
AU - de Klerk, Hans
AU - Mulder, Margot
AU - Rubio-Gozalbo, Estela
AU - Visser, Gepke
AU - van Hasselt, Peter
AU - Horovitz, Dafne D. G.
AU - Moura de Souza, Carolina Fischinger
AU - Schwartz, Ida V. D.
AU - Green, Andrew
AU - Al-Owain, Mohammed
AU - Uziel, Graciella
AU - Sigaudy, Sabine
AU - Chabrol, Brigitte
AU - Spronsen, van, Franc-Jan
AU - Steinert, Martin
AU - Komini, Eleni
AU - Wurm, Donald
AU - Bevot, Andrea
AU - Ayadi, Addelkarim
AU - Huijben, Karin
AU - Dercksen, Marli
AU - Witters, Peter
AU - Jaeken, Jaak
AU - Matthijs, Gert
AU - Lefeber, Dirk J.
AU - Wevers, Ron A.
PY - 2016/9
Y1 - 2016/9
N2 - 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.
AB - 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.
KW - CONGENITAL DISORDER
KW - GLYCOSYLATION
KW - GENE
KW - CDG
KW - MUTATION
U2 - 10.1007/s10545-016-9945-x
DO - 10.1007/s10545-016-9945-x
M3 - Article
SN - 0141-8955
VL - 39
SP - 713
EP - 723
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 5
ER -