Mutational spectrum of phenylketonuria in Jiangsu province.

UNLABELLED: Phenylketonuria (PKU) is caused by variants in the phenylalanine hydroxylase (PAH) gene. We systematically investigated all 13 exons of the PAH gene and their flanking introns in 31 unrelated patients and their parents using next-generation sequencing (NGS). A total of 33 different variants were identified in 58 of 62 mutant PAH alleles. The prevalent variants with a relative frequency of 5 % or more were c.721C > T, c.1068C > A, c.611A > G, c.1197A > T, c.728G > A, c.331C > T, and c.442-1G > A. One novel variant was identified in this study-c.699C > G. We studied genotype-phenotype correlations using the Guldberg arbitrary value (AV) system, which revealed a consistency rate of 38 % (8/21) among the 21 predicted phenotypes. The genotype-based prediction of BH4 responsiveness was also evaluated, and 14 patients (45.2 %) were predicted to be BH4 responsive. CONCLUSION: This study presents the spectrum of PAH variants in Jiangsu province. The information obtained from the genotype-based prediction of BH4 responsiveness might be used for the rational selection of candidates for BH4 testing. WHAT IS KNOWN: • Phenylketonuria (PKU) is caused by variants in the phenylalanine hydroxylase (PAH) gene. • The spectrum of PAH variants in different Chinese populations has been reported. What is new: • This is the first report on the spectrum of PAH variants in Jiangsu province. • This study identified one novel PAH variant-c.699C>G-and and tries to show a genotype-phenotype relationship also regarding BH4-responsiveness.

Significance of low serum vitamin D for infection risk, disease severity and mortality in critically ill patients.

BACKGROUND: Hospitalized patients often have higher rate of vitamin D deficiency than healthy people. Vitamin D levels below normal are associated with hospital stay, increased incidence of adverse prognosis and increased mortality of a number of diseases. Whether there is a relationship between vitamin D levels and infection or sepsis in the critically ill is still unclear. This study will explore the relationship between vitamin D levels and risk of infection, assessment for disease severity, and predictor of mortality. METHODS: To evaluate the value of vitamin D in intensive care unit (ICU) cases to sepsis, severity and prognosis assessment, high performance liquid chromatography and tandem mass spectrometry were used to measure the concentrations of vitamin D in sera of critically ill patients. The serum samples were drawn within the first 24 hours of ICU admission. RESULTS: The study included 206 people, 50 healthy controls, 51 ICU control patients and 105 ICU diagnosed with sepsis. Critically ill ICU patients (ICU sepsis and ICU control group) had lower vitamin D concentration than normal people, but septic patients showed no significant reduction of vitamin D concentration when compared with critically ill patients with no positive etiological evidence. For assessment of disease severity, there were very low negative correlations between APACHE II, SAPS II and SOFA scores and vitamin D level. Additionally, patients of different 25-(OH)D levels showed no difference whether in terms of 28-day survival (X(2) = 1.78, P = 0.776) or 90-day survival (X(2) = 4.12, P = 0.389). Multivariate Logistic regression demonstrated that APECHE II and SAPS II scores were independent risk factors to deaths caused by sepsis. CONCLUSION: Clinically, serum concentration of vitamin D is not an indicator for diagnosis and assessment in critically ill patients (ClinicalTrial.gov identifier NCT01636232).