{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:24:44Z","timestamp":1788305084021,"version":"build-2803163510"},"reference-count":11,"publisher":"Wiley","issue":"S3","license":[{"start":{"date-parts":[[2010,5,20]],"date-time":"2010-05-20T00:00:00Z","timestamp":1274313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glycogen storage disease type III (GSD III) results from mutations of the <jats:italic>AGL<\/jats:italic> gene encoding the glycogen debrancher enzyme. The disease has clinical and biochemical heterogeneity reflecting the severity of the <jats:italic>AGL<\/jats:italic> mutations. We sought to characterise the molecular defects in our cohort of Irish patients with GSD III. Fifteen patients from eight unrelated Irish families were identified: six males and nine females. The age ranged from 2\u201339 years old, and all presented in the first 3 years of life. Four patients (of three families) had mild disease with hepatomegaly, mild hypoglycaemia and normal creatine kinase (CK) levels. Five families had more severe disease, with liver and skeletal muscle involvement and elevated CK. Eleven different mutations were identified amongst the eight families. Of the 11, six were novel: p.T512fs, p.S736fs, p.A1400fs, p.K1407fs, p.Y519X and p.D627Y. The family homozygous for p.A1400fs had the most severe phenotype (early\u2010onset hypoglycaemia, massive hepatomegaly, myopathy and hypertrophic cardiomyopathy before age 2 years), which was not halted by aggressive carbohydrate and protein supplementation. Conversely, the only missense mutation identified in the cohort, p.D627Y, was associated with a mild phenotype. The phenotypic diversity in our GSD III cohort is mirrored by the allelic heterogeneity. We describe two novel null mutations in exon 32 in two families with severe GSD III resistant to current treatment modalities. Knowledge of the specific mutations segregating in this cohort may allow for the development of new therapeutic interventions.<\/jats:p>","DOI":"10.1007\/s10545-010-9096-4","type":"journal-article","created":{"date-parts":[[2010,5,19]],"date-time":"2010-05-19T10:44:43Z","timestamp":1274265883000},"page":"215-218","source":"Crossref","is-referenced-by-count":17,"title":["Glycogen storage disease type III in the Irish population"],"prefix":"10.1002","volume":"33","author":[{"given":"Ellen","family":"Crushell","sequence":"first","affiliation":[{"name":"National Centre for Inherited Metabolic Disorders Children's University Hospital Temple St. Dublin 1 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen P.","family":"Treacy","sequence":"additional","affiliation":[{"name":"National Centre for Inherited Metabolic Disorders Children's University Hospital Temple St. Dublin 1 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Dawe","sequence":"additional","affiliation":[{"name":"Sheffield Molecular Genetics Service Sheffield Children's NHS Foundation Trust Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Durkie","sequence":"additional","affiliation":[{"name":"Sheffield Molecular Genetics Service Sheffield Children's NHS Foundation Trust Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Beauchamp","sequence":"additional","affiliation":[{"name":"Sheffield Molecular Genetics Service Sheffield Children's NHS Foundation Trust Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,5,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.06.007"},{"key":"e_1_2_6_3_1","first-page":"1521","volume-title":"The metabolic and molecular bases of inherited disease","author":"Chen YT","year":"2001"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-006-0045-x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1967.tb00133.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100380200000"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10347"},{"key":"e_1_2_6_8_1","article-title":"Neuromuscular forms of glycogenosis Type III: nine mutations in AGL","volume":"897","author":"Lucchiari S","year":"2006","journal-title":"Hum Mut; Mutation in brief"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050646"},{"issue":"1","key":"e_1_2_6_10_1","first-page":"165","article-title":"Molecular genetic diagnosis of glycogen storage disease (GSD) type III: experience from a large international cohort","volume":"31","author":"Santer R","year":"2008","journal-title":"J Inherit Metab Dis"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.1999.2953"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/1566524024605752"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-010-9096-4","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T06:22:17Z","timestamp":1694758937000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-010-9096-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5,20]]},"references-count":11,"journal-issue":{"issue":"S3","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["10.1007\/s10545-010-9096-4"],"URL":"https:\/\/doi.org\/10.1007\/s10545-010-9096-4","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,5,20]]}}}