|
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
|