Molecular and clinical delineation of patients with fatty acid oxidation disorder: A single center’s experience

Purpose: Mitochondrial fatty acid oxidation disorders (FAODs) comprise a diverse group of genetic diseases involving the transportation or oxidation of fatty acids. We aimed to delineate the clinical and genetic basis, attempting to unravel the complexities of the phenotype-genotype correlation. Materials and Methods: We analyzed 26 patients who were diagnosed with FAODs. The clinical presentations, biochemical findings (including plasma acylcarnitines), and molecular analyses were examined retrospectively. Results: FAODs were identified in 26 patients during the study period, comprising very long chain acyl-CoA dehydrogenase(VLCAD) deficiency (3 patients), medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (4 patients), primary carnitine deficiency (2 patients), long chain hydroxyacyl-CoA dehydrogenase (LCHAD)/mitochondrial trifunctional protein (MTP) deficiencies(3 patients), and short chain acyl-CoA dehydrogenase (SCAD) deficiency (14 patients). VLCAD and LCHAD were diagnosed based on symptoms such as recurrent rhabdomyolysis and cardiomyopathy, while the others were diagnosed through newborn screening and familial tests. For SCAD deficiency, 35.7% of patients presented with symptoms, while 64.3% showed no symptoms. Germline mutations of the gene responsible for each FAOD were identified: VLCAD deficiency(6 alleles), LCHAD/MTP deficiency (6 alleles), MCAD deficiency (8 alleles), SCAD deficiency (28 alleles), and primary carnitine deficiency (4 alleles). In MCAD deficiency, 2 out of 8 mutations were novel: c.[843A>T] (p.Arg28Ser) and c.[1189T>A](p.Tyr397Asn). Additionally, SCAD deficiency presented five novel mutations: c.[1130C>T] (p.Pro377Leu), c.[277C>A](p.Leu93Ile), c.[682G>A] (p.Glu228Lys), c.[700C>T] (p.Arg234Trp), and c.[431C>T] (p.Thr144lle). Conclusion: Our study revealed a wide spectrum of the genetic landscape of patients with FAODs in Korea.