Glycogen storage disease type III: diagnosis, genotype, management, clinical course and outcome.
Glycogen storage disease type III (GSDIII) is a rare disorder of glycogenolysis due to AGL gene mutations, causing glycogen debranching enzyme deficiency and storage of limited dextrin. Patients with GSDIIIa show involvement of liver and cardiac/skeletal muscle, whereas GSDIIIb patients display only liver symptoms and signs. The International Study on Glycogen Storage Disease (ISGSDIII) is a descriptive retrospective, international, multi-centre cohort study of diagnosis, genotype, management, clinical course and outcome of 175 patients from 147 families (86 % GSDIIIa; 14 % GSDIIIb), with follow-up into adulthood in 91 patients. In total 58 AGL mutations (non-missense mutations were overrepresented and 21 novel mutations were observed) were identified in 76 families. GSDIII patients first presented before the age of 1.5 years, hepatomegaly was the most common presenting clinical sign. Dietary management was very diverse and included frequent meals, uncooked cornstarch and continuous gastric drip feeding. Chronic complications involved the liver (hepatic cirrhosis, adenoma(s), and/or hepatocellular carcinoma in 11 %), heart (cardiac involvement and cardiomyopathy, in 58 % and 15 %, respectively, generally presenting in early childhood), and muscle (pain in 34 %). Type 2 diabetes mellitus was diagnosed in eight out of 91 adult patients (9 %). In adult patients no significant correlation was detected between (non-) missense AGL genotypes and hepatic, cardiac or muscular complications. This study demonstrates heterogeneity in a large cohort of ageing GSDIII patients. An international GSD patient registry is warranted to prospectively define the clinical course, heterogeneity and the effect of different dietary interventions in patients with GSDIII.
Section of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, PO Box 30 001, 9700 RB, Groningen, The Netherlands.
Christiaan P
CP
Sentner
Section of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, PO Box 30 001, 9700 RB, Groningen, The Netherlands.
Irene J
IJ
Hoogeveen
Glycogen Storage Disease Program, University of Florida, Gainesville, FL, USA.
David A
DA
Weinstein
Department of Paediatrics, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
René
R
Santer
Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK.
Elaine
E
Murphy
Birmingham Children's Hospital, Birmingham, UK.
Patrick J
PJ
McKiernan
Department of Occupational and Public Health (DFAA), Tórshavn, Faroe Islands.
Ulrike
U
Steuerwald
Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
Nicholas J
NJ
Beauchamp
Department of Metabolic Diseases, Children's Memorial Health Institute, Warsaw, Poland.
Joanna
J
Taybert
Centre de Référence de Pathologie, Neuromusculaire Paris-Est, Institut de Myologie, GH Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
Pascal
P
Laforêt
Department of Genetics and Cytogenetics, AP-HP, Antoine Béclère University Hospital, University Paris Sud, Paris, France.
François M
FM
Petit
APHP, Hôpitaux Universitaires Paris Sud, hôpital Antoine Béclère, Centre de Référence des Maladies héréditaires du Métabolisme Hépatique, and Paris Sud University, Clamart, France.
Aurélie
A
Hubert
APHP, Hôpitaux Universitaires Paris Sud, hôpital Antoine Béclère, Centre de Référence des Maladies héréditaires du Métabolisme Hépatique, and Paris Sud University, Clamart, France.
Philippe
P
Labrune
Section of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, PO Box 30 001, 9700 RB, Groningen, The Netherlands.
G Peter A
GPA
Smit
Section of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, PO Box 30 001, 9700 RB, Groningen, The Netherlands. t.g.j.derks@umcg.nl.
Terry G J
TGJ
Derks
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006004:Glycogen Debranching Enzyme System / Q000235:genetics; D006010:Glycogen Storage Disease Type III / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D012189:Retrospective Studies; D055815:Young Adult
D006004:Glycogen Debranching Enzyme System; C030563:amylo-1,6-glucosidase