11 children with either
cystinosis or Lowe's syndrome had a reduced content of plasma and muscle
carnitine due to
renal Fanconi syndrome.
After treatment with oral
L-carnitine, 100 mg/kg per d divided every 6 h, plasma
carnitine concentrations became normal in all subjects within 2 d. Initial plasma
free fatty acid concentrations, inversely related to free
carnitine concentrations, were reduced after 7-20 mo of
carnitine therapy. Muscle
lipid accumulation, which varied directly with duration of
carnitine deficiency (r = 0.73), improved significantly in three of seven rebiopsied patients after
carnitine therapy. One Lowe's syndrome patient achieved a normal muscle
carnitine level after
therapy. Muscle
carnitine levels remained low in all
cystinosis patients, even though cystinotic muscle cells in culture took up L-[3H]
carnitine normally. The half-life of plasma
carnitine for cystinotic children given a single oral dose approximated 6.3 h; 14% of ingested
L-carnitine was excreted within 24 h. Studies in a uremic patient with
cystinosis showed that her plasma
carnitine was in equilibrium with some larger compartment and may have been maintained by release of
carnitine from the muscle during dialysis. Because oral
L-carnitine corrects plasma
carnitine deficiency, lowers plasma
free fatty acid concentrations, and reverses muscle
lipid accumulation in some patients, its use as
therapy in
renal Fanconi syndrome should be considered. However, its efficacy in restoring muscle
carnitine to normal, and the optimal dosage regimen, have yet to be determined.