{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T06:27:20Z","timestamp":1763447240426,"version":"3.45.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>\n                    Carnitine palmitoyltransferase II (CPT II) deficiency is a rare inherited disorder of mitochondrial oxidation of long-chain fatty acids (LCFA). Carnitine is the sole carrier of LCFA, which is transferred to the cellular mitochondria for\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -oxidation; CPT II plays a vital role in this process. Three phenotypic forms of CPT II deficiency exist: lethal neonatal (LNF), severe infantile hepato-cardio-muscular, and mild adult myopathic forms. The LNF is the most severe type of CPT II deficiency. Management should be guided by shared decision-making with parents, taking into account the severity of the disease, the goals of care, and the quality of life for both the patient and their family. We present a consanguineous couple with two siblings in consecutive pregnancies with LNF of CPT II deficiency who exhibited similar symptoms, both antenatally and postnatally. Antenatal assessments revealed cardiomegaly, ventriculomegaly, and polycystic kidneys. The first sibling received all supportive measures, including extracorporeal life support, but succumbed. Parents, counseled antenatally by the perinatal palliative care team, opted for comfort care for the second sibling, who passed away on day 3 of life. Cardiac, renal, and cerebral malformations were consistent in fetal and neonatal ultrasound scans of both siblings, who had biochemical and molecular diagnoses, confirming CPT II deficiency. The fetal imaging signs served as reliable indicators for early diagnosis, especially in the background of consanguinity. We present the cases of the siblings, including a literature review on fetal and neonatal characteristics, as well as the biochemical and molecular features of CPT II deficiency.\n                  <\/jats:p>","DOI":"10.3389\/fped.2025.1648282","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T06:23:06Z","timestamp":1763446986000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Lethal neonatal form of CPT II deficiency in consecutive pregnancies: fetal-neonatal characteristics, biochemical and molecular review"],"prefix":"10.3389","volume":"13","author":[{"given":"Y. Y.","family":"Tan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. G.","family":"Tewani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. J.","family":"Anand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. X.","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. S.","family":"Rajadurai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Chandran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2422","DOI":"10.1016\/j.bbamcr.2016.01.023","article-title":"Carnitine transport and fatty acid oxidation","volume":"1863","author":"Longo","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.3390\/molecules25081784","article-title":"Muscle carnitine palmitoyltransferase II (CPT II) deficiency: a conceptual approach","volume":"25","author":"Joshi","year":"2020","journal-title":"Molecules"},{"key":"B3","doi-asserted-by":"publisher","first-page":"SD01","DOI":"10.7860\/JCDR\/2015\/13600.6560","article-title":"Neonatal carnitine palmitoyltransferase II deficiency: a lethal entity","volume":"9","author":"Malik","year":"2015","journal-title":"J Clin Diagn Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e251321","DOI":"10.1136\/bcr-2022-251321","article-title":"Do renal and cardiac malformations in the fetus signal carnitine palmitoyltransferase II deficiency? A rare lethal fatty acid oxidation defect","volume":"19","author":"Tan","year":"2022","journal-title":"BMJ Case Rep"},{"key":"B5","doi-asserted-by":"publisher","first-page":"101170","DOI":"10.1016\/j.ymgmr.2024.101170","article-title":"A case study of lethal neonatal CPT II deficiency: novel insights from genetic analysis","volume":"41","author":"Tran","year":"2024","journal-title":"Mol Genet Metab Rep"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1212\/01.WNL.0000055901.58642.48","article-title":"Carnitine palmitoyltransferase II deficiency: molecular and biochemical analysis of 32 patients","volume":"60","author":"Wieser","year":"2003","journal-title":"Neurology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1126\/science.182.4115.929","article-title":"Muscle carnitine palmitoyltransferase deficiency and myoglobinuria","volume":"182","author":"DiMauro","year":"1973","journal-title":"Science"},{"key":"B8","article-title":"Carnitine palmitoyltransferase II Deficiency. [Updated 2019 Jan 3]","volume-title":"GeneReviews\u00ae [Internet]","author":"Wieser","year":"2004"},{"key":"B9","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1002\/ajmg.1457","article-title":"Antenatal presentation of carnitine palmitoyltransferase II deficiency","volume":"102","author":"Elpeleg","year":"2001","journal-title":"Am J Med Genet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1111\/cge.12593","article-title":"Diagnostic pitfall in antenatal manifestations of CPT II deficiency","volume":"89","author":"Boemer","year":"2016","journal-title":"Clin Genet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1042\/bj2690409","article-title":"Evidence that the sensitivity of carnitine palmitoyl transferase I to inhibition by malonyl-CoA is an important site of regulation of hepatic fatty acid oxidation in the fetal and newborn rabbit. Perinatal development and effects of pancreatic hormones in cultured rabbit hepatocytes","volume":"269","author":"Prip-Buus","year":"1990","journal-title":"Biochem J"},{"key":"B12","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1203\/01.PDR.0000161413.42874.74","article-title":"Long-chain fatty acid oxidation during early human development","volume":"57","author":"Oey","year":"2005","journal-title":"Pediatr Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1006\/mgme.1999.2938","article-title":"Carnitine palmitoyltransferase deficiencies","volume":"68","author":"Bonnefont","year":"1999","journal-title":"Mol Genet Metab"},{"key":"B14","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1002\/pd.713","article-title":"Prenatal diagnosis of carnitine palmitoyltransferase 2 deficiency in chorionic villi: a novel approach","volume":"23","author":"Vekemans","year":"2003","journal-title":"Prenat Diagn"},{"key":"B15","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/S0022-3476(95)70073-0","article-title":"Lethal neonatal deficiency of carnitine palmitoyltransferase II associated with dysgenesis of the brain and kidneys","volume":"127","author":"North","year":"1995","journal-title":"J Pediatr"},{"key":"B16","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1002\/mus.10217","article-title":"Phenotypic variability among first-degree relatives with carnitine palmitoyltransferase II deficiency","volume":"26","author":"Vladutiu","year":"2002","journal-title":"Muscle Nerve"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2248","DOI":"10.1161\/01.CIR.100.22.2248","article-title":"Arrhythmias and conduction defects as presenting symptoms of fatty acid oxidation disorders in children","volume":"100","author":"Bonnet","year":"1999","journal-title":"Circulation"},{"key":"B18","doi-asserted-by":"publisher","first-page":"3251","DOI":"10.3390\/molecules24183251","article-title":"Carnitine inborn errors of metabolism","volume":"24","author":"Almannai","year":"2019","journal-title":"Molecules"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.3389\/fgene.2019.01052","article-title":"Expanded newborn screening for inborn errors of metabolism by tandem mass spectrometry in Suzhou, China: disease spectrum, prevalence, genetic characteristics in a Chinese population","volume":"10","author":"Wang","year":"2019","journal-title":"Front Genet"},{"key":"B20","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1007\/s004310100802","article-title":"\u201cAdult\u201d form of muscular carnitine palmitoyltransferase II deficiency: manifestation in a 2-year-old child","volume":"160","author":"Gempel","year":"2001","journal-title":"Eur J Pediatr"},{"key":"B21","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1002\/humu.10201","article-title":"Correlation between genotype, metabolic data, and clinical presentation in carnitine palmitoyltransferase 2 (CPT2) deficiency","volume":"21","author":"Thuillier","year":"2003","journal-title":"Hum Mutat"},{"key":"B22","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/s100380300001","article-title":"A novel splice site mutation in neonatal carnitine palmitoyl transferase II deficiency","volume":"48","author":"Smeets","year":"2003","journal-title":"J Hum Genet"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1097\/01.LAB.0000098428.51765.83","article-title":"Carnitine palmitoyltransferase II deficiency: a clinical, biochemical, and molecular review","volume":"83","author":"Sigauke","year":"2003","journal-title":"Lab Invest"},{"key":"B24","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1172\/JCI115090","article-title":"Infantile form of carnitine palmitoyltransferase II deficiency with hepatomuscular symptoms and sudden death. Physiopathological approach to carnitine palmitoyltransferase II deficiencies","volume":"87","author":"Demaugre","year":"1991","journal-title":"J Clin Invest"},{"key":"B25","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.jns.2013.12.026","article-title":"Carnitine palmitoyltransferase II (CPT II) deficiency: genotype-phenotype analysis of 50 patients","volume":"338","author":"Joshi","year":"2014","journal-title":"J Neurol Sci"},{"key":"B26","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.mam.2004.06.004","article-title":"Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects","volume":"25","author":"Bonnefont","year":"2004","journal-title":"Mol Aspects Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1002\/jimd.12199","article-title":"Therapeutic potential of triheptanoin in metabolic and neurogenerative disease","volume":"43","author":"Wehbe","year":"2020","journal-title":"J Inheri Metab Dis"},{"key":"B28","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.ymgme.2015.10.005","article-title":"Anaplerotic treatment of long-chain fat oxidation disorders with triheptanoin: review of 15 years experience","volume":"116","author":"Roe","year":"2015","journal-title":"Mol Genet Metab"},{"key":"B29","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/S1570-0232(03)00310-6","article-title":"Effect of supplementation of L-carnitine at a small dose on acylcarnitine profiles in serum and urine and the renal handling of acylcarnitines in a patient with multiple acyl-coenzyme A dehydrogenation defect","volume":"792","author":"Yoshino","year":"2003","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e41686","DOI":"10.1371\/journal.pone.0041686","article-title":"Long-chain acylcarnitines regulate the HERG channel","volume":"7","author":"Ferro","year":"2012","journal-title":"PLoS One"},{"key":"B31","doi-asserted-by":"publisher","first-page":"CD006659","DOI":"10.1002\/14651858.CD006659.pub3","article-title":"Carnitine supplementation for inborn errors of metabolism","volume":"2012","author":"Nasser","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"B32","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1007\/s10545-009-1126-8","article-title":"Treatment recommendations in long-chain fatty acid oxidation defects: consensus from a workshop","volume":"32","author":"Spiekerkoetter","year":"2009","journal-title":"J Inherit Metab Dis"},{"key":"B33","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1001\/archneur.62.1.37","article-title":"Muscle carnitine palmitoyltransferase II deficiency: clinical and molecular genetic features and diagnostic aspects","volume":"62","author":"Deschauer","year":"2005","journal-title":"Arch Neurol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"17","DOI":"10.2147\/RRN.S55353","article-title":"Current perspectives on neonatal hypoglycemia, its management, and cerebral injury risk","volume":"5","author":"Chandran","year":"2015","journal-title":"Res Rep Neonatol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1177\/08258597211046735","article-title":"Perinatal palliative care service: developing a comprehensive care package for vulnerable babies with life limiting fetal conditions","volume":"37","author":"Tewani","year":"2022","journal-title":"J Palliat Care"},{"key":"B36","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1056\/NEJMc0806334","article-title":"Bezafibrate for an inborn mitochondrial beta-oxidation defect","volume":"360","author":"Bonnefont","year":"2009","journal-title":"N Engl J Med"},{"key":"B37","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/GIM.0b013e3181c5e6f7","article-title":"Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects","volume":"12","author":"El-Hattab","year":"2010","journal-title":"Genet Med"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1648282\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T06:23:10Z","timestamp":1763446990000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1648282\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,18]]},"references-count":37,"alternative-id":["10.3389\/fped.2025.1648282"],"URL":"https:\/\/doi.org\/10.3389\/fped.2025.1648282","relation":{},"ISSN":["2296-2360"],"issn-type":[{"type":"electronic","value":"2296-2360"}],"subject":[],"published":{"date-parts":[[2025,11,18]]},"article-number":"1648282"}}