{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:46:01Z","timestamp":1792032361747,"version":"4.4.0"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T00:00:00Z","timestamp":1623456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T00:00:00Z","timestamp":1623456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Idiopathic ketotic hypoglycemia (IKH) is a diagnosis of exclusion with glycogen storage diseases (GSDs) as a differential diagnosis. GSD IXa presents with ketotic hypoglycemia (KH), hepatomegaly, and growth retardation due to\n                    <jats:italic>PHKA2<\/jats:italic>\n                    variants. In our multicenter study, 12 children from eight families were diagnosed or suspected of IKH. Whole\u2010exome sequencing or targeted next\u2010generation sequencing panels were performed. We identified two known and three novel (likely) pathogenic\n                    <jats:italic>PHKA2<\/jats:italic>\n                    variants, such as p.(Pro869Arg), p.(Pro498Leu), p.(Arg2Gly), p.(Arg860Trp), and p.(Val135Leu), respectively. Erythrocyte phosphorylase kinase activity in three patients with the novel variants p.(Arg2Gly) and p.(Arg860Trp) were 15%\u201320% of mean normal. One patient had short stature and intermittent mildly elevated aspartate aminotransferase, but no hepatomegaly. Family testing identified two asymptomatic children and 18 adult family members with one of the\n                    <jats:italic>PHKA2<\/jats:italic>\n                    variants, of which 10 had KH symptoms in childhood and 8 had mild symptoms in adulthood. Our study expands the classical GSD IXa phenotype of\n                    <jats:italic>PHKA2<\/jats:italic>\n                    missense variants to a continuum from seemingly asymptomatic carriers, over KH\u2010only with phosphorylase B kinase deficiency, to more or less complete classical GSD IXa. In contrast to typical IKH, which is confined to young children, KH may persist into adulthood in the KH\u2010only phenotype of\n                    <jats:italic>PHKA2<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62383","type":"journal-article","created":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T04:04:00Z","timestamp":1623470640000},"page":"2959-2975","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>\n                      <i>PHKA2<\/i>\n                    <\/scp>\n                    variants expand the phenotype of phosphorylase B kinase deficiency to include patients with ketotic hypoglycemia only"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4694-5539","authenticated-orcid":false,"given":"Anne","family":"Benner","sequence":"first","affiliation":[{"name":"Hans Christian Andersen Children's Hospital, Odense University Hospital  Odense Denmark"},{"name":"Department of Clinical Research, Faculty of Health Sciences University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0569-2988","authenticated-orcid":false,"given":"Yazeid","family":"Alhaidan","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Faculty of Health Sciences University of Southern Denmark  Odense Denmark"},{"name":"Department of Clinical Genetics, Odense University Hospital  Odense Denmark"},{"name":"Department of Medical Genomics Research King Abdullah international medical research center, NGHA  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1278-2743","authenticated-orcid":false,"given":"Matthew A.","family":"Lines","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Alberta Children's Hospital University of Calgary  Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2096-4988","authenticated-orcid":false,"given":"Klaus","family":"Brusgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Faculty of Health Sciences University of Southern Denmark  Odense Denmark"},{"name":"Department of Clinical Genetics, Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1225-8087","authenticated-orcid":false,"given":"Diva D.","family":"De Leon","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes The Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Sparkes","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Alberta Children's Hospital University of Calgary  Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7944-8910","authenticated-orcid":false,"given":"Anja L.","family":"Frederiksen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of Clinical Medicine Aalborg University Hospital  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5330-6853","authenticated-orcid":false,"given":"Henrik T.","family":"Christesen","sequence":"additional","affiliation":[{"name":"Hans Christian Andersen Children's Hospital, Odense University Hospital  Odense Denmark"},{"name":"Department of Clinical Research, Faculty of Health Sciences University of Southern Denmark  Odense Denmark"},{"name":"OPAC, Odense Pancreas Center Odense University Hospital  Odense 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