Abstract
Fatty acid oxidation disorders (FAODs) are a group of rare diseases caused by deficiencies in the function of enzymes or proteins involved in the mitochondrial oxidation of fatty acids. This study aimed to analyze the incidence, disease spectrum, gene profile, and clinical phenotypes of FAODs in the southeastern coastal region of China. Between January 2016 and June 2024, acylcarnitine, genetic mutation, and clinical manifestation data were collected from patients diagnosed with FAOD through newborn screening. A total of 210,913 newborns were screened, identifying 36 cases of FAODs, with an overall incidence of 1 in 5,859. Primary carnitine deficiency (PCD) was the most prevalent FAOD, with an incidence of 1 in 9,587, followed by multiple acyl-CoA dehydrogenase deficiency (MADD). Moreover, we identified 32 mutations, including 5 novel variants. Patients with PCD who carried homozygous variants (R254*) of the SLC22A5 gene demonstrated significantly lower average free acylcarnitine levels than those with compound heterozygous variants (2.45 ± 1.27 µmol/L versus 4.42 ± 1.13 µmol/L, p < 0.05). In patients with MADD, rescreening revealed lower levels of characteristic acylcarnitines (C6, C8, C10, C12, and C14) compared with initial screening values, with 42.3% returning to normal levels. During long-term follow-up (approximately 6 years), all patients remained under clinical surveillance initiated based on their NBS diagnosis. One patient with PCD developed severe retinal detachment at age 5. Three patients with long-chain FAOD (two VLCADD, one CPT-IID) died following infections that triggered metabolic crises (ages 5 and 8 months, respectively). These fatal outcomes occurred despite early diagnosis and initiation of standard management protocols prompted by the NBS results. No other severe complications were observed in the surviving cohort. Our findings highlight the importance of developing screening protocols and clinical management strategies to improve outcomes for affected newborns.
Keywords:
Fatty acid oxidation disorders; Genetic variation; Multiple acyl-CoA dehydrogenase deficiency; Newborn screening; Primary carnitine deficiency; Tandem mass spectrometry.