Coupling bootstrap with synergy self-organizing map-based orthogonal partial least squares discriminant analysis: Stable metabolic biomarker selection for inherited metabolic diseases.

Biomarker selection has played an increasingly important part in modern medicine with advances of omics techniques. Kohonen self-organizing map is a well-established variable reduction algorithm in identifying significant biomarkers based on variable clustering. However, high dimensionality but small sample size of omics data makes self-organizing map-based model problematic in terms of selection stability and reproducibility.

Identification and analyzes of DUOX2 mutations in two familial congenital hypothyroidism cases.

Background: Mutations in DUOX2 are the frequent cause of congenital hypothyroidism (CH), a common neonatal metabolic disorder characterized by great phenotypic variability. CH can be traditionally subclassified into two subtypes: thyroid dysgenesis (TD) and thyroid dyshormonogenesis. The objectives of this study were to analyze the genetic data of two familial CH cases, to elucidate the pathogenesis from the perspective of genetics and to review and summarize the previous findings.

A Nested Asymmetric PCR Melting Curve Assay for One-Step Genotyping of Nondeletional α-Thalassemia Mutations.

A rapid DNA-based assay is essential for clinical diagnosis and mass screening in thalassemia-prevention programs. Because of high homology and guanine-cytosine-rich and complex second structure of α-globin genes, it is rather difficult to develop a feasible and simple method for α-thalassemia genotyping. In this study, a strategy of nested asymmetric PCR melting curve analysis was designed to tackle these factors and ensure sensitivity and accuracy.

Clinical and genetic analysis of five Chinese patients with urea cycle disorders.

Background: The urea cycle plays a key role in preventing the accumulation of toxic nitrogenous waste products, including two essential enzymes: ornithine transcarbamylase (OTC) and argininosuccinate lyase (ASL). Ornithine transcarbamylase deficiency (OTCD) results from mutations in the OTC. Meanwhile, argininosuccinate lyase deficiency (ASLD) is caused by mutations in the ASL.

Chinese expert brief consensus on newborn screening of inherited metabolic disorders during the novel coronavirus infection epidemic.

Novel coronavirus (2019-nCov) infection (COVID-19) rapidly spread across China and 25 countries in the worldwide, which infected not only adults but also children, even neonates. Each year, about 15 million newborns are delivered in China. Newborn screening (NBS) helps effectively prevent some mental retardation, premature death, and adverse outcomes in the early stage of baby, which could detect some inherited metabolic disorders (IMDs).

Evaluation of a panel of very long-chain lysophosphatidylcholines and acylcarnitines for screening of X-linked adrenoleukodystrophy in China.

Background: Elevated blood C24:0- and C26:0-carnitines and lysophosphatidylcholines (LPCs) were reported as diagnostic biomarkers for X-linked adrenoleukodystrophy (X-ALD). Our aim was to establish the reference intervals of very long-chain (VLC) acylcarnitines (C20-C26) and LPCs in Chinese population, and evaluate valuable biomarkers and develop panel for screening X-ALD in China.

Methods: The method of FIA-MS/MS-based quantification of VLC acylcarnitines and LPCs was validated in order to determine their concentrations in dried blood spots from 7 X-ALD boys, 396 age-matched healthy controls, and 3078 putative normal newborns.

The Impact of Preconceptional Serum TSH Levels between 2.5 and 4.0 mIU/L on Infertile Women Going through Their First IUI Treatment Cycle.

Objective: To evaluate the impact of preconceptional serum TSH levels on the clinical outcomes of infertile patients undergoing their first IUI treatment cycle.

Method: This was a retrospective study. Euthyroid patients undergoing the first cycle of IUI treatment from Jan 2017 to Aug 2018 were included.

[Screening for hereditary tyrosinemia and genotype analysis in newborns].

Objective: To analyze the results of screening for hereditary tyrosinemia (HT) in newborns and its clinical features and genotype.

Methods: The HT screening was conducted among 2 188 784 newborns from November 2013 to November 2018. The tyrosine (TYR)/ succinylacetone (SA) levels were detected by tandem mass spectrometry (MS-MS).

[Genetic analysis of newborns with abnormal metabolism of 3-hydroxyisovalerylcarnitine].

Objective: To investigate the genetic characterization of 3-hydroxyisovalerylcarnitine (C5-OH) metabolic abnormality in neonates.

Methods: Fifty two newborns with increased C5-OH, C5-OH/C3 and C5-OH/C8 detected by tandem mass spectrometry during neonatal screening were enrolled in the study. Genomic DNA was extracted from the whole blood samples of 52 cases and their parents.

Congenital Nonspherocytic Hemolytic Anemia Caused by Gene Variants: Another Case Report.

In this study, we report on a compound heterozygote for variants in the key erythroid transcription factor () gene in a patient who presented with severe, transfusion-dependent hemolytic anemia. The red cells were normochromic and normocytic, and resembled those seen in patients with congenital nonspherocytic hemolytic anemia (CNSHA). Next generation sequencing (NGS) revealed that the patient was a compound heterozygote for the frameshift variant c.

Prognostic significance of CXCR4 expression in acute myeloid leukemia.

Background: CXCR4 chemokine receptors play an important role in leukemia proliferation, extramedullary migration, infiltration, adhesion, and resistance to chemotherapy drugs.

Methods: The CXCR4 expression by flow cytometry in 122 acute myeloid leukemia (AML) patients between 2010 and 2014 was analyzed.

Results: The expression of CXCR4 in AML-M4/M5 was found to be significantly higher than that of other subtypes according to both FAB subtype and WHO classification.

Chinese newborn screening for the incidence of G6PD deficiency and variant of G6PD gene from 2013 to 2017.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common X-linked enzymopathies caused by G6PD gene variant. We aimed to provide the characteristics of G6PD deficiency and G6PD gene variant distribution in a large Chinese newborn screening population. We investigated the prevalence of G6PD in China from 2013 to 2017.

Very rare condition of multiple Gaucheroma: A case report and review of the literature.

Background: This study presented a 3 years old boy with Gaucher disease (GD) who was treated with enzyme replacement therapy(ERT) for 19 months and developed multiple Gaucheroma. The literature was reviewed.

Methods: The medical chart and literature were reviewed.

Novel mutations in two unrelated Italian patients with SSADH deficiency.

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive disorder of γ-aminobutyric acid (GABA) catabolism caused by mutations in the gene coding for succinic semialdehyde dehydrogenase (ALDH5A1). The abnormal levels of GHB detected in the brain and in all physiological fluids of SSADHD patients represent a diagnostic biochemical hallmark of the disease. Here we report on the clinical and molecular characterization of two unrelated Italian patients and the identification of two novel mutations: a 22 bp DNA duplication in exon 1, c.

Very rare condition of multiple Gaucheroma: A case report and review of the literature.

Background: This study presented a 3 years old boy with Gaucher disease (GD) who was treated with enzyme replacement therapy (ERT) for 19 months and then developed multiple Gaucheroma. Review of literature was performed simultaneously.

Methods: The medical chart and literature were reviewed.

A verification of the application of the non-derivatized mass spectrometry method in newborns screening of metabolic disorders.

It is required that the clinical screening of metabolic disorders in newborns meet International Organization for Standardization 15189-2012 approval. The new tandem mass spectrometry (MS/MS) based screening system and its companion reagent should be independently authenticated before their implementation in clinical diagnosis laboratories.Linearity, stability, accuracy, and precision evaluations were carried out to verify the performance of the Waters ACQUITY TQD MS/MS system with the NeoBase non-derivatized MS/MS PerkinElmer kit for detecting amino acids and acylcarnitine in newborns with metabolic disorders.

Optimization and application of a dried blood spot-based genetic screening method for thalassemia in Shenzhen newborns.

Background: To optimize and apply an approach suitable for large-scale neonatal thalassemia genetic screening in China, thalassemia genotypes were determined by polymerase chain reaction-reverse dot blot using DNA extracted from dried blood spots (DBS) obtained from newborn screening programs.

Methods: Firstly, the most suitable commercial DNA extraction kit for DBS was screened. Then, the appropriate amount of DBS required for the automated high-throughput DNA extraction system was evaluated.

Applying a multiplexed primer extension method on dried blood spots increased the detection of carriers at risk of glucose-6-phosphate dehydrogenase deficiency in newborn screening program.

Background: Patients with glucose-6-phosphate dehydrogenase deficiency might develop acute hemolytic anemia, chronic hemolytic anemia, and neonatal hyperbilirubinemia when exposed to high levels of oxidative stress. Severe hemolysis may occur in not only patients but also female carriers under certain conditions. However, 80%-85% of female carriers were undetected in an existing newborn screening program because of their wide-ranging levels of enzyme activity.

Osthole inhibits proliferation and induces apoptosis in BV-2 microglia cells in kainic acid-induced epilepsy via modulating PI3K/AKt/mTOR signalling way.

Context: Osthole is a natural coumarin compound most frequently extracted from plants of the Apiaceae family such as Cnidium monnieri (L.) Cusson, Angelica pubescens Maxin.f.

Taiwan National Newborn Screening Program by Tandem Mass Spectrometry for Mucopolysaccharidoses Types I, II, and VI.

Objective: To evaluate the initial cutoff values, rates of screen positives, and genotypes for the large-scale newborn screening program for multiple mucopolysaccharidoses (MPS) in Taiwan.

Study Design: More than 100 000 dried blood spots were collected consecutively as part of the national Taiwan newborn screening programs. Enzyme activities were measured by tandem mass spectrometry from dried blood spot punches.

[Analysis of GCDH gene mutations in 3 patients from Fujian area with glutaric academia type I].

Objective: To explore clinical features and mutation types in patients from Fujian area with glutaric academia type I(GA I).

Methods: Serum acylcarnitine and urine organic acid of 3 patients were determined with tandem mass spectrometry and gas chromatographic mass spectrometry. The patients also underwent magnetic resonance imaging analysis for the cranial region.