Sepsis is one of the most important problems to be addressed in pediatrics, characterized by insidious onset, rapid progression, and high rates of severe infection and even mortality. Biomarkers with high sensitivity and robustness are urgently required for the early diagnosis of infant sepsis. Serum metabolomic approaches based on liquid chromatography-mass spectrometry were used to analyze the samples from 30 infants with sepsis at an early stage and 30 infants with noninfectious diseases. Multivariate statistical analysis was used to screen for differential metabolites and ROC curves were generated to find potential biomarkers. Six metabolites, including phosphatidic acid (PA (8:0/14:0)), phosphatidyl ethanolamine (PE (16:0/18:2(9Z,12Z))), cytidine 5'-diphosphocholine (CDP-CHO), sphingomyelin (SM (d18:0/16:1(9Z))), prolylhydroxyproline and phosphorylcholine (P-CHO), were identified between the two groups. ROC curve analysis showed that prolylhydroxyproline (AUC = 0.832) had potential diagnostic values for infant sepsis. The AUC value was 0.859 (CI: 0.764, 0.954) in the combined model. Prolylhydroxyproline were found to be correlated with CRP and PCT levels, while PE and CDP-CHO associated with PCT levels. Pathway analysis indicated that glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis and necroptosis pathways played important roles in infant sepsis. Network analysis showed that the differential metabolites were linked to ERK/ MAPK, NF-κB, AMPK, mTOR, and other classical inflammatory and metabolic signaling pathways. This study identified serum metabolite profiles and three metabolites as potential biomarkers in infants with sepsis. The findings will help improve the early diagnosis of sepsis in infants.

Osteopetrosis is a genetic condition of the skeleton characterized by increased bone density caused by osteoclast formation and function defects. Osteopetrosis is inherited in the form of autosomal dominant and autosomal recessive manner. We report autosomal recessive osteopetrosis (ARO; OMIM 611490) in a Chinese case with a history of scarce leukocytosis, vision and hearing loss, frequent seizures, and severe intellectual and motor disability. Whole-exome sequencing (WES) followed by Sanger sequencing revealed novel compound heterozygous mutations in the chloride channel 7 (CLCN7) gene [c.982-1G > C and c.1208G > A (p. Arg403Gln)] in the affected individual, and subsequent familial segregation showed that each parent had transmitted a mutation. Our results confirmed that mutations in the CLCN7 gene caused ARO in a Chinese family. Additionally, our study expanded the clinical and allelic spectrum of the CLCN7 gene and enhanced the applications of WES technology in determining the etiology of prenatal diagnoses in fetuses with ultrasound anomalies.

Background: Sepsis is one of the most important problems to be addressed in pediatrics, characterized by insidious onset, rapid progression, and high rates of severe infection and even mortality. There is an urgent clinical need for sensitive and robust biomarkers to assist in the early diagnosis of infant sepsis.Methods: We used serum metabonomics approach based on liquid chromatography-mass spectrometry to analyze the samples from 30 infants with sepsis at an early stage and 30 infants with noninfectious diseases. Multivariate statistical analysis was used to screen for differential metabolites and receiver operating characteristic (ROC) curves were generated to find potential biomarkers. Subsequently, the relationship between potential biomarkers and classical infection indicators (CRP and PCT) was analyzed with Spearman's correlation coefficient. Lastly, metabolic pathway analysis was performed to explore the metabolic and signaling pathways associated with the differential metabolites.Results: Seven lipid metabolites (phosphatidic acid (PA), phosphatidyl ethanolamine (PE (16:0/18:2(9Z,12Z))), cytidine 5'-diphosphocholine (CDP-CHO), pubescenol, sphingomyelin (SM (d18:0/16:1(9Z))), prolylhydroxyproline and phosphorylcholine(P-CHO)) significantly different were identified between the sepsis group and control group. ROC curve analysis showed that pubescenol (Area Under the Curve (AUC) = 0.814) and prolylhydroxyproline (AUC = 0.832) have potential diagnostic values for infant sepsis. The AUC value of the diagnostic model constructed using the two biomarkers was 0.888 (CI: 0.807, 0.969). Pubescenol, PE and prolylhydroxyproline were found to be correlated with CRP and PCT levels, and CDP-CHO with PCT levels. Pathway analysis indicated that glycerophospholipid metabolism and phenylalanine, tyrosine, and tryptophan biosynthetic pathways played important roles in infant sepsis. Network analysis showed that these differential metabolites were associated with extracellular signal-regulated kinase/mitogen-activated protein kinase, nuclear factor-κB, AMP-activated protein kinase, mammalian target of rapamycin, and other classical inflammatory and metabolic signaling pathways. Conclusion: This study identified serum metabolite profiles and potential lipid biomarkers in infants with sepsis. These findings will help improve the early diagnosis of sepsis in infants.