Sudden death of a four-day-old newborn due to mitochondrial trifunctional protein/long-chain 3-hydroxyacyl-coa dehydrogenase deficiencies and a systematic literature review of early deaths of neonates with fatty acid oxidation disorders

Drole Torkar, Ana (author), Klinc, Ana (author), Ranković, Branislava (author), Debeljak, Maruša (author), Kovač, Jernej (author), Battelino, Tadej (author), Žerjav-Tanšek, Mojca (author), Grošelj, Urh (author)

Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies have been a part of the Slovenian newborn screening (NBS) program since 2018. We describe a case of early lethal presentation of MTPD/LCHADD in a term newborn. The girl was born after an uneventful pregnancy and delivery, and she was discharged home at the age of 3 days, appearing well. At the age of 4 days, she was found without signs of life. Resuscitation was not successful. The NBS test performed using tandem mass spectrometry (MS/MS) showed a positive screen for MTPD/LCHADD. Genetic analysis performed on a dried blood spot (DBS) sample identified two heterozygous variants in the HADHA gene: a nucleotide duplication introducing a premature termination codon (p.Arg205Ter) and a nucleotide substitution (p.Glu510Gln). Post-mortem studies showed massive macro-vesicular fat accumulation in the liver and, to a smaller extent, in the heart, consistent with MTPD/LCHADD. A neonatal acute cardiac presentation resulting in demise was suspected. We conducted a systematic literature review of early neonatal deaths within 14 days postpartum attributed to confirmed fatty acid oxidation disorders (FAODs), which are estimated to account for 5% of sudden infant deaths. We discuss the pitfalls of the NBS for MTPD/LCHADD.

• Language: English
• Keywords: MTP deficiency, MTPD, LCHAD deficiency, LCHADD, fatty acid oxidation disorder, FAOD, sudden infant death, newborn, newborn screening, NBS
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 15 str.
• Numbering: Vol. 11, Iss. 1, art. 9
• PID: 20.500.12556/RUL-176896
• UDC: 616-053.2
• ISSN on article: 2409-515X
• DOI: 10.3390/ijns11010009
• COBISS.SI-ID: 233271043
• Publication date in RUL: 15.12.2025

Record is a part of a journal

• Title: International journal of neonatal screening
• Shortened title: Int. j. neonatal screen.
• Publisher: MDPI AG
• ISSN: 2409-515X
• COBISS.SI-ID: 525322521

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: pomanjkanje MTP, MTPD, pomanjkanje LCHAD, LCHADD, motnja oksidacije maščobnih kislin, FAOD, nenadna smrt dojenčka, novorojenček, presejalni pregled novorojenčkov, NBS

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0343
• Name: Etiologija, zgodnje odkrivanje in zdravljenje bolezni pri otrocih in mladostnikih