Mutational analysis for biotinidase deficiency of a Greek patients' cohort ascertained through expanded newborn screening.

Late-onset multiple carboxylase deficiency, also known as biotinidase (BTD) deficiency, is an autosomal recessively inherited disorder of biotin metabolism. Its early diagnosis and treatment seems that it can even fully prevent its various clinical manifestations. Mutations in the BTD gene scattered throughout its coding region have been detected in patients ascertained either through newborn screening or clinically. From March 2010 up to June 2011, 18 954 Greek neonates were subjected to biochemical determination of BTD activity through a semiquantitative fluoroimmunoassay. Subsequently, the first cohort of our 'suspected' samples was further tested for the presence of aberrations associated either with partial or profound BTD deficiency through sequencing of the coding region of the BTD gene, including splice-site junctions. On the basis of the molecular data derived from the study of our first cohort of 'suspected' samples, a panel of four mutations, most frequently encountered in the Greek population, was created, and a rapid, reliable and cost-effective real-time-based genotyping assay for the detection of these mutations was developed. This is the first report about the BTD mutational spectrum in Greece, and it could be a beneficial utility in the differential clinical diagnosis of BTD deficiency.

Parenteral MCT/ω-3 Polyunsaturated Fatty Acid-Enriched Intravenous Fat Emulsion Is Associated With Cytokine and Fatty Acid Profiles Consistent With Attenuated Inflammatory Response in Preterm Neonates: A Randomized, Double-Blind Clinical Trial.

BACKGROUND: Soybean oil-based intravenous fat emulsion (IVFE) administered to preterm neonates can induce oxidative stress and inflammatory response, which are associated with severe complications of prematurity. This study aimed to test the hypothesis that administration of medium-chain triglyceride (MCT)/ω-3 polyunsaturated fatty acid (PUFA)-enriched IVFE in preterm neonates is associated with a cytokine and fatty acid (FA) profile consistent with attenuated inflammatory response. PATIENTS/METHODS: In a double-blind randomized study, 60 preterm neonates (gestational age 26-32 weeks) were randomized to receive either MCT/ω-3 PUFA-enriched IVFE (intervention group) or soybean oil-based IVFE (control group). Serum biochemistry, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, α-tocopherol, and FAs were assessed at baseline, on day of life 15, and day of life 30 or at the end of intervention. RESULTS: All cytokine levels changed significantly across the 3 time points, whereas the type of IVFE had a significant effect on final IL-6 and IL-8 levels, which were lower in the intervention group. The difference in final IL-6 and IL-8 levels remained significant after controlling for bronchopulmonary dysplasia and/or infection. α-Tocopherol and FA values changed significantly over time. MCT/ω-3 PUFA-enriched IVFE administration was associated with significantly higher α-tocopherol, eicosapentaenoic acid, docosahexaenoic acid, and ω-3 PUFAs and lower linolenic acid, total PUFA, and ω-6/ω-3 PUFA values compared with soybean oil-based IVFE. Both IVFEs were well tolerated. CONCLUSION: Compared with the soybean oil-based IVFE, the MCT/ω-3 PUFA-enriched IVFE is associated with a more favorable cytokine and FA profile consistent with attenuated inflammatory response in preterm neonates.

Cholestasis, bronchopulmonary dysplasia, and lipid profile in preterm infants receiving MCT/ω-3-PUFA-containing or soybean-based lipid emulsions.

BACKGROUND: This study aimed to compare the effect of 2 lipid emulsions (LEs), a medium-chain triglyceride (MCT)/ω-3-polyunsaturated fatty acid (PUFA)-containing LE and a soybean-based LE, on the incidence of neonatal cholestasis, bronchopulmonary dysplasia (BPD), and lipid profile of preterm infants. Patients and METHODS: In this prospective, observational study, 2 groups of preterm neonates, the very low birth weight (VLBW) (n = 129) and the low birth weight (LBW) groups (n = 153), which received parenteral LEs for at least 7 days, were included. Infants received either MCT/ω-3-PUFA-containing LE (SMOFlipid, subgroup I) or soybean-based LE (Intralipid, subgroup II) according to the attending neonatologist's preference and availability. Full biochemical assessment was performed on days of life 15, 30, and 45 and on discharge. RESULTS: Of the VLBW infants, 7.4% and 13.3% of infants in subgroups I and II, respectively, developed cholestasis (P = .39; odds ratio [OR], 0.52; 95% confidence interval [CI], 0.15-1.76). The duration of LE administration was independently associated with cholestasis (P < .001; OR, 0.925; 95% CI, 0.888-0.963). The maximum amounts of lipids administered ranged between 1.6 and 3.6 g/kg/d in both VLBW subgroups. The VLBW subgroup I had lower incidence of BPD, lower alkaline phosphatase and phosphate, higher high-density lipoprotein (HDL), and lower cholesterol-to-HDL ratio on discharge than the VLBW subgroup II. The type of LE was independently associated with BPD and alkaline phosphatase. In the LBW group, the type of LE was not associated with clinical and biochemical parameters. CONCLUSION: In VLBW infants, the MCT/ω-3-PUFA-containing LE administration is associated with decreased BPD and more favorable lipoprotein profile. Although a trend toward a lower incidence of cholestasis was observed, a preventive effect of MCT/ω-3-PUFA-containing LE on parenteral nutrition-associated cholestasis is not supported.