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

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

Author information

1
Center for Metabolic Diseases, Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium. eva.morava@uzleuven.be.
2
Tulane University Medical School, Hayward Genetics Center, New Orleans, LA, USA. eva.morava@uzleuven.be.
3
Department of Pediatrics, Radboud University Medical Center, Nijmegen, The Netherlands.
4
Translational Metabolic Laboratory, Department Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
5
Center for Child and Adolescent Medicine, Kinderheilkunde I, University of Heidelberg, Heidelberg, Germany.
6
Biochimie Métabolique Hôpital Bichat-Claude Bernard, Paris, France.
7
Reference Center of Metabolism, Necker-Enfants Malades Hospital, APHP, Imagine Institute, University Paris-Descartes, Paris, France.
8
Department of Pediatrics, Erasmus MC - University Medical Center Rotterdam, Emma Hospital, Rotterdam, The Netherlands.
9
Department of Pediatrics, Free University Amsterdam, Amsterdam, The Netherlands.
10
Department of Pediatrics and Laboratory Genetic Metabolic Diseases, University of Maastricht, Maastricht, The Netherlands.
11
Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
12
Medical Genetics Service, Porto Alegre, RS, Brazil.
13
National Centre for Medical Genetics, Dublin, Ireland.
14
Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
15
University of Milan, Institute of Neurology, Milan, Italy.
16
Département de Génétique Médicale, Hôpital Timone Enfant, Marseille, France.
17
Neuropediatrics Unit, Childrens Hospital CHU Timone, Marseille, France.
18
Division of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands.
19
Sozialpädiatrisches Zentrum, Neuropädiatrie, Klinik für Kinder- und Jugendmedizin, Dortmund, Germany.
20
Kinderklinik Villingen, Schwarzwald-Baar-Klinikum, Villingen, Germany.
21
Department of Pediatrics, Klinikum Saarbrücken, Saarbrücken, Germany.
22
Department of Pediatric Neurology and Developmental Medicine, Universal Children's Hospital Tübingen, Tübingen, Germany.
23
Centre for Human Metabolomics, North-West University, Potchefstroom, South Africa.
24
Center for Metabolic Diseases, Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
25
Laboratory for Molecular Diagnosis, Center for Human Genetics, University of Leuven, Leuven, Belgium.
26
Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands.
27
Translational Metabolic Laboratory, Department Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. ron.wevers@radboudumc.nl.

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.

PMID:
27287710
DOI:
10.1007/s10545-016-9945-x
[Indexed for MEDLINE]

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