Accuracy of equations for estimating resting energy expenditure in children and adolescents living with phenylketonuria.

BACKGROUND: Measuring resting energy expenditure (REE) in individuals living with phenylketonuria (PKU) using indirect calorimetry (IC) is unusual in healthcare facilities because it requires specific protocols and expensive equipment. Considering that determining REE is crucial for devising nutritional strategies for the management of PKU, the aim of this study was to identify the predictive equations that provide the best estimates of REE in children and adolescents living with PKU and to propose a predictive equation for determining REE in this population. METHODS: An REE concordance study was conducted with children and adolescents living with PKU. Anthropometric and body composition assessments using bioimpedance and REE assessment using IC were performed. The results were compared to 29 predictive equations. RESULTS: Fifty-four children and adolescents were evaluated. The REE obtained using IC differed from all estimated REE, except Henry's equation for male children (p = 0.058). Only this equation showed good agreement (0.900) with IC. Eight variables were associated with the REE obtained using IC with emphasis on fat-free mass (kg) (r = 0.786), weight (r = 0.775), height (r = 0.759) and blood phenylalanine (r = 0.503). With these variables, three REE equations were suggested, with R2 = 0.660, 0.635 and 0.618, respectively, and the third equation, which involves weight and height, showed adequate sample size for a statistical power of 0.942. CONCLUSION: Most equations, not specific for individuals living with PKU, overestimate the REE of this population. We propose a predictive equation for assessing REE for children and adolescents living with PKU to be used in settings where IC is not available.

Fenretinide corrects newly found ceramide deficiency in cystic fibrosis.

Chronic and persistent lung infections cause the majority of morbidity and mortality in patients with cystic fibrosis (CF). Galactosyl ceramide has been previously shown to be involved in Pseudomonas internalization. Therefore, we assessed ceramide levels in the plasma of patients with CF and compared them to healthy volunteers using high-performance liquid chromatography followed by mass spectrometry. Our results demonstrate that patients with CF display significantly lower levels of several ceramide sphingolipid species, specifically C14:0, C20:1, C22:0, C22:1, and C24:0 ceramides, and dihydroxy ceramide (DHC16:0). We report that Cftr-knockout mice display diminished ceramide levels in CF-related organs (lung, pancreas, ileum, and plasma) compared with their littermate controls. Since it has been previously reported that in vitro treatment with fenretinide induced ceramide in neuroblastoma cell lines, we decided to test this drug in vivo using our Cftr-knockout mice in an attempt to correct this newly identified defect in ceramide levels. We demonstrate that treatment with fenretinide is able to increase ceramide concentrations in CF-related organs. We further assessed the biological effect of fenretinide on the ability of Cftr-knockout mice to combat lung infection with P. aeruginosa. Our data show dramatic improvement in the ability of Cftr-knockout mice to control P. aeruginosa infection. Overall, these findings not only document a novel deficiency in several ceramide species in patients with CF, but also demonstrate a pharmacologic means to correct this defect in Cftr-knockout mice. Our data provide a strong rationale for clinical intervention that may benefit patients with CF suffering from CF lung disease.