Plasma carnitine ester profile in homozygous and heterozygous OCTN2 deficiency.

The carnitine ester spectrum was studied using ESI tandem mass spectrometry in a 2.5-year-old male Roma child with homozygous deletion of 844C of the SLC22A5 gene, presenting with hepatopathy and cardiomyopathy. Besides the dramatic decrease of plasma free carnitine (1.38 vs 32.7 mumol/L in controls) all plasma carnitine esters were severely decreased in the proband: the total esters were 31.4% of the controls. In three heterozygous siblings the free carnitine level was 62.3% of the normal controls, while the levels of the individual carnitine esters ranged between 15.5% and 163% (average 70.9%). The heterozygous parents exhibited the same pattern. The proband was supplemented with 50 mg/kg per day of L-carnitine oral solution. After 2 months of treatment, his hepatomegaly, elevated transaminases and the pathological cardiac ultrasound parameters normalized. The plasma free carnitine rose to 12.8 mumol/L (39% of the controls). All of the carnitine esters also increased; however, the individual esters were still 8.5-169.7% of the controls (average 55.5%). After 13 months of treatment there was a further increase in free carnitine (15.9 mumol/L) as well as in the level of the individual esters, ranging between 16.1% and 140.3% of the controls (average 66.9%). The data presented here show that, besides the dramatic decrease of free carnitine, the carnitine ester metabolism is also affected in OCTN2 deficiency; the replenishment of the pools under treatment is slow. Despite an impressive clinical improvement, the carnitine metabolism can be still seriously affected.