Natural history and outcome of nonketotic hyperglycinemia in China.

Introduction: Nonketotic hyperglycinemia (NKH) is a rare, life-threatening genetic disorder. The patients usually show heterogeneous and nonspecific symptoms, resulting in diagnosis challenges using conventional approaches. Here, the clinical presentation and genetic features of 20 Chinese patients were examined and reported in order to clarify the natural history and prognosis of NKH in China.

Clinical and genetic analysis of methylmalonic aciduria in 60 patients from Southern China: a single center retrospective study.

Background: Methylmalonic aciduria (MMA) is a group of rare genetic metabolic disorders resulting from defects in methylmalonyl coenzyme A mutase (MCM) or intracellular cobalamin (cbl) metabolism. MMA patients show diverse clinical and genetic features across different subtypes and populations.

Methods: We retrospectively recruited 60 MMA patients from a single center and diagnosed them based on their clinical manifestations and biochemical assays.

Mechanisms underlying the efficacy and limitation of dopa and tetrahydrobiopterin therapies for the deficiency of GTP cyclohydrolase 1 revealed in a novel mouse model.

Dopa and tetrahydrobiopterin (BH4) supplementation are recommended therapies for the dopa-responsive dystonia caused by GTP cyclohydrolase 1 (GCH1, also known as GTPCH) deficits. However, the efficacy and mechanisms of these therapies have not been intensively studied yet. In this study, we tested the efficacy of dopa and BH4 therapies by using a novel GTPCH deficiency mouse model, Gch1, which manifested infancy-onset motor deficits and growth retardation similar to the patients.

Severe Zellweger spectrum disorder due to a novel missense variant in the PEX13 gene: A case report and the literature review.

Background: Peroxisome biogenesis disorders (PBDs) are caused by variants in PEX genes that impair peroxisome function. Zellweger spectrum disorders (ZSDs) are the most severe and common subtype of PBDs, affecting multiple organ systems due to peroxisomal involvement in various metabolic functions. PEX13 gene variants are rare causes of ZSDs, with only 21 cases reported worldwide and none in China.

Features of liver injury in 138 Chinese patients with NICCD.

Objectives: To find biochemical and molecular markers can assist in identifying serious liver damage of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) patients.

Methods: 138 patients under 13 days to 1.1 year old diagnosed of NICCD in our center from 2004 to 2020.

A sensitive liquid chromatography-tandem mass spectrometry method for determination biomarkers of monoamine neurotransmitter disorders in cerebrospinal fluid.

Background: Cerebrospinal fluid (CSF) monoamine neurotransmitters, their precursors and metabolites are essential biomarkers in the diagnosis and follow-up of monoamine neurotransmitter disorders (MNDs). However, their extra low concentrations and potential instability challenge the detection method. Here, we present a method that enables simultaneous quantification of these biomarkers.

Diagnosis of an intermediate case of maple syrup urine disease: A case report.

Background: Maple syrup urine disease (MSUD) is an autosomal recessive genetic disorder caused by defects in the catabolism of the branched-chain amino acids (BCAAs). However, the clinical and metabolic screening is limited in identifying all MSUD patients, especially those patients with mild phenotypes or are asymptomatic. This study aims to share the diagnostic experience of an intermediate MSUD case who was missed by metabolic profiling but identified by genetic analysis.

Plasma Amino Acid Profile in Children with Autism Spectrum Disorder in Southern China: Analysis of 110 Cases.

To retrospectively explore the characteristics of plasma amino acids (PAAs) in children with autism spectrum disorder and their clinical association via case-control study. A total of 110 autistic and 55 healthy children were recruited from 2014 to 2018. The clinical phenotypes included severity of autism, cognition, adaptability, and regression.

Detection of glucosylsphingosine in dried blood spots for diagnosis of Gaucher disease by LC-MS/MS.

Introduction: Gaucher disease (GD) is caused by a deficiency of β-glucosidase (GCase), leading to accumulation of glucosylceramide (GlcC) and glucosylsphingosine (Lyso-Gb1). Lyso-Gb1 is a reliable biomarker for GD.

Objectives: This study aims to develop a simple, effective and accurate method for the screening and diagnosis of GD using dried blood spot (DBS) samples.

Simultaneous quantification of 48 plasma amino acids by liquid chromatography-tandem mass spectrometry to investigate urea cycle disorders.

Urea cycle disorders (UCD) are inborn errors of ammonia detoxification in which early diagnosis and treatment are critical to prevent metabolic emergencies. Unfortunately, the diagnosis was often and pronounced delayed. To improve diagnosis, we developed herein a liquid chromatography-tandem mass spectrometry method to investigate the disturbance of amino acid profile caused by UCD.

Rapid quantification of metabolic intermediates in blood by liquid chromatography-tandem mass spectrometry to investigate congenital lactic acidosis.

A novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been established to quantify metabolic intermediates, including lactate (Lac), pyruvate (Pyr), acetoacetate (ACAC) and 3-hydroxybutyrate (3-HB) in blood. Samples were deproteinized with methanol-acetonitrile solution, and analytes were separated on an adamantyl group-bonded reverse phase column and detected in multiple reaction monitoring mode. Total analysis time was 4 min per sample.

[Identification of a novel pathogenic mutation in PDHA1 gene for pyruvate dehydrogenase complex deficiency].

Objective: To study the molecular genetic mechanism and genetic diagnosis of pyruvate dehydrogenase complex deficiency (PHD), and to provide a basis for genetic counseling and prenatal genetic diagnosis of PHD.

Methods: Polymerase chain reaction (PCR) was performed to amplify the 11 exons and exon junction of the PDHA1 gene from a child who was diagnosed with PHD based on clinical characteristics and laboratory examination results. The PCR products were sequenced to determine the mutation.

Clinical, biochemical, neuroimaging and molecular findings of X-linked Adrenoleukodystrophy patients in South China.

X-linked adrenoleukodystrophy is a common X-linked recessive peroxisomal disorder caused by the mutations in the ABCD1 gene. In this study, we analyzed 19 male patients and 9 female carriers with X-linked adrenoleukodystrophy in South China. By sequencing the ABCD1 gene, 13 different mutations were identified, including 7 novel mutations, and 6 known mutations, and 1 reported polymorphism.

Calcium-sensing receptor stimulates Cl(-)- and SCFA-dependent but inhibits cAMP-dependent HCO3(-) secretion in colon.

Colonic bicarbonate (HCO3(-)) secretion is a well-established physiological process that is closely linked to overall fluid and electrolyte movement in the mammalian colon. These present studies show that extracellular calcium-sensing receptor (CaSR), a fundamental mechanism for sensing and regulating ionic and nutrient compositions of extracellular milieu in the small and large intestine, regulates HCO3(-) secretion. Basal and induced HCO3(-) secretory responses to CaSR agonists were determined by pH stat techniques used in conjunction with short-circuit current measurements in mucosa from rat distal colon mounted in Ussing chambers.

First case report of medium-chain acyl-coenzyme A dehydrogenase deficiency in China.

Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is an autosomal recessive inborn error of mitochondrial fatty acid β-oxidation, caused by mutations in the ACADM gene. As it is the most commonly inherited disorder of the mitochondrial fatty acid oxidation in Caucasians, there are no related reports in China diagnosed by molecular genetic testing. We report here the case of a 2-year-old female patient who had hepatomegaly and abnormal liver function with a common illness, and who had been healthy before.

Separation and identification of underivatized plasma acylcarnitine isomers using liquid chromatography-tandem mass spectrometry for the differential diagnosis of organic acidemias and fatty acid oxidation defects.

A simple HPLC-MS/MS method has been established to separate and identify underivatized acylcarnitine isomers. Human plasma samples were deproteinized and concentrated. Acylcarnitines were separated on a reverse phase column and detected with triple quadrupole linear ion trap mass spectrometry.

Measurement of free carnitine and acylcarnitines in plasma by HILIC-ESI-MS/MS without derivatization.

Measurement of carnitine and acylcarnitines in plasma is important in diagnosis of fatty acid β-oxidation disorders and organic acidemia. The usual method uses flow injection tandem mass spectrometry (FIA-MS/MS), which has limitations. A rapid and more accurate method was developed to be used for high-risk screening and diagnosis.

First case report of short-chain acyl-CoA dehydrogenase deficiency in China.

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare autosomal recessive inborn error of mitochondrial fatty acid oxidation. It is caused by rare mutations as well as polymorphic susceptibility variants. We describe here the case of a 1-year-old male patient who had growth and mental retardation, seizures, and recurring fever since infancy.

Evaluation of factors influencing accuracy in the analysis of succinylacetone in dried blood spots.

Background: Dried blood spots offer specific advantages over conventional blood collection methods, but with certain limitations. This article aims to evaluate factors which affect succinylacetone test in dried blood spots.

Methods: Whole blood with defined hematocrit and blood volume spiked with succinylacetone was spotted on filter paper, and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).