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.
Komlósi
K
K
Department of Medical Genetics and Child Development, University of Pécs, Szigeti út 12., H-7624, Pécs, Hungary.
Magyari
L
L
Talián
G C
GC
Nemes
E
E
Káposzta
R
R
Mogyorósy
G
G
Méhes
K
K
Melegh
B
B
D000328:Adult; D002331:Carnitine / Q000008:administration & dosage / Q000097:blood* / Q000172:deficiency; D016022:Case-Control Studies; D002675:Child, Preschool; D003241:Consanguinity; D016368:Frameshift Mutation; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000172:deficiency* / Q000235:genetics*; D000074058:Solute Carrier Family 22 Member 5; D021241:Spectrometry, Mass, Electrospray Ionization
D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D002331:Carnitine