[MIM 609 016]

Pathology of the ß-oxidation of long chain fatty acids. Autosomal recessive transmission. A specific mutation (G1528C) is very frequent (90 

% of the modified  alleles) in LCHAD deficiency patients. 

This enzyme is one of the components of the mitochondrial trifunctional protein and constitutes the first stage of the ß-oxidation of long chain fatty acids: in its absence, the fasting patient presents hypoglycemia without ketonemia and long-chain fatty acids accumulate in the tissue. In the absence of treatment or in case of important catabolism (fever, fasting, stress): hypotonia, liver dysfunction, cardiomyopathy.

Most patients secondarily develop a retinopathy and a peripheral neuropathy. Heterozygous mothers may develop a HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) in the third trimester of pregnancy when the fetus is affected. 

Treatment:  a low fat diet (long chain fatty acids must represent less than 10% of the daily caloric intake, 10 to 20 % being provided as medium-chain fatty acid ) and rich in carbohydrates. Dietary supplements of carnitine and of 3-hydroxybutyrate (synthetic ketone body used as substitute for the ketone bodies that cannot be synthetized in case of anomaly of the β-oxidation of the fatty acids). Avoid prolonged fasting.

Anesthetic implications: 

preoperative echocardiography; glucose infusion (5 or even 10 %, to avoid a lipolysis) at the beginning of the fasting period; usual dose of carnitine on the morning of the procedure; monitor blood glucose levels.

The use of propofol is controversial. Increased risk of "propofol infusion syndrome" (PRIS) ?

Use preferably a solution containing medium-chain fatty acids (the Diprivan© formulation  essentially contains long chain fatty acids) and avoid using it in continuous infusion as propofol inhibits complex II of the respiratory chain and intramitochondrial transport of long-chain fatty acids by carnitine. Avoid succinylcholine: risk of rhabdomyolysis. No risk of malignant hyperthermia. A continuous infusion of propofol in a solution containing long chain fatty acids has been used without problem for short-term sedation (40 minutes) in stable patients who were also receiving a glucose 10 % infusion. The estimated long-chain fatty acids intake in this case was approximately 10% of the daily dose allowed to the patient.

References : 

-         Steinman D, Knab J, Priebe H-J. 
Perioperative management of a child with long-chain 3 hydroxyacyl-CoA dehydrogenase deficiency (LCHAD).
Pediatr Anesth 2010; 20: 371-2.

-        Martin JM, Gilingham MB, Harding CO. 
Use of propofol for short duration procedures in children with long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TPF) deficiency. 
Molecular Genetics and Metabolism 2014; 112: 139-42.

Updated: April 2022