Clinica Chimica Acta最新文献

{"title":"Exploring strategies to rapidly identify false positives in high-sensitivity cardiac troponin I assay: A prospective study","authors":"Anthony Desaegher ,&nbsp;Victor Marin ,&nbsp;Marie-Christine Beauvieux ,&nbsp;Brigitte Colombiès ,&nbsp;Margaux Lauga ,&nbsp;Sonia Alloug ,&nbsp;Selen Kalkan ,&nbsp;Gladys Castaing-Mouhica ,&nbsp;Geneviève Lacape ,&nbsp;Benoit Rucheton ,&nbsp;Julien Doublet ,&nbsp;Sandrine Dabernat ,&nbsp;Marie-Lise Bats","doi":"10.1016/j.cca.2024.119996","DOIUrl":"10.1016/j.cca.2024.119996","url":null,"abstract":"<div><h3>Background</h3><div>Cardiac troponin is the pivotal biomarker of myocardial injury, playing a central role in the diagnosis of acute coronary syndrome and various clinical situations. Nevertheless, challenges arise when patients exhibit elevated cardiac troponin levels in the absence of evident cardiac origin, as evidenced by extensive cardiac exploration, which suggests the presence of an interfering factor. Despite the high performance of high-sensitive cardiac troponin immunoassays, these tests remain susceptible to interferences that may lead to false-positives.</div></div><div><h3>Methods</h3><div>In the period between July 2021 and July 2024, 8129 patients were hospitalized in the cardiology departments of Bordeaux University Hospital with positive results for high-sensitivity cardiac troponin I. Among them, 15 patients were suspected of having false-positive results, based on clinical and biological observations.</div></div><div><h3>Results</h3><div>In this subpopulation, we evaluated prospectively various techniques, including serial dilutions, antibody-binding tubes, and alternative immunoassays (for cardiac troponin I and T) with the objective of identifying any potential analytical interference in their high-sensitive cardiac troponin I measurements. Our investigations revealed that 12 out of 15 suspected cases exhibited an interference on the high-sensitive cardiac troponin I assay.</div></div><div><h3>Conclusion</h3><div>In conclusion, we propose an original algorithm designed to identify high-sensitive cardiac troponin I false-positives. This algorithm can help clinicians to make prompt and informed decisions about patient care, and to avoid erroneous clinical interventions that may result from such interferences.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic instability in ovarian cancer: Through the lens of single nucleotide polymorphisms","authors":"Harshavardhani Canchi Sistla ,&nbsp;Srikanth Talluri ,&nbsp;Taruna Rajagopal ,&nbsp;Sivaramakrishnan Venkatabalasubramanian ,&nbsp;Nageswara Rao Dunna","doi":"10.1016/j.cca.2024.119992","DOIUrl":"10.1016/j.cca.2024.119992","url":null,"abstract":"<div><div>Ovarian cancer (OC) is the deadliest gynecological malignancy among all female reproductive cancers. It is characterized by high mortality rate and poor prognosis. Genomic instability caused by mutations, single nucleotide polymorphisms (SNPs), copy number variations (CNVs), microsatellite instability (MSI), and chromosomal instability (CIN) are associated with OC predisposition. SNPs, which are highly prevalent in the general population, show a greater relative risk contribution, particularly in sporadic cancers. Understanding OC etiology in terms of genetic basis can increase the use of molecular diagnostics and provide promising approaches for designing novel treatment modalities. This will help deliver personalized medicine to OC patients, which may soon be within reach. Given the pivotal impact of SNPs in cancers, the primary emphasis of this review is to shed light on their prevalence in key caretaker genes that closely monitor genomic integrity, viz., DNA damage response, repair, cell cycle checkpoints, telomerase maintenance, and apoptosis and their clinical implications in OC. We highlight the current challenges faced in different SNP-based studies. Various computational methods and bioinformatic tools employed to predict the functional impact of SNPs have also been comprehensively reviewed concerning OC research. Overall, this review identifies that variants in the DDR and HRR pathways are the most studied, implying their critical role in the disease. Conversely, variants in other pathways, such as NHEJ, MMR, cell cycle, apoptosis, telomere maintenance, and <em>PARP</em> genes, have been explored the least.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icteria interference for 34 clinical chemistry analytes on different analytical platforms: Method or analyzer dependent?","authors":"Alen Vrtaric ,&nbsp;Marijana Miler ,&nbsp;Nora Nikolac Gabaj ,&nbsp;Valentina Vidranski ,&nbsp;Marina Bocan ,&nbsp;Petra Filipi ,&nbsp;Andrea Snagic ,&nbsp;Marija Kocijancic","doi":"10.1016/j.cca.2024.119993","DOIUrl":"10.1016/j.cca.2024.119993","url":null,"abstract":"<div><h3>Objectives</h3><div>In this study, we aimed to investigate the effect of increasing bilirubin concentration on 34 commonly measured clinical chemistry analytes on four different analytical platforms. We hypothesized that differences in icteria interference are not only method dependent, but also analyzer dependent.</div></div><div><h3>Methods</h3><div>Serum pool was prepared using leftover samples after routine laboratory blood testing. Serum pool was then spiked with dissolved bilirubin stock. Measurements were performed on all four locations at the same time. All measurements were done in duplicate. Mean value was calculated as: (value₁ + value₂)/2. Those values were multiplied by corresponding dilution factors obtained during the preparation of icteric samples. For each icteric sample (I_x), bias against native (I₀) sample was calculated as ((value I_x– valueI₀)/ valueI₀) × 100 %. Bias was calculated with actual average values. Obtained bias values were compared against acceptance criteria according to External quality assurance (EQA) providers. Difference in bilirubin concentration across platforms was tested using Friedman ANOVA. P values &lt; 0.05 were considered statistically significant. Data are collected and analyzed in MS Excel 2016 (Microsoft, Redmond, Washington) and MedCalc® Statistical Software version 20.015 (MedCalc Software Ltd, Ostend, Belgium).</div></div><div><h3>Results</h3><div>Many of the tested parameters demonstrated low sensitivity to icterus interference. The highest sensitivity to icterus was observed for triglycerides, cholesterol, and urate.</div></div><div><h3>Conclusions</h3><div>Our results indicate that while some common icteric interferences were consistent across all tested platforms, others were specific to the analyzer used, even when employing the same analytical methods.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kallmann syndrome: Diagnostics and management","authors":"Rajiv Kumar Yadav ,&nbsp;Baiyu Qi ,&nbsp;Jianping Wen ,&nbsp;Xiaokun Gang ,&nbsp;Santasree Banerjee","doi":"10.1016/j.cca.2024.119994","DOIUrl":"10.1016/j.cca.2024.119994","url":null,"abstract":"<div><div>Kallmann syndrome is a genetic disorder characterized by delayed or absence of puberty and a reduced or absent sense of smell (anosmia). Kallmann syndrome is a form of hypogonadotropic hypogonadism due to lack of the production of sex hormones which is associated with development of secondary sexual characteristics. Kallmann Syndrome is a genetically heterogeneous disorder, characterized by the combination of hypogonadotropic hypogonadism (a deficiency in sex hormone production) and anosmia. Germline mutations in <em>KAL1</em> gene causes deficiency in GnRH hormone followed by low level of circulating gonadotropin and testosterone which finally leads to the failure of puberty (development of secondary sexual characters). Kallmann Syndrome can be inherited in several manners including X-linked recessive (e.g., mutations within <em>KAL1</em>) and autosomal dominant and recessive forms. Germline mutation in <em>KAL1</em> gene was identified among 8% of patients with Kallmann Syndrome. A review of the recent literature done reveals numerous clinical manifestations in Kallmann Syndrome patients with the <em>KAL1</em> mutation, including microgenitalia, impotence, reduced libido, infertility, unilateral renal agenesis, and synkinesia. Genetic molecular diagnostics through prenatal diagnosis and preimplantation genetic testing are most significant way to reduce the risk of Kallmann syndrome in next generation. Complication associated with Kallmann syndrome can be prevented by early diagnosis, diet supplementation and medical therapy. Goal of therapeutic intervention is to the development of secondary sexual characteristics, build and sustain bone density as well as muscle mass and restore fertility. This review aims to explore the genetic diagnosis and management strategies for Kallmann Syndrome, particularly focusing on <em>KAL1</em> gene mutations.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical implications of opioid parent-metabolite ratios","authors":"Hsuan-Chieh Liao,&nbsp;William S. Phipps,&nbsp;Michael W. Keebaugh,&nbsp;Andrew N. Hoofnagle,&nbsp;Geoffrey S. Baird","doi":"10.1016/j.cca.2024.119995","DOIUrl":"10.1016/j.cca.2024.119995","url":null,"abstract":"<div><h3>Background</h3><div>The opioid epidemic has underscored the importance of urine drug testing in the management of chronic pain. However, interpreting test results can be challenging, especially in scenarios where medications may have been directly added to urine samples to simulate compliance.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of 9,690 opioid testing results using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The study aimed to define the expected ratios between parent drugs and metabolites for eight commonly prescribed opioids. Cases with a parent-metabolite ratio above the 95th percentile were subjected to chart review.</div></div><div><h3>Results</h3><div>A total of 13 cases appeared likely consistent with simulated compliance with buprenorphine, 2 with methadone, 14 with oxycodone, and one with hydrocodone. The unusual patterns of parent-metabolite ratio can also be associated with hyperacute drug exposures/use, pharmaceutical impurity, or underlying liver enzyme deficiency. Furthermore, patients who failed the decision limits could exhibit other illicit use or aberrant behaviors.</div></div><div><h3>Conclusion</h3><div>Laboratories conducting LC-MS/MS-based opioid testing can more objectively identify anomalies by analyzing parent-metabolite ratios. When in consultation with providers, laboratories can point to these data when suggesting the possibility of simulated compliance and help identify cases warranting further investigation.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of novel variants in hereditary spherocytosis patients by whole-exome sequencing","authors":"Li Qin ,&nbsp;Yujiao Jia ,&nbsp;Haoxu Wang ,&nbsp;Yuan Feng ,&nbsp;Junyan Zou ,&nbsp;Jianfeng Zhou ,&nbsp;Changshun Yu ,&nbsp;Bingqing Huang ,&nbsp;Ruixue Zhang ,&nbsp;Lihui Shi ,&nbsp;Jigang Xiao ,&nbsp;Yuping Zhao ,&nbsp;Qi Sun ,&nbsp;Zhijian Xiao ,&nbsp;Huijun Wang","doi":"10.1016/j.cca.2024.119989","DOIUrl":"10.1016/j.cca.2024.119989","url":null,"abstract":"<div><div>Defects in erythrocyte membrane proteins can cause the most common type of inherited hemolytic anemia, so called hereditary spherocytosis (HS). It is characterized by the appearance of spherocytes in peripheral blood, hemolytic anemia, splenomegaly, jaundice and gallstones. Due to difficulty of diagnosis solely based on aforementioned parameters, the addition of genetic testing seems to be effective and most acknowledged. Up to date, pathogenic variations in five genes encoding membrane proteins (<em>ANK1</em>, <em>SPTA1</em>, <em>SPTB</em>, <em>SLC4A1</em>, <em>EPB42</em>) are identified to cause HS. Here, we have studied the genetic spectrum in forty-one patients with clinically suspected HS and their families, as well as their genotype-phenotype correlations. Pathogenic mutations in <em>ANK1</em>, <em>SPTB</em>, <em>SLC4A1</em> and <em>SPTA1</em> were found in 17 (41.5 %), 12 (29.3 %), 7 (17.1 %) and 5 (12.2 %) patients, respectively. Deleterious variants include 12 missense, 15 nonsense, 12 frameshift, and 4 splicing variants. Among these variations 32 were novel. In our genotype-phenotype analysis, platelet levels in <em>SPTB</em> (p = 0.021) and <em>SLC4A1</em> (p = 0.02) patients were found to be significantly lower than <em>ANK1</em> patients. In addition, LDH levels in <em>SPTB</em> patients were remarkably lower than patients with <em>ANK1</em> mutations (p = 0.025).</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New practice of BCR::ABL1 standardization system based on p210 and p190 BCR::ABL1 reference materials","authors":"Yu Ma ,&nbsp;Yanxi Han ,&nbsp;Zhenli Diao ,&nbsp;Yuqing Chen ,&nbsp;Tao Huang ,&nbsp;Lei Feng ,&nbsp;Jian Jiang ,&nbsp;Yuanfeng Zhang ,&nbsp;Jinming Li ,&nbsp;Rui Zhang","doi":"10.1016/j.cca.2024.119991","DOIUrl":"10.1016/j.cca.2024.119991","url":null,"abstract":"<div><div>Quantification of <em>BCR::ABL1</em> monitors minimal residual disease, thus critical for patient stratification. While significant progress has been made in enhancing the accuracy of <em>p210 BCR::ABL1</em> quantification, no equivalent standardization has been conducted for <em>p190 BCR::ABL1</em>. Therefore, we developed <em>p190 BCR::ABL1</em> reference materials to calibrate the quantitative process through an innovative plasmid-based calibration strategy. Then, we further explored the use of <em>p190</em> and <em>p210</em> reference materials to standardize tests in 159 laboratories across China and assessed their detection capability utilizing quality assessment samples. Results suggested that after calibration, the coefficient of variation of detection results decreased from 50.8 %–57.4 % to 24.9 %–36.4 % for <em>p190</em>, and from 37.6 %–49.0 % to 19.1 %–28.5 % for <em>p210</em>. The percentage of laboratories within ± 2-fold of the target values increased from 77.1 %, 76.4 %, 73.2 %, and 74.5 % to 94.3 %, 95.5 %, 92.4 %, and 91.1 % for <em>p190</em> samples 2023S21–2023S24, and from 72.3 %, 86.2 %, 79.2 %, and 81.1 % to 98.1 %, 99.4 %, 98.1 %, and 96.2 % for <em>p210</em> samples 2023S11–2023S14. Overall, our study successfully developed and employed <em>p190</em> and <em>p210</em> reference materials to promote accuracy and comparability of <em>BCR::ABL1</em> quantification among laboratories.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbohydrate antigens Lewis a and Lewis b act as tumor markers cooperating with CA19.9 in the management of PDAC patients","authors":"Rossella Indellicato ,&nbsp;Michele Dei Cas ,&nbsp;Aida Zulueta ,&nbsp;Anna Caretti ,&nbsp;Delfina Tosi ,&nbsp;Claudia Cigala ,&nbsp;Gaetano Bulfamante ,&nbsp;Enrico De Nicola ,&nbsp;Giovanna Scifo ,&nbsp;Enrico Opocher ,&nbsp;Daniela Pistillo ,&nbsp;Gennaro Nappo ,&nbsp;Alessandro Zerbi ,&nbsp;Marco Trinchera","doi":"10.1016/j.cca.2024.119990","DOIUrl":"10.1016/j.cca.2024.119990","url":null,"abstract":"<div><h3>Background</h3><div>CA19.9 is the unique marker recommended for the preoperative staging and the follow-up of patients suffering from pancreatic ductal adenocarcinoma (PDAC) but up to 30% of PDAC patients maintain normal CA19.9 values and cannot be monitored in this way. Lewis a (Lea Galβ1,3[Fucα1,4]GlcNAc) and b (Leb, Fucα1,2Galβ1,3[Fucα1,4]GlcNAc) are antigens which are structurally similar to sialyl-Lewis a (Siaα2,3Galβ1,3[Fucα1,4]GlcNAc), the epitope of CA19.9.</div></div><div><h3>Methods</h3><div>We set an ELISA procedure determining the levels of Lea, Leb, and CA19.9 in the blood of healthy individuals or PDAC patients. Moreover, such antigens were also detected in cancer resections by immunofluorescence microscopy, and the levels of glycosyltransferase transcripts involved in Lewis antigen biosynthesis were determined by RT-qPCR.</div></div><div><h3>Results</h3><div>In our cohort of 116 healthy individuals, the distribution of circulating Lea and Leb was similar to that of CA19.9, allowing us to set putative cutoff values for both antigens. In a cohort of 115 PDAC patients, the differential distribution with respect to the controls was statistically significant for both antigens (p &lt; 0.001). Out of 37 patients presenting normal CA19.9 values, 15 patients presented Lea or Leb above the cutoffs. By immunofluorescence, Lea, Leb and CA19.9 were all detected in cancer resections and expression levels were heterogeneous among patients in terms of intensity, localization and diffusion. The levels of relevant glycosyltransferase transcripts were found to be heterogeneous between cancers of different patients and no association was detectable with the levels of any circulating antigen.</div></div><div><h3>Conclusions</h3><div>The concurrent quantification of Lea and Leb together with CA19.9 improves the management of PDAC patients.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MUC16/CA125 in cancer: new advances","authors":"Xin-Yu Zhang ,&nbsp;Lian-Lian Hong ,&nbsp;Zhi-Qiang Ling","doi":"10.1016/j.cca.2024.119981","DOIUrl":"10.1016/j.cca.2024.119981","url":null,"abstract":"<div><div>MUC16/CA125 is a common diagnostic marker for many types of cancer. However, due to the widespread expression of MUC16 in cancer, its specificity and sensitivity as a target are poor, which severely limits its clinical application. In recent years, various studies have shown that the clinical application potential of MUC16/CA125 has been greatly improved. The update of detection technology improves the accuracy and range of detection, and improves the early diagnosis rate of cancer. Targeting MUC16/CA125 is an important strategy for tumor therapy. Targeting residual amino acids, n-glycoylation structures or other targets on the surface of MUC16 cells can greatly improve the accuracy of detection and therapy. The new drug delivery method broke through the original technical shackles, targeted MUC16 positive cells more specifically and improved the drug efficacy. In this paper, the technological advances in detecting and identifying MUC16 targets and the great progress in cancer screening and treatment based on MUC16 as a target are described in detail, revealing the great potential of MUC16 as a target in cancer screening and treatment, and illustrating the potential clinical application value of MUC16.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tandem mass spectrometry-based assay for heparan-N-sulphatase in paediatric CSF: A potential pharmacodynamic biomarker for mucopolysaccharidosis type IIIA therapy","authors":"Roberto Speziale ,&nbsp;Michaël Hocquemiller ,&nbsp;Xin Mei ,&nbsp;Danilo Fabbrini ,&nbsp;Savina Malancona ,&nbsp;Karen Aiach ,&nbsp;Ralph Laufer ,&nbsp;Laura Orsatti","doi":"10.1016/j.cca.2024.119987","DOIUrl":"10.1016/j.cca.2024.119987","url":null,"abstract":"<div><div>Mucopolysaccharidosis type IIIA is a lysosomal storage disorder caused by mutations in the gene coding for heparan-N-sulphatase, a crucial enzyme in the degradation of heparan sulfate. In mucopolysaccharidosis type IIIA, heparan sulfate accumulates in the lysosomes, predominantly affecting the central nervous system. It is the most common and most severe form of mucopolysaccharidosis type III, with onset typically before the age of ten years. There is an ongoing effort to develop therapies that aim at restoring enzyme function in the brain. This study introduces a novel tandem mass spectrometry method for assessing heparan-N-sulphatase activity in pediatric cerebrospinal fluid from healthy and disease individuals.</div><div>Analysis of cerebrospinal fluid samples revealed marked differences in enzyme activity, with mucopolysaccharidosis type IIIA individuals exhibiting significantly reduced levels. This new method could serve as a valuable tool for evaluating the efficacy of future therapeutic interventions targeting sulphatase activity restoration in the brain.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}