[MIM 201 450]

Acronym for Medium Chain Acyl-coenzymeA dehydrogenase Deficiency)

Most common mitochondrial disease of the metabolism of fatty acids. Autosomal recessive transmission (1/10,000 births, in the Caucasian populations) of the 1p31 ACADM\R gene mutations. Deficiency in the enzyme that initiates the medium chain ß-oxidation of fatty acids (C6-12). This failure  of using fatty acids causes hypoglycemia with hypocetosis when gluconeogenesis is insufficient to ensure the energic needs (fasting, infection). This also leads to the lack of production of ketone bodies (alternative energy substrate for the brain, myocardium, liver and muscles) and an accumulation of medium-chain acyl-CoA derivatives (cardiac toxicity).

Some countries have already organised systematic neonatal screening on DJ3. HELPP syndrome cases have been reported in mothers carrying fetuses with MCAD deficiency.

The clinical presentation depends on the residual capacity of the enzyme to metabolize the medium-chain fatty acids: this activity depends on the type of mutation.

• neonatal period: after 12 - 24 hours of life: lethargy, convulsions, encephalopathy or coma; hypoglycemia with hypocetosis, metabolic acidosis, hyperammonemia, cardiac arrhythmia
• childhood: between 3 and 24 months when night feeding is interrupted ,hypocetotic hypoglycemia  with hyperammonemia during prolonged fasting or in case of infection; sudden infant death
• later: digestive (vomiting) or neurological (drowsiness, encephalopathy) signs in the course of a banal infection, sometimes stress-induced rhabdomyolysis
• at any age: during catabolic stress (viral infection, fasting, alcohol intake for example) major hepatocellular failure with hepatic coma: pseudo Reye syndrome which can result in death (cerebral edema) or neurological sequelae. Liver biopsy: acute fatty liver. One can also find lipid deposits in the heart and kidneys. Sometimes, hyperuricemia, CPK level > 1000

Treatment :

- in case of acute crisis: symptomatic treatment, intake of glucose 10% (10 mg/kg/min) and L-carnitine (100 mg/kg/day)

- chronic treatment

1)         avoid triglyceride-rich milk and coconut

2) intake of L-carnitine: 20-50 mg/kg/day in 2 doses to avoid a secondary deficiency in carnitine

3) avoid prolonged fasting. For a child in good health do not exceed 3 to 4 h up to 1 month; 4 to 6 hours up to 4 months; 6 to 8 hours up to 8 months; 10 h in the older child. Those periods should be reduced if the child is ill (fever, reduced dietary intake ).

4) in case of surgery: administer glucose IV at a dose of 8 mg/kg/min up to 1 year; 7 mg/kg/min up to 3 years; 6.5 mg/kg/min up to 6 years; 5.5 mg/kg/min up to 14 years and 3-4 mg/kg/min in the adolescent or adult.

Anesthetic implications: 

avoid prolonged fasting: provide glucose (G10%: 4-5 mg/kg/min) supplementation as soon as the fasting begins and check blood glucose levels. The use of a continuous infusion of propofol is contraindicated but a single induction dose does not cause any problem (ideally with 2% propofol solution to minimize the lipidic load). Risk of rhabdomyolysis with succinylcholine ? Check muscle perfusion in situations at risk for muscle compression (tourniquet, compartment syndrome, surgical position). Given the fact that sevoflurane inhibits the oxidation of the fatty acids in an  animal model, some authors advocate for the use of remimazolam for induction and maintenance of anesthesia.

References : 

•        Feillet F, Ogier H, Aquaviva C, Labarthe F et al.  
  Déficit en acyl-CoA-déshydrogénase des acides gras à chaîne moyenne (MCAD) : consensus français pour le dépistage, le diagnostic, et la prise en charge.  
  Arch Pédiatr 2012 ; 19 : 184-93.

-         Wang SY, Kannan S, Shay D et al. 
Anesthetic considerations for a patient with compound heterozygous medium-chain Acyl-CoA dehydrogenase deficiency. 
Anesth Analg 20002 ; 94 : 1595-7.

-         Derks TG, van Spronsen FJ, Rake JP et al. 
Safe and unsafe duration of fasting for children with MCAD deficiency. 
Eur J Pediatr 2007; 166: 5-11.

-         Scrace B, Wilson P,  Pappachan J. 
Medium chain acyl CoA deshydrogenase deficiency causes unexplained coma in a 10-year-old child. 
Pediatr Anesth 2008; 18: 1230-1.

-         Justiz AC, Mayhew JF. 
Anesthesia in a child with medium-chain Acyl CoA dehydrogenase deficiency. 
Pediatr Anesth 2006; 16: 1293-4.

-        Allen C, Perkins R, Schwahn B.
A retrospective review of anesthesia and perioperative care in children with medium-chain acyl-CoA dehydrogenase deficiency.
Pediatr Anesth 2017; 27: 60-5

-        Prabhu SS, Doudnikoff AL, Mueller N, Reebye UN.
Anesthetic management for a patient with medium-chain-acyl CoA dehydrogenase deficiency in an outpatient setting using ketamine and fentanyl.
J Clin Anesth 2019 ; 56 : 45-6.

-        Kiyokawa M, Saito J, Nakai K, Hirota K.
Remimazolam and Remifentanil anesthetic for a pediatric patient with a Medium-Chain Acyl-CoA Dehydrogenase Deficiency: a case report.
A&A Practice 2022 ; 16 : e01646

Updated: January  2023