Inadequate iron availability as a possible cause of low serum carnitine concentrations in patients with phenylketonuria.

A previous observation of decreased serum carnitine concentrations in phenylketonuria (PKU) was investigated in 169 patients either on a strict diet (n = 107; median: 8.1 years) or off diet (n = 62; median: 15.0 years). Fifty-seven metabolically healthy children (median: 8.5 years) served as controls. PKU patients on a strict diet and older than 2 years had significantly lower serum carnitine concentrations (19.4 +/- 5.4 mumol/l) than those off diet (29.6 +/- 6.7 mumol/l). PKU patients on diet also had significantly lower concentrations of haemoglobin and serum ferritin than those off diet. A linear correlation existed between total serum carnitine and ferritin concentrations up to 40 micrograms/l (r = 0.52; P less than 0.01). As iron is an essential cofactor of carnitine synthesis we conclude that reduced endogenous carnitine synthesis due to an inadequate availability of iron may be a major cause of low serum carnitine concentrations. The low carnitine content of the strict and highly protein-reduced diet additionally contributes to a decrease in the serum carnitine concentration. Our results show that a further optimization of the PKU diet increasing either iron availability or carnitine intake should be considered.