Purpose: Primary carnitine deficiency is an autosomal recessive disorder of
fatty acid oxidation resulting from defective carnitine transport. This di
sease is caused by mutations in the carnitine transporter gene SLC22A5. The
objective of this study was to extend mutational analysis to four addition
al families with this disorder and determine whether recurrent mutations co
uld be found. Methods: The SLC22A5 gene encoding the OCTN2 carnitine transp
orter was sequenced, and the missense mutations identified were expressed i
n Chinese hamster ovary (CHO) cells. Results: DNA sequencing revealed four
novel mutations (Y4X; dup 254-264, 133X; R19P; R399Q). Alleles introducing
premature STOP codons reduced the levels of OCTN2 mRNA. Carnitine transport
in CHO cells expressing the R19P and R399Q mutations was reduced to <5% of
normal. The 133X mutation was found in two unrelated European families. Tw
o patients within the same family, both homozygous for the same mutation (R
399Q) had completely different clinical presentation. Conclusions: Heteroge
neous mutations in the SLC22A5 gene cause primary carnitine deficiency. Dif
ferent presentations are observed even in children with identical mutations
.