• Fatty acid oxidation comes to the fore in long-term hunger and in situations where energy needs such as febrile illness.
• In addition, fatty acid is the main fuel of heart muscle and exercising muscle tissue. Ketones, which are the end products of fatty acid oxidation in the liver, cannot be used in the liver, they are transported out of the liver for use by the brain.
• For long chain acyl CoA to enter the outer membrane of the mitochondria from the cytosol, it must be esterified with the enzyme carnitine palmitoyl transferase-I (CPT-I) (not necessary for short and medium chain fatty acids).
• Acyl carnitine, which enters the inner membrane of mitochondria with carnitine/acyl carnitine translocase, is deesterified by CPT-2 and the resulting acyl CoA enters the beta-oxidation chain.
• The beta oxidation process is related to the length of the fatty acid chain and is initiated by dehydrogenases (LCAD; Long chain Acyl CoA Dehydrogenase, MCAD; Medium chain Acyl CoA Dehydrogenase, SCAD; Case chain Acyl CoA Dehydrogenase).
• After acyl CoA shortens well, it turns into acetyl CoA and enters the Krebs cycle to provide energy.
FATTY ACID OXIDATION DEFECTS
Clinical findings
- The most common clinical finding is fatal hypoglycemic hypoketotic coma (especially in cases of prolonged fasting, infection, stress)
- Chronic cardiomyopathy, muscle weakness and skeletal muscle myopathy
- Rhabdomyolysis
- SIDS
- Liver failure
- Reye's syndrome-like findings
Laboratory Findings
ketones low
Ammonia high
No significant metabolic acidosis
Glucose: Low
Transaminase: High
PT time: Long
Total carnitine: Low
dicarboxylic excretion in urine
differential diagnosis
Demonstration of enzyme deficiency in fibroblasts and leukocytes (definitive diagnosis)
Reye's syndrome
Treatment
acute treatment
- Glucose Infusion
- No lipids
- Carnitine
chronic treatment
- Avoiding prolonged starvation
- Frequent feeding
• The most common fatty acid oxidation defect is MCAD (medium chain acyl CoA dehydrogenase) deficiency.
• Acute fatty liver or HELLP syndrome with preeclampsia (hemolysis, elevated hepatic enlargement, thrombocytopenia) may be seen during pregnancy due to the toxic effect of fatty acids in mothers of infants with LCHAD (long chain hydroxy acyl CoAdehydrogenase) and CPT-1 deficiency.
• Since hyperinsulinism due to increased glutamate dehydrogenase activity is observed in cases with SCHAD (short chain hydroxy acyl CoA dehydrogenase) deficiency, diazoxide is also used in the treatment of hypoglycemia.
• Primary carnitine deficiency progresses with progressive cardiomyopathy and carnitine replacement is used in its treatment. However, in CPT-I deficiency, muscle involvement is not observed, and carnitine replacement is not required since it is the only fatty acid oxidation defect that does not show secondary carnitine deficiency.
• While renal cystic dysplasia, facial anomalies and cerebral anomalies are seen in the lethal neonatal form of CPT-2 deficiency, the adult form progresses with episodic rhabdomyolysis that starts after adolescence. CPT-2 deficiency is the most common cause of hereditary myoglobinurias.
• ETF or ETF dehydrogenase deficiency with electron transfer chain disorder is called glutaric acidemia type II. ETF and ETF dehydrogenase transport electrons from some dehydrogenation steps to the mitochondrial electron transfer chain. These reactions are 4 enzymes including VLCAD, MCAD, SCAD, glutaryl CoA dehydrogenase and isovaleryl CoA dehydrogenase in branched chain amino acid metabolism.
• Glutaric acidemia type 2 therefore presents as a combination of both fatty acid oxidation and amino acid metabolism defect. As with fatty acid oxidation defects, hypoketotic hypoglycemia, cardiomyopathy, and dicarboxylic aciduria are present. But unlike isovaleric acidemia, acidosis is severe and there is the smell of sweaty feet in the urine, as in isovaleric acidemia. Another important feature is facial dysmorphism and polycystic kidney, just like neonatal CPT-II deficiencies. High-dose riboflavin is used to treat mild forms.
