{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:26:19Z","timestamp":1792009579069,"version":"4.4.0"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,3,26]],"date-time":"2022-03-26T00:00:00Z","timestamp":1648252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a long chain fatty acid oxidation disorder, typically presenting with hypoketotic hypoglycaemia and liver dysfunction during fasting and intercurrent illness. Classical CPT1A deficiency is a rare disease, although a milder \u2018Arctic variant' (p.P479L) is common in the Inuit population. Since the introduction of expanded metabolic screening (EMS), the newborn screening programmes of Hawai'i and New Zealand (NZ) have detected a significant increase in the incidence of CPT1A deficiency. We report 22 individuals of Micronesian descent (12 in NZ and 10 in Hawai'i), homozygous for a <jats:italic>CPT1A<\/jats:italic> c.100T&gt;C (p.S34P) variant detected by EMS or ascertained following diagnosis of a family member. No individuals with the Micronesian variant presented clinically with metabolic decompensation prior to diagnosis or during follow\u2010up. Three asymptomatic homozygous adults were detected following the diagnosis of their children by EMS. CPT1A activity in cultured skin fibroblasts showed residual enzyme activity of 26% of normal controls. Secondly, we report three individuals from two unrelated Niuean families who presented clinically with symptoms of classic CPT1A deficiency, prior to the introduction of EMS. All were found to be homozygous for a <jats:italic>CPT1A<\/jats:italic> c.2122A&gt;C (p.S708R) variant. CPT1A activity in fibroblasts of all three individuals was severely reduced at 4% of normal controls. Migration pressure, in part due to climate change may lead to increased frequency of presentation of Pacific peoples to regional metabolic services around the world. Knowledge of genotype\u2013phenotype correlations in these populations will therefore inform counselling and treatment of those detected by newborn screening.<\/jats:p>","DOI":"10.1002\/jmd2.12271","type":"journal-article","created":{"date-parts":[[2022,3,26]],"date-time":"2022-03-26T08:38:00Z","timestamp":1648283880000},"page":"322-329","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genotype\u2013phenotype correlations in <scp>CPT1A<\/scp> deficiency detected by newborn screening in Pacific populations"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9368-9887","authenticated-orcid":false,"given":"Isaac","family":"Bernhardt","sequence":"first","affiliation":[{"name":"National Metabolic Service Auckland City Hospital and Starship Children's Hospital  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Glamuzina","sequence":"additional","affiliation":[{"name":"National Metabolic Service Auckland City Hospital and Starship Children's Hospital  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah K.","family":"Dowsett","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Hawai'i John A. Burns School of Medicine  Honolulu Hawai'i USA"},{"name":"Hawai'i Community Genetics  Honolulu Hawai'i USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne","family":"Webster","sequence":"additional","affiliation":[{"name":"Newborn Metabolic Screening Unit Auckland City Hospital  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlef","family":"Knoll","sequence":"additional","affiliation":[{"name":"Chemical Pathology (Section New Born Screening) Auckland City Hospital  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Human Genetics Society of Australasia  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Maeda","sequence":"additional","affiliation":[{"name":"Hawai'i Community Genetics  Honolulu Hawai'i USA"},{"name":"State of Hawai'i Department of Health Children with Special Health Needs Program  Honolulu Hawai'i USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Callum","family":"Wilson","sequence":"additional","affiliation":[{"name":"National Metabolic Service Auckland City Hospital and Starship Children's Hospital  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-018-9448-1"},{"key":"e_1_2_9_3_1","volume-title":"GeneReviews\u00ae","author":"Bennett MJ","year":"2005"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.12.018"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.197"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115090"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2011_94"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.06.017"},{"key":"e_1_2_9_9_1","unstructured":"Collaborative Laboratory Integrated Reports (CLIR). Website available online:https:\/\/clir.mayo.edu\/. Accessed September 132021."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.09.016"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2020.01.010"},{"key":"e_1_2_9_12_1","volume-title":"Infant Nutrition and Child Health on Tarawa, Kiribati: a Nutrition Anthropological Approach [Thesis (MA)]","author":"Christensen PM","year":"1995"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310130200"},{"key":"e_1_2_9_14_1","unstructured":"ClinVar. Website available online:https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/Accessed November 72021."},{"key":"e_1_2_9_15_1","first-page":"81","article-title":"Genomic medicine must reduce, not compound, health inequities: the case for hauora\u2010enhancing genomic resources for New Zealand","volume":"131","author":"Robertson SP","year":"2018","journal-title":"N Z Med J"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9106-6"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.4238\/vol9-3gmr834"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/app5.7"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12271","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmd2.12271","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12271","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T04:50:12Z","timestamp":1692679812000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.12271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,26]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1002\/jmd2.12271"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.12271","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"value":"2192-8312","type":"print"},{"value":"2192-8312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,26]]},"assertion":[{"value":"2021-09-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}