Long-chain fatty acid oxidation disorders: A review of newborn screening around the globe for LC-FAOD
Ethical Legal Social Issues (ELSI) Public Health and Policy
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Primary Categories:
- Public Health Genetics
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Secondary Categories:
- Public Health Genetics
Introduction:
Long-chain fatty acid oxidation disorders (LC-FAOD) are rare inborn errors of metabolism leading to serious consequences due to inability to utilize fat as a source of energy. Early detection by newborn screening (NBS) significantly decreases morbidity and mortality. An overview of NBS for LC-FAOD subtypes CACT, CPT I, CPT II, LCHAD, TFP (also known as MTP) and VLCAD by screening programs around the globe is presented.
Methods:
A review of LC-FAOD NBS programs was compiled in March 2024 from online resources and published literature and updated in August 2024 with information from a newly published systematic-review on the status of newborn bloodspot screening worldwide (Therrell et al 2024. PMID: 38920845). Findings were supplemented with expert author opinion on regional status of NBS for LC-FAOD. Current NBS methodology cannot differentiate among some LC-FAOD subtypes (CACT/CPT II, TFP/LCHAD), so additional subtypes may be detected which are not reported as part of NBS.
Results:
Conclusion:
NBS for LC-FAOD enables early diagnosis and treatment and significantly improves clinical outcomes in affected patients. Few countries universally screen for all 6 LC-FAOD disorders and discrepancies exist in NBS panels for LC-FAOD worldwide. It remains possible to miss LC-FAOD even with NBS, and access to confirmatory molecular testing is not uniform. Uncertain molecular findings from NBS could be aided by use of a new locus specific database for LC-FAOD gene variants (https://RareDiseaseGenes.com). Given incomplete availability of NBS, clinical signs and symptoms later in life warrant suspicion for LC-FAOD.
Long-chain fatty acid oxidation disorders (LC-FAOD) are rare inborn errors of metabolism leading to serious consequences due to inability to utilize fat as a source of energy. Early detection by newborn screening (NBS) significantly decreases morbidity and mortality. An overview of NBS for LC-FAOD subtypes CACT, CPT I, CPT II, LCHAD, TFP (also known as MTP) and VLCAD by screening programs around the globe is presented.
Methods:
A review of LC-FAOD NBS programs was compiled in March 2024 from online resources and published literature and updated in August 2024 with information from a newly published systematic-review on the status of newborn bloodspot screening worldwide (Therrell et al 2024. PMID: 38920845). Findings were supplemented with expert author opinion on regional status of NBS for LC-FAOD. Current NBS methodology cannot differentiate among some LC-FAOD subtypes (CACT/CPT II, TFP/LCHAD), so additional subtypes may be detected which are not reported as part of NBS.
Results:
Asia/Oceana: Australia, Japan, New Zealand and Taiwan screen for all 6 LC-FAOD, Philippines, Singapore, Thailand and Vietnam screen for 5, and South Korea screens for LCHAD. Pilot NBS programs in China (n≥ 7) include LC-FAOD.
Europe: Ten countries screen for all 6 LC-FAOD and >10 countries screen for ≥1 LC-FAOD. Eleven countries do not support LC-FAOD NBS.
Latin America: No country performs universal screening for all LC-FAOD. In 2 Brazilian states, NBS includes LC-FAOD. Costa Rica screens for VLCAD, LCHAD & CPT II. Uruguay pilots CPT I, VLCAD and LCHAD. Colombia and Mexico have limited pilots.
Middle East, Africa: Saudi Arabia screens for VLCAD; Kuwait for VLCAD, LCHAD and TFP; Qatar and Israel screen for all except CACT. UAE screens all 6 LC-FAOD. Lebanon NBS includes VLCAD, LCHAD and a third LC-FAOD.
US & Canada: All US states, DC, and 1 territory screen for VLCAD, LCHAD and TFP; 81% NBS for (universal or likely detected) CPT I, 92% for CPT II & CACT. All Canadian provinces and territories screen for VLCAD, LCHAD and TFP; CPT I CPT II, and CACT are included in NBS programs in 70% of provinces and 20% of territories.
Conclusion:
NBS for LC-FAOD enables early diagnosis and treatment and significantly improves clinical outcomes in affected patients. Few countries universally screen for all 6 LC-FAOD disorders and discrepancies exist in NBS panels for LC-FAOD worldwide. It remains possible to miss LC-FAOD even with NBS, and access to confirmatory molecular testing is not uniform. Uncertain molecular findings from NBS could be aided by use of a new locus specific database for LC-FAOD gene variants (https://RareDiseaseGenes.com). Given incomplete availability of NBS, clinical signs and symptoms later in life warrant suspicion for LC-FAOD.