Humans ; Liver Diseases ; complications ; diagnosis ; Metabolic Syndrome ; complications ; diagnosis

Bone Diseases, Metabolic ; diagnosis ; etiology ; therapy ; Chronic Disease ; Humans ; Liver Diseases ; complications ; diagnosis ; therapy

Child ; Female ; Forecasting ; Humans ; Mass Screening ; Metabolic Diseases ; diagnosis ; etiology ; Pediatrics ; trends ; Pregnancy ; Prenatal Diagnosis

PURPOSE: We developed a new workflow design which included results from both biochemical and targeted gene sequencing analysis interpreted comprehensively. We then conducted a pilot study to evaluate the benefit of this new approach in newborn screening (NBS) and demonstrated the efficiency of this workflow in detecting causative genetic variants. MATERIALS AND METHODS: Ten patients in Group 1 were diagnosed clinically using biochemical assays only, and 10 newborns in Group 2 were diagnosed with suspected inherited metabolic disease (IMD) in NBS. We applied NewbornDiscovery (SD Genomics), an integrated workflow design that encompasses analyte-phenotype-gene, single nucleotide variant/small insertion and deletion/copy number variation analyses along with clinical interpretation of genetic variants related to each participant's condition. RESULTS: A molecular genetic diagnosis was established in 95% (19/20) of individuals. In Group 1, 13 and 7 of 20 alleles were classified as pathogenic and likely pathogenic, respectively. In Group 2, 11 and 6 of 17 alleles with identified causative variants were pathogenic and likely pathogenic, respectively. There were no variants of uncertain significance. For each individual, the NewbornDiscovery and biochemical analysis results reached 100% concordance, since the single newborn testing negative for causative genetic variant in Group 2 showed a benign clinical course. CONCLUSION: This integrated diagnostic workflow resulted in a high yield. This approach not only enabled early confirmation of specific IMD, but also detected conditions not included in the current NBS.
Alleles ; Diagnosis ; Diagnosis, Differential* ; Humans ; Infant, Newborn* ; Mass Screening* ; Metabolic Diseases* ; Molecular Biology ; Pilot Projects

INTRODUCTIONRadiologists may encounter bilaterally symmetrical abnormalities of the basal ganglia on magnetic resonance imaging (MRI), typically in the context of diffuse systemic, toxic or metabolic diseases. A systematic approach and broad knowledge of pathology causing this uncommon group of conditions would be useful.

MATERIALS AND METHODSThis review uses illustrative images to highlight metabolic conditions, such as Leigh's syndrome, citrullinaemia, hypoglycaemia or carbon monoxide poisoning, as well as other causes of bilateral basal ganglia lesions such as osmotic myelinolysis, deep cerebral venous thrombosis and Creutzfeldt-Jakob disease.

RESULTSCareful assessment of radiological findings outside the basal ganglia, such as involvement of the cortex, white matter, thalamus and pons, together with clinical correlation, may be helpful in narrowing the differential diagnosis, and directing further radiological, biochemical or genetic investigations. Recent advances in MR technology have resulted in newer techniques including diffusion-weighted (DW) MR imaging and MR spectroscopy (MRS); these may be helpful if appropriately used.

CONCLUSIONSAbnormal MRI findings in the basal ganglia should not be interpreted in isolation. A systematic approach including DW MR imaging, MRS, and a broad knowledge of diffuse systemic, toxic or metabolic diseases is helpful.

Basal Ganglia Diseases ; diagnosis ; diagnostic imaging ; physiopathology ; Brain Diseases, Metabolic ; diagnosis ; diagnostic imaging ; Diagnosis, Differential ; Humans ; Magnetic Resonance Imaging ; Radiography

Follow-up is a crucial step for the screening of neonatal genetic and metabolic diseases, which can directly influence the detection, diagnosis, efficacy of treatment, as well as the quality of neonatal screening. In view of the lack of follow-up, full understanding, and inconsistent requirement between various agencies and personnel in China, there is an urgent need for standardization. The Committee for Proficiency Testing of the Neonatal Genetic Metabolic Disease Screening Center of the National Health Committee of China has organized the writing of expert consensus for follow-up of neonatal genetic and metabolic disease screening after thorough discussion, so as to guide the follow-up work and improve its quality.
China ; Consensus ; Follow-Up Studies ; Genetic Diseases, Inborn ; diagnosis ; Humans ; Infant, Newborn ; Metabolic Diseases ; diagnosis ; genetics ; Neonatal Screening

Microvesicles (MVs, also known as microparticles) are small vesicles that originate from plasma membrane of almost all eukaryotic cells during apoptosis or activation. MVs can serve as extracellular vehicles to transport bioactive molecules from their parental cells to recipient target cells, thereby serving as novel mediators for intercellular communication. Importantly, more and more evidence indicates that MVs could play important roles in early pathogenesis and subsequent progression of cardiovascular and metabolic diseases. Elevated plasma concentrations of MVs, originating from red blood cells, leukocytes, platelets, or other organs and tissues, have been reported in various cardiometabolic diseases. Circulating MVs could serve as potential biomarkers for disease diagnosis or therapeutic monitoring. In this review, we summarized recently-published studies in the field and discussed the role of MVs in the pathogenesis of cardiometabolic diseases. The emerging values of MVs that serve as biomarker for non-invasive diagnosis and prognosis, as well as their roles as novel therapeutic targets in cardiometabolic diseases, were also described.
Biomarkers ; metabolism ; Cardiovascular Diseases ; blood ; diagnosis ; therapy ; Cell Communication ; Cell-Derived Microparticles ; metabolism ; Humans ; Metabolic Diseases ; blood ; diagnosis ; therapy

OBJECTIVE: To evaluate the concordance, or discordance, of the osteoporotic diagnosis between femur neck and lumbar spine, using DEXA T-scores and the WHO classification. MATERIALS AND METHODS: The BMD (Define?) on both hips and of the lumbar spine of 718 Korean females were measured. The mean age of the subjects was 55.5 years (31-91). The BMD data were obtained from 3 hip regions and from the lumbar spine, anteroposteriorly, using dual-energy x-ray absorptiometry (Lunar). The BMDs of femur neck and the L2-4 vertebrae were classified into normal (a T-score >-1), osteopenia (-1 < or = T-score < -2.5) and osteoporosis (-2.5< or =T-score) using the WHO definitions. RESULTS: There was significant correlation between the femur neck and lumbar BMDs (r=0.772). However, the discordance rate was 33% for all the cases, but this was 20% in the subjects below 50 of age, 31% in the subjects in their 50's, 47% in their 60's and 42% when 70 or above. The discordance rates of the normal, osteopenic and osteoporotic groups were 21, 54 and 17% respectively, with the highest discordance rate in the osteopenia group. Among the 649 persons in the normal or osteopenia groups, in relation to the femur neck BMD, there were 67 (10.3%) in the osteoporotic group with L2-4 BMD. But the reverse situation was only 12 persons from 594 (2.0%). (Eds note: this whole section makes little sense? What were the BMDs? The last sentence is completely meaningless.) CONCLUSIONS: The discordance rate between the femur neck and lumbar spine was as high as 33%, and was the highest in the osteopenia persons in their 60's. Therefore, in these persons the BMD of both sites should be checked together, but if not, the lumbar BMD should be checked first.
Absorptiometry, Photon ; Bone Diseases, Metabolic ; Classification ; Diagnosis ; Female ; Femur Neck ; Hip* ; Humans ; Osteoporosis ; Spine*

INTRODUCTIONTo review the definitions of the metabolic syndrome according to various expert groups and assess their relevance to clinical practice.

MATERIALS AND METHODSMedline searches were conducted to identify studies which addressed: (i) the utility of the metabolic syndrome compared to multivariable predictive functions for the identification of individuals at high risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), (ii) the importance and definition of obesity in the definition of the metabolic syndrome and (iii) the impact of lifestyle and pharmacological interventions designed to reduce the risk of cardiovascular disease in those with and without the metabolic syndrome.

RESULTSAlthough inferior to multivariable risk scores in predicting T2DM and CVD, the metabolic syndrome represents a simple clinical tool, particularly for the prediction of T2DM. Obesity is not a critical component of the metabolic syndrome for identifying those at increased risk of CVD but may be important for predicting T2DM. If anything, pharmacological therapy, especially lipid lowering is as, if not more, effective in those with the metabolic syndrome than in those without.

CONCLUSIONSAlthough the metabolic syndrome appears to have limited utility for the identification of individuals at increased risk of T2DM or CVD, the diagnosis of the metabolic syndrome presents an opportunity to rationalise health services to deliver coordinated care to those with metabolic syndrome.

Cardiovascular Diseases ; etiology ; Diabetes Mellitus, Type 2 ; etiology ; Humans ; Metabolic Syndrome ; complications ; diagnosis ; Obesity ; complications

PURPOSE: Neonatal screening for inherited metabolic disease is aimed at identifying affected infants early, thus permitting medical intervention to prevent or minimize the effect of the disease. However, organic aciduria, most of which causes severe disease and mental retardation, is not yet screened routinely because of the difficulty of tests, sample collection, and expenditure of time and financial resources. This study was designed to develop a screening method for the detection of multiple organic aciduria and neuroblastoma, using dried urine filter paper. METHODS: The standard markers used for screening of organic aciduria were placed on the filter paper and analysed with the modified organic acid analysis method. The extraction efficiency and stability of standard markers were tested for the purpose of adequacy as screening markers, and the method described herein was evaluated by analyzing filter paper samples obtained from both normal newborns and patients with known organic aciduria. RESULTS: The standard markers in the filter paper left in the room temperature over a period of 5 days were still stable without significant degradation. The level of specific organic acids obtained from known organic aciduria patients were easily detectable-enough to make the diagnosis. CONCLUSION: The filter papers soaked with urines obtained from newborns or patients with suspicious metabolic diseases are adequate for screening of organic acidurias and neuroblastoma. Sample delivery to the laboratory can be handled more easily with this method and even newborn screening could be applied in the future.
Diagnosis ; Health Expenditures ; Humans ; Infant ; Infant, Newborn* ; Intellectual Disability ; Mass Screening* ; Metabolic Diseases ; Neonatal Screening ; Neuroblastoma