[MIM 212 140]

(deficiency in carnitine carrier, CUD, PCD)

Carnitine is a small water-soluble molecule playing an essential role in the oxidation of fatty acids at the mitochondrial level and the elimination of the (toxic) acylcarnitine from the mitochondria. Carnitine is synthesized in small quantities at the level of the liver and kidneys, but an important part of its supply is exogenous from meat and dairy products. Human milk and "whey" contain carnitine, but soy preparations do not.

Primary or secondary carnitine deficiency are distinct:

• primary deficiencies: deficiency in carnitine carrier, carnitine-palmitoyl transferase I or II or acylcarnitine transferase
• secondary deficiencies:

a) many metabolic abnormalities result in a secondary carnitine deficiency: disorders of the ß-oxidation of fatty acids, urea cycle,  somemitochondrial cytopathies

b) preterm birth, cyclosporine or valproate therapy, parenteral nutrition without carnitine supplements

Carnitine carrier deficiency is very rare: incidence of 1/40,000 in Japan and 1/120,000 in Australia. Autosomal recessive transmission of a mutation of the SLC22A5 gene (in 5q23.3) coding for an organic cation carrier type 2 (OCTN2). It produces a dysfunction in cell carnitine uptake . The clinical manifestations vary depending on the age of the first symptoms, the affected organs and the severity of the signs:

-         discovery following systematic neonatal screening

-         sudden death or encephalopathy in the neonatal period

-         infantile metabolic form (50 %): metabolic decompensation between the age of 3 and 30 months: hypoketotic hypoglycemia, hyperammonemia, hepatomegaly, SGPT elevation, hepatic encephalopathy during fasting or an intercurrent infection (clinical picture of Reye's syndrome)

-         myopathic form of the child (50 %): between the age of 1 and 4 years: dilated cardiomyopathy with hypotonia, proximal myopathy with atrophy and high CPK levels

-         the adult form: minor symptoms: excessive fatigue; rarely: cardiac rhythm disorders or dilated cardiomyopathy

Diagnosis: very low plasmatic levels of free carnitine: < 5µM

Treatment: therapeutic supply of L-carnitine: 100 - 400 mg/kg/day in 3-4 doses. Carnitine supply is adapted according to resulting plasmatic levels (normal: 25-50 µM) because too high doses produce diarrhea and a fishy smell by production of trimethylamine.

Anesthetic implications: 

echocardiography and liver enzymes, CPK; avoid prolonged fasting, glucose should be added to perioperative IV infusions and blood glucose levels monitored. Principles of a mitochondrial cytopathy management. Avoid a continuous infusion of propofol: theoretically increased risk of "propofol infusion syndrome" (PRIS).

References : 

• Morris AAM, Spierkoetter U. 
  Disorders of mitochondrial fatty acid oxidation and related metabolic pathways, In Inborn metabolic diseases, Saudubray J-M, van den Berghe G, Walter JH. 5th edition, Springer 2011, p 201-16.
• Magoulas PL, El-Hattab AW. 
  Systemic primary carnitine deficiency: an overview of clinical manifestations, diagnosis, and management.
  Orphanet J Rare Diseases 2012; 7:68.
• Rowe RW, Helander E. 
  Anesthetic management of a patient with systemic carnitine deficiency. 
  Anesth Analg 1990; 71: 295-7.
• Kato K, Mizota T, Hirota K, Fukuda K. 
  Successful perioperative management of a patient with primary systemic carnitine deficiency: a case report. 
  J Anesth 2013; 27: 141-2.

Updated: September 2019