IllnessFatty acid oxidation disorders, differential diagnosis

NGS +

[Sanger]

Fatty acid oxidation defects (FAODs) are inborn errors of metabolism due to disruption of either mitochondrial β-oxidation or fatty acid transport via the carnitine transport pathway. The symptomatology of a FAOD depends on the specific disorder, although common elements can be observed that ultimately require similar therapeutic strategies. Early signs of FAODs in the neonatal period with severe symptoms include cardiomyopathy, whereas in infancy and childhood liver dysfunction and hypoketotic hypoglycemia are common. Episodic rhabdomyolysis is often the initial presentation during or after adolescence; however, these symptoms can occur at any age in most FAODs. Therefore, the broad spectrum of clinical presentations of these conditions ranges from lethal neonatal cardiomyopathy in the first days of life to chronic skeletal myopathy or even potentially benign courses. Virtually all FAODs are exclusively inherited autosomal recessively. With the exception of sequence variants of unclear significance, the results of DNA studies are unequivocal. Accordingly, a negative molecular genetic result excludes the clinically defined diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1424/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331364/

• Alias: Fatty acid oxidation disorders
• Alias: Metabolic disease due to fatty acid oxidation disorder
• Allelic: Hyperinsulinemic hypoglycemia, familial, 4 (HADH)
• 3-hydroxyacyl-CoA dehydrogenase deficiency (HADH)
• ACAD9 deficiency (ACAD9)
• Acyl-CoA dehydrogenase, medium chain, deficiency of (ACADM)
• Acyl-CoA dehydrogenase, short-chain, deficiency of (ACADS)
• CPT II deficiency, infantile (CPT2)
• CPT deficiency, hepatic, type IA (CPT1A)
• Carnitine deficiency, systemic primary (SLC22A5)
• Carnitine palmitoyltransferase I [CPTI] deficiency (CPT1A)
• Carnitine-acylcarnitine translocase deficiency (SLC25A20)
• Fatty liver, acute, of pregnancy (HADHA)
• Glutaric acidemia IIA (ETFA)
• Glutaric acidemia IIB (ETFB)
• Glutaric acidemia IIC (ETFDH)
• HELLP syndrome, maternal, of pregnancy (HADHA)
• LCHAD deficiency (HADHA)
• Mitochondrial complex I deficiency due to ACAD9 deficiency (ACAD9)
• Mitochondrial trifunctional protein deficiency (HADHA)
• Trifunctional protein deficiency (HADHB)
• VLCAD deficiency (ACADVL)