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Table 2 FAOD manifestations, age of onset, and presentation/symptoms

From: Clinical manifestations and management of fatty acid oxidation disorders

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
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]
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
  1. 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