{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:40:11Z","timestamp":1787586011474,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T00:00:00Z","timestamp":1623628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pyruvate kinase deficiency (PKD) is a rare, autosomal recessive red blood cell enzyme disorder, which leads to lifelong hemolytic anemia and associated complications from the disease and its management.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An international, multicenter registry enrolled 124 individuals younger than 18\u00a0years old with molecularly confirmed PKD from 29 centers. Retrospective and prospective clinical data were collected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was a wide range in the age at diagnosis from 0 to 16\u00a0years. Presentation in the newborn period ranged from asymptomatic to neonatal jaundice to fulminant presentations of fetal distress, myocardial depression, and\/or liver failure. Children &lt;5\u00a0years old were significantly more likely to be transfused than children &gt;12 to &lt;18\u00a0years (53% vs. 14%, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.0006), which correlated with the timing of splenectomy. Regular transfusions were most common in children with two severe <jats:italic>PKLR<\/jats:italic> variants. In regularly transfused children, the nadir hemoglobin goal varied considerably. Impact on quality of life was a common reason for treatment with regular blood transfusions and splenectomy. Splenectomy increased the hemoglobin and decreased transfusion burden in most children but was associated with infection or sepsis (12%) and thrombosis (1.3%) even during childhood. Complication rates were high, including iron overload (48%), perinatal complications (31%), and gallstones (20%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>There is a high burden of disease in children with PKD, with wide practice variation in monitoring and treatment. Clinicians must recognize the spectrum of the manifestations of PKD for early diagnostic testing, close monitoring, and management to avoid serious complications in childhood.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.29148","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T13:20:56Z","timestamp":1623676856000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Pyruvate kinase deficiency in children"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5909-0800","authenticated-orcid":false,"given":"Satheesh","family":"Chonat","sequence":"first","affiliation":[{"name":"Department of Pediatrics Emory University School of Medicine, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan W.","family":"Eber","sequence":"additional","affiliation":[{"name":"Schwerpunktpraxis f\u00fcr P\u00e4diatrische H\u00e4matologie\u2010Onkologie  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Holzhauer","sequence":"additional","affiliation":[{"name":"Charit\u00e9 University Medicine, Pediatric Hematology and Oncology  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Kollmar","sequence":"additional","affiliation":[{"name":"Klinikum Kassel GmbH  Kassel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Holmes","family":"Morton","sequence":"additional","affiliation":[{"name":"Central Pennsylvania Clinic for Special Children &amp; Adults  Belleville Pennsylvania USA"},{"name":"Lancaster General Hospital  Lancaster Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertil","family":"Glader","sequence":"additional","affiliation":[{"name":"Lucile Packard Children's Hospital Stanford University  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellis J.","family":"Neufeld","sequence":"additional","affiliation":[{"name":"St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan M.","family":"Yaish","sequence":"additional","affiliation":[{"name":"Primary Children's Hospital University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1582-2886","authenticated-orcid":false,"given":"Jennifer A.","family":"Rothman","sequence":"additional","affiliation":[{"name":"Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukta","family":"Sharma","sequence":"additional","affiliation":[{"name":"Children's Mercy School of Medicine University of Missouri  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaddanapudi","family":"Ravindranath","sequence":"additional","affiliation":[{"name":"Children's Hospital of Michigan Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Wang","sequence":"additional","affiliation":[{"name":"DDC Clinic for Special Needs Children  Middlefield Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicky R.","family":"Breakey","sequence":"additional","affiliation":[{"name":"McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujit","family":"Sheth","sequence":"additional","affiliation":[{"name":"Weill Cornell Medical College New York Presbyterian Hospital  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A.","family":"Bradeen","sequence":"additional","affiliation":[{"name":"The University of Vermont Children's Hospital  Burlington Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"Al\u2010Sayegh","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber\/Boston Children's Cancer and Blood Disorder Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3571-6538","authenticated-orcid":false,"given":"Wendy B.","family":"London","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber\/Boston Children's Cancer and Blood Disorder Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael F.","family":"Grace","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber\/Boston Children's Cancer and Blood Disorder Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V19.3.267.267"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI106539"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196801112780203"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI106324"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.165.3893.601"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.11.3585"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.22118"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24088"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25325"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-10-810796"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.161166"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15758"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.214692"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16724"},{"issue":"1","key":"e_1_2_10_16_1","first-page":"75","article-title":"Hydrops fetalis associated with red cell pyruvate kinase deficiency","volume":"1","author":"Hennekam RC","year":"1990","journal-title":"Genet Couns"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-0834"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13128"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.092460"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH15-05-0381"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.1107"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.196295"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1902678"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.11.4323.bloodjournal86114323"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.177857"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2016.87"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.200"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.10945"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.29148","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pbc.29148","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.29148","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T06:21:32Z","timestamp":1692685292000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.29148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,14]]},"references-count":27,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1002\/pbc.29148"],"URL":"https:\/\/doi.org\/10.1002\/pbc.29148","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,14]]},"assertion":[{"value":"2021-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e29148"}}