Table 2.
FAOD manifestations, age of onset, and presentation/symptoms
| Manifestations | Contributing FAOD | Age of onset | Presentation/symptoms |
|---|---|---|---|
| Cardiac | • LC-FAOD [9] | • Neonatal or early childhood [11] | • Left ventricular wall hypertrophy may be observed initially and can progress to dilated cardiomyopathy with or without cardiac arrhythmia [40] |
| - VLCADD | • May present later in life after periods of crisis [9] | • Sometimes accompanied by pericardial effusion | |
| - CPT-IID | • Sudden death | ||
| - LCHADD | |||
| - TFPD | |||
| Hepatic | • MCADD [9] | • Neonatal or early childhood [41] | • Reye-like symptoms: |
| • LC-FAOD | • Typically within the first 2 years of life | • Hepatic encephalopathy and microvesicular steatosis of the liver and other tissues [12, 41] | |
| - CPT-IAD | • May present later in life after periods of crisis [12] | • Hypoketotic hypoglycemia | |
| - CPT-IID | • Hepatic dysfunction, characterized by jaundice, pale stools, enlarged liver, cholestasis (high bilirubin and c-GT, slight elevation of transaminases, normal platelet function), and axial hypotonia [23, 42] | ||
| - LCHADD | • Signs of adrenergic symptoms and/or impairment of the nervous system, including lethargy, seizures, apnea, or coma [11, 43, 44] | ||
| - CACTD | |||
| Muscular | • All FAOD [9] | • Early childhood [45] | • Myalgia (muscle pain) [15, 26] |
| • May present later in life provoked by endurance type activity, fasting, physiologic stress | • Hypotonia (muscle weakness) | ||
| • Exercise intolerance | |||
| • Myoglobinuria | |||
| • Different degrees of rhabdomyolysis (ranging from subclinical rise of creatine kinase through myoglobinuria to acute renal failure) | |||
| Neurologic | • LC-FAOD [46] | • Neuropathy presents subtly and is not usually detectable until later in life (teens into adulthood) as the disease progresses [23, 47, 48] | • Slow, progressive sensorimotor polyneuropathy, along with limb-girdle myopathy with recurrent episodes of myoglobinuria |
| - Generalized TFPD | • Neuropsychological manifestations are detectable earlier, as children miss key developmental milestones [49] | • Can present with autism spectrum disorders or intellectual disabilities [49, 50] | |
| - Isolated LCHADD | |||
| • All forms of FAOD have demonstrated links to intellectual disabilities | |||
| Retinopathy | • LC-FAOD [46] | • Retinopathy is not usually evident until later in life [51] | • Patients experience progressive, irreversible vision loss, including decreased color vision, low-light vision, and vision in the center of the field of view [48] |
| - Generalized TFPD | • Changes in the retina can be detected at around year 2 | ||
| - Isolated LCHADD | |||
| Other affected organ systems [52]: | • Lung: TFPD/CPT-IID | • Case reports have suggested respiratory distress in neonates | • Lung disease and respiratory distress have been reported anecdotally, and animal models with LC-FAOD have presented with altered breathing mechanics |
| • Kidney: VLCADD/CPT-IID | • Reports have shown the potential for chronic kidney disease throughout life | • Renal cysts and fibrosis, typically seen in chronic end-stage kidney disease, have been reported in some patients | |
| • Immune: VLCADD | • Laboratory studies have suggested a potential link between FAOD and immune response | • Murine studies have indicated that FAOD may cause chronic, low-grade inflammation or an exaggerated immune response to pathogens |
c-GT gamma-glutamyl transpeptidase, CACTD carnitine-acylcarnitine translocase deficiency, CPT-IAD/CPT-IID carnitine palmitoyltransferase I/II deficiency, FAOD fatty acid oxidation disorder, LC-FAOD long-chain fatty acid oxidation disorders, LCHADD long-chain L-3 hydroxyacyl-CoA dehydrogenase deficiency, MCADD medium-chain acyl-CoA dehydrogenase deficiency, TFPD tri-functional protein deficiency, VLCADD very-long-chain acyl-CoA dehydrogenase deficiency