Unbalanced long-chain fatty acid beta-oxidation in newborns with cystic fibrosis and congenital hypothyroidism.

Background: Immediately after birth, adaptation to the extrauterine environment includes an upregulation of fatty acid catabolism. Cystic fibrosis and untreated hypothyroidism exert a life-long impact on fatty acid metabolism, but their influence during this transitional period is unknown. Children and adults with cystic fibrosis exhibit unbalanced fatty acid composition, most prominently a relative deficit of linoleic acid. Lipid catabolism is downregulated in hypothyroidism.

Methods: We analyzed acylcarnitine data in newborn screening blood spot samples from infants with cystic fibrosis, with congenital hypothyroidism, or without congenital disorders. Eight long-chain acylcarnitine species were quantified. Of primary interest was the relative composition of linoleoylcarnitine (C18:2), the acylcarnitine of linoleic acid. Mixed effects modeling was used to determine the impact of disease status on acylcarnitine levels, accounting for possible covariates including birth weight, gestational age, sex and race.

Results: Total long-chain acylcarnitine levels were diminished in newborns with cystic fibrosis and with congenital hypothyroidism. Contrary to expectations, C18:2 composition was elevated in newborns with cystic fibrosis and with congenital hypothyroidism, as compared to those without congenital disorders. Furthermore, higher thyroid-stimulating hormone levels, indicative of more severe hypothyroidism, predicted higher C18:2 composition.

Conclusions: Decreased total long-chain acylcarnitine concentrations in newborns with cystic fibrosis and congenital hypothyroidism suggest diminished beta-oxidation. However, the unexpected relative increase in C18:2 indicates selective preservation of linoleic acid beta-oxidation in both conditions. This is especially surprising in cystic fibrosis where linoleic acid levels become diminished and suggests that linoleic acid beta-oxidation contributes to the deficiency of linoleic acid in cystic fibrosis.