Fatty Acid Oxidation Disorders Detected by Newborn Screening: Clinical, Biochemical and Genetic Spectrum in a Single‐Center Cohort
Abstract
ABSTRACT Newborn screening (NBS) has significantly improved early detection and survival in fatty acid oxidation disorders (FAODs). However, the expanding phenotypic spectrum challenges prognostic stratification, and long‐term morbidity remains incompletely characterized. We conducted an observational, retrospective, single‐center study of patients with FAODs identified through NBS and followed between 2011 and 2024. Clinical, biochemical, genetic, and nutritional data were extracted from medical records. Correlations between biochemical markers, enzymatic activity, and clinical outcomes were analyzed. The study was approved by the Research Committee of the Instituto de Investigación, Hospital 12 de Octubre (Madrid). Sixty‐five patients were included: 42 MCADD, 11 VLCADD, 5 LCHADD, 2 CPT1D, 3 CPT2D, 1 CACTD, and 1 MADD. Median age at last follow‐up was 7.2 years (range 0.4–13.6). Two patients died during follow‐up (overall mortality 3.1%). In MCADD, confirmatory C8 concentrations correlated with residual enzyme activity and metabolic decompensations. In VLCADD, NBS and confirmatory C14:1 levels correlated with enzyme activity but not with clinical severity. VLCADD showed marked clinical heterogeneity, whereas LCHADD patients had the highest disease burden and required the most intensive nutritional management. Overall, 40% of patients experienced at least one metabolic decompensation, occurring significantly more frequently in LC‐FAOD than in MCADD. Neuropsychological manifestations were observed in 16.9% of patients. In summary, NBS markedly improves survival in FAODs, but morbidity remains substantial, particularly in LC‐FAOD. Current biochemical markers are useful for early risk stratification but remain insufficient to predict long‐term clinical severity. These findings support individualized multidisciplinary follow‐up, including specialized nutritional care and systematic neuropsychological assessment.