Molecular Genetics and Metabolism Reports最新文献

{"title":"A case report of riboflavin transporter deficiency: A novel heterozygous pathogenic variant in the SLC52A3 gene","authors":"Elizabeth S. Tranel ,&nbsp;Bridget McGowan ,&nbsp;Andy Drackley ,&nbsp;Leon G. Epstein ,&nbsp;Vamshi K. Rao ,&nbsp;Nancy L. Kuntz ,&nbsp;Abigail N. Schwaede","doi":"10.1016/j.ymgmr.2024.101051","DOIUrl":"10.1016/j.ymgmr.2024.101051","url":null,"abstract":"<div><p>Riboflavin transporter deficiency (RTD) is a neurodegenerative disorder that presents from infancy to adulthood with a progressive axonal neuropathy characterized by a variety of neurologic symptoms including hearing loss, weakness, bulbar palsy, and respiratory insufficiency. Pathogenic variants in <em>SLC52A2</em> and <em>SLC52A3</em> are implicated in the pathogenesis of RTD type 2 and 3, respectively. Early identification of this disorder is critical, as it is treatable with riboflavin supplementation. We describe a 16-year-old female with a phenotype consistent with RTD3 found to have a novel heterozygous <em>SLC52A3</em> variant. Though RTD is typically considered an autosomal recessive condition, her heterozygous variant was thought to be disease causing after further genetic analysis and given her improvement in response to riboflavin supplementation. This case highlights the importance of reinterpretation of genetic testing, particularly when there is a high clinical suspicion for disease.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000041/pdfft?md5=2384068ffd729c5cdc4f4eb2a4f9fff2&pid=1-s2.0-S2214426924000041-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139470204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maximal dietary responsiveness after tetrahydrobiopterin (BH4) in 19 phenylalanine hydroxylase deficiency patients: What super-responders can expect","authors":"Jariya Upadia ,&nbsp;Kea Crivelly ,&nbsp;Grace Noh ,&nbsp;Amy Cunningham ,&nbsp;Caroline Cerminaro ,&nbsp;Yuwen Li ,&nbsp;Meredith Mckoin ,&nbsp;Madeline Chenevert ,&nbsp;Hans C. Andersson","doi":"10.1016/j.ymgmr.2024.101050","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101050","url":null,"abstract":"<div><h3>Background</h3><p>Inherited phenylalanine hydroxylase deficiency, also known as phenylketonuria (PKU), causes poor growth and neurologic deficits in the untreated state. After ascertainment through newborn screen and dietary phenylalanine (Phe) restriction to achieve plasma Phe in the range of 120–360 μmol/L, these disease manifestations can be prevented. Poor compliance with protein restricted diets supported by medical food is typical in later years, beginning in the late toddler and teenage years. Pharmacologic doses of oral tetrahydrobiopterin (BH4; sapropterin dihydrochloride) is effective in reducing plasma Phe in about 40–50% of PKU patients but effectiveness is highly variable.</p></div><div><h3>Objective</h3><p>To assess the maximal responsiveness to 20 mg/kg/day oral BH4 as it affects plasma Phe and dietary Phe allowance in PKU patients.</p></div><div><h3>Materials and methods</h3><p>This was a single-center, retrospective observational study, combining case reports of individual patients. We reported an outcome of 85 patients with PKU who were trialed on BH4. Phe levels and dietary records of 19 BH4 “super-responders” were analyzed.</p></div><div><h3>Results</h3><p>Overall, 63.5% of the patients (54/85) were considered BH4 responders. However, we quantitated the dietary liberalization of 19 of our responsive patients (35%), those with at least a 2-fold increase in dietary Phe and maintenance of plasma Phe in treatment range. In these “super-responders”, the mean plasma Phe at baseline was 371 ± 237 μmol/L and decreased to 284 ± 273 μmol/L after 1 year on BH4. Mean dietary Phe tolerance increased significantly from 595 ± 256 to 2260 ± 1414 mg/day (<em>p</em> ≤0.0001), while maintaining mean plasma Phe levels within treatment range. Four patients no longer required dietary Phe restriction and could discontinue medical food. The majority of patients had at least one BH4-responsive genotype.</p></div><div><h3>Conclusion</h3><p>This cohort demonstrates the maximally achievable dietary liberalization which some PKU patients may expect with BH4 therapy. Health benefits are considered to accrue in patients with increased intact protein.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S221442692400003X/pdfft?md5=00b0406d237de25554bf4b5f698a687b&pid=1-s2.0-S221442692400003X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139433765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Twelve-year review of galactosemia newborn screening in Taiwan: Evolving methods and insights","authors":"Hui-An Chen ,&nbsp;Rai-Hseng Hsu ,&nbsp;Li-Chu Chen ,&nbsp;Ni-Chung Lee ,&nbsp;Pao-Chin Chiu ,&nbsp;Wuh-Liang Hwu ,&nbsp;Yin-Hsiu Chien","doi":"10.1016/j.ymgmr.2024.101048","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101048","url":null,"abstract":"<div><h3>Background</h3><p>Galactosemia was introduced into Taiwan's routine newborn screening (NBS) program in 1985. This study presents a 12-year experience, emphasizing disease diagnosis and screening performance.</p></div><div><h3>Method</h3><p>NBS for galactosemia utilized dried blood spot samples taken 48–72 h post-delivery, with total galactose (TGal) level as the primary marker. Newborns with critical TGal levels were referred immediately, while those with borderline TGal underwent a recall test. GALT activity measurement was applied simultaneously as the second-tier marker. Further confirmatory tests, such as whole exome sequencing (WES), were conducted upon referral.</p></div><div><h3>Results</h3><p>From January 1^st, 2011, to December 31^st, 2022, 51 cases were identified from 817,906 newborns. Of these, nine individuals had persistently elevated TGal. Diagnoses included one case of GALT deficiency, one of GALM deficiency, and seven of GALE deficiencies. Notably, the classic galactosemia patient (GALT deficiency) presented with extreme high TGal and was referred to the hospital for diet management immediately. All affected patients were instructed to adopt a galactose-restricted diet. By the median age of 2.5 years, all exhibited normal development and liver function.</p></div><div><h3>Conclusion</h3><p>The incidence of classical galactosemia and its variants is extremely low in Taiwan. Incorporating WES into NBS has improved our ability to detect various galactosemia forms, enriching our understanding of the genetic underpinnings. While these newly discovered forms often present with milder initial elevations in TGal, specific biochemical investigations and regular monitoring are essential to understanding the long-term implications and outcomes.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000016/pdfft?md5=692f393044ccb9cc483117cc0b02fb1e&pid=1-s2.0-S2214426924000016-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139406388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytochrome P450 genes expression in human prostate cancer","authors":"Oksana Maksymchuk ,&nbsp;Ganna Gerashchenko ,&nbsp;Inna Rosohatska ,&nbsp;Oleksiy Kononenko ,&nbsp;Andriy Tymoshenko ,&nbsp;Eduard Stakhovsky ,&nbsp;Volodymyr Kashuba","doi":"10.1016/j.ymgmr.2024.101049","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101049","url":null,"abstract":"<div><p>CYP-dependent metabolites play a critical role in regulating the cell cycle, as well as the proliferative, invasive, and migratory activity of cancer cells. We conducted a study to analyze the relative gene expression of various <em>CYPs</em> (<em>CYP7B1, CYP27A1, CYP39A1, CYP51, CYP1B1, CYP3A5, CYP4F8, CYP5A1, CYP4F2, CYP2J2, CYP2E1, CYP2R1, CYP27B1, CYP24A1</em>) in 41 pairs of prostate samples (tumor and conventional normal tissues) using qPCR. Our analysis determined significant individual variability in the expression levels of all studied <em>CYPs,</em> both in the tumor and in conventionally normal groups. However, when we performed a paired test between the tumor and normal groups, we found no significant difference in the expression of the studied genes. We did observe a tendency to increase the level of <em>CYP1B1</em> expression in the tumor group. We also did not find any significant difference between the levels of the studied <em>CYPs</em> in the tumor and conventional normal groups at different stages of prostate cancer and pathomorphological indicators. Correlation analysis revealed the presence of a positive relationship between the expressions of some cholesterol-metabolizing <em>CYP</em> genes, as well as between genes responsible for vitamin D biosynthesis and cholesterol biosynthesis. We observed significant correlative relationships between the expression of <em>CYPs</em> and some prostate cancer-related genes (<em>CDH2, MMP9, SCHLAP1, GCR, CYP17A1, ACTA2, CXCL14, FAP, CCL17, MSMB, IRF1, VDR</em>). Therefore, the expression of <em>CYPs</em> is not directly associated with prostate cancer but is largely determined by genetic, epigenetic factors, as well as endogenous substrates and xenobiotics. The significant correlative relationship between <em>CYPs</em> and genes associated with cancer may indicate common regulatory pathways that may have a synergistic effect on the tumor, ensuring the survival of cancer cells.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000028/pdfft?md5=d4e30e5d5630847d7184e0f16959d1ec&pid=1-s2.0-S2214426924000028-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139406387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New mutations identified in a case of Glycogenin-1 deficiency","authors":"R. Pruvost ,&nbsp;M. Csanyi ,&nbsp;G. Lefebvre ,&nbsp;V. Biancalana ,&nbsp;E. Malfatti ,&nbsp;F. Cassim ,&nbsp;C. Oldfors ,&nbsp;L. Defebvre ,&nbsp;A. Oldfors ,&nbsp;C. Tard","doi":"10.1016/j.ymgmr.2023.101046","DOIUrl":"10.1016/j.ymgmr.2023.101046","url":null,"abstract":"","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426923000927/pdfft?md5=3edf17a4498720144ea4cc755c74730a&pid=1-s2.0-S2214426923000927-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139092451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editors: Concerning “Hyperleucinosis during infections in maple syrup urine disease post-liver transplantation” by Guilder et al","authors":"Chika Takano ,&nbsp;Erika Ogawa ,&nbsp;Natsuko Arai-Ichinoi ,&nbsp;Mika Ishige","doi":"10.1016/j.ymgmr.2023.101047","DOIUrl":"10.1016/j.ymgmr.2023.101047","url":null,"abstract":"","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426923000939/pdfft?md5=0d1a87a5fe3da26fd09fbfbd7669931d&pid=1-s2.0-S2214426923000939-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139092454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of T1 mapping in cardiac MRI for the follow-up of Fabry disease in a pediatric population","authors":"Oscar Werner ,&nbsp;Lydia Ichay ,&nbsp;Nabila Djouadi ,&nbsp;Fernando Vetromile ,&nbsp;Marie Vincenti ,&nbsp;Sophie Guillaumont ,&nbsp;Dominique P. Germain ,&nbsp;Marc Fila","doi":"10.1016/j.ymgmr.2023.101044","DOIUrl":"10.1016/j.ymgmr.2023.101044","url":null,"abstract":"<div><h3>Background</h3><p>Fabry disease (FD) is a rare X-linked lysosomal disorder caused by pathogenic variants in the alpha-galactosidase-A gene (<em>GLA</em>). Life threatening complications in adulthood include chronic kidney failure, strokes and the cardiac involvement which is the leading cause of mortality. Usually, it presents with hypertrophic cardiomyopathy, together with arrhythmia and conduction abnormalities. An early indicator is decreased T1 value on cardiac magnetic resonance (CMR). Enzyme replacement therapy (ERT) is effective on some extra-cardiac symptoms but its effect on cardiac lesions depends on the level of initial myocardial lesions. CMR is routinely used to monitor cardiac involvement in FD due to its capacity for tissular characterization. However, there is a lack of data on the pediatric population to understand how to integrate CMR into early therapeutic decisions.</p></div><div><h3>Method</h3><p>Monocentric longitudinal study carried out at Montpellier University Hospital from 2016 to 2022. All pediatric patients with FD were evaluated over time with clinical, biological, and cardiac imaging (CMR, echocardiography).</p></div><div><h3>Results</h3><p>Out of the six patients included, (3 males), five were treated with ERT during the study. Low T1 values were observed in 4 patients. The normalization of T1 values was observed after 4 years of ERT in 3 patients.</p></div><div><h3>Conclusion</h3><p>Due to the lack of strong clinical and biological markers of FD in pediatric patients, initiation and follow-up of ERT efficacy remain challenging. CMR with T1-mapping, a noninvasive method, could play a role in the evaluation of early cardiac impairment in young patients at diagnosis and during follow-up with or without ERT.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426923000903/pdfft?md5=a17a1b07d87bf4f764ca9b0414b0ec96&pid=1-s2.0-S2214426923000903-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139063631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma arginine levels in arginase deficiency in the “real world”","authors":"Pranoot Tanpaiboon ,&nbsp;Yue Huang ,&nbsp;Judy Z. Louie ,&nbsp;Rajesh Sharma ,&nbsp;Stephen Cederbaum ,&nbsp;Denise Salazar","doi":"10.1016/j.ymgmr.2023.101042","DOIUrl":"10.1016/j.ymgmr.2023.101042","url":null,"abstract":"<div><h3>Background</h3><p>Deficiency of arginase-1, the final enzyme in the urea cycle, causes a distinct clinical syndrome and is characterized biochemically by a high level of plasma arginine. While conventional therapy for urea cycle disorders can lower these levels to some extent, it does not normalize them. Until now, research on plasma arginine levels in this disorder has primarily relied on data from specialized tertiary centers, which limits the ability to assess the natural history and treatment efficacy of arginase-1 deficiency due to the small number of patients in each center and technical variations in plasma arginine measurements among different laboratories.</p></div><div><h3>Method</h3><p>In this study, we reported plasma arginine levels from 51 patients with arginase-1 deficiency in the database of Quest Diagnostics. The samples were collected from different US regions.</p></div><div><h3>Results</h3><p>The mean plasma arginine level in these treated patients was 373 μmol/L and the median level was 368.4 μmol/L. Our data set from 30 arginase deficiency patients with plasma amino acid data from five or more collections revealed significant correlations between the levels of arginine and five other amino acids (citrulline, alanine, ornithine, glutamine, and asparagine).</p></div><div><h3>Conclusion</h3><p>Despite treatment, the arginine levels remained persistently elevated and did not change significantly with age, suggesting the current treatment regimen is inadequate to control arginine levels and underscoring the need to seek more effective treatments for this disorder.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426923000885/pdfft?md5=d4696fb8ec564894faf9ff4ccf8e5545&pid=1-s2.0-S2214426923000885-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139063568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accurate determination of Biotinidase activity in serum by HPLC and its utilization as second tier test for the confirmation of initial positive newborn screening results","authors":"Abdul Rafiq Khan ,&nbsp;Souad Al-Enazi ,&nbsp;Areej Al-Gahtani ,&nbsp;Saleh Al-Zahrani ,&nbsp;Syed Muhammad Saad ,&nbsp;Khalid Mohammed Khan ,&nbsp;Ali Alothaim","doi":"10.1016/j.ymgmr.2023.101045","DOIUrl":"10.1016/j.ymgmr.2023.101045","url":null,"abstract":"<div><p>Diagnosis of Biotinidase deficiency (BTD) is extremely important to avoid several neurodevelopmental problems in early childhood. Colorimetric and fluorometric methods lack specificity and selectivity due to several interferences resulting in a high number of false positive results. We developed an HPLC method for BTD activity in serum with fluorescent detection. In colorimetric assays, biotinidase attacks the amide linkage of the artificial substrate biotinidyl-4-aminobenzoic acid (B-PABA) and releases <em>p</em>-aminobenzoic acid (PABA), which is converted to a purple dye by diazotization reaction. The newly developed method injects the reaction mixture directly into the HPLC column and quantifies using a six-point calibration curve without coupling and diazotization reaction. The method is linear over the 5–1000 μmol/L range. The detection and quantitation limits were 2.5 μmol/L and 5.0 μmol/L, respectively. When compared with colorimetric assay, the correlation coefficient (R²) was 0.9963. The within-assay and between-assay precision was &lt;10.0% for four levels of quality control samples. No significant variation in BTD activity was detected due to hemolysis, icteric, and lipemic samples. The newly developed method eliminates the potential interference due to the presence of aromatic amines and significantly reduces the false positive results observed with the colorimetric method. It is simple, specific, sensitive, faster in sample preparation, and requires a small sample volume. The newly developed HPLC method was used in our laboratory as a secondary tier test for initial positive BTD samples from newborn screening programs. To our knowledge, no similar HPLC method has been reported to date.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426923000915/pdfft?md5=80c3de99b4d4adaa8661b14ab1a20f2d&pid=1-s2.0-S2214426923000915-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139062682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers of Glycosaminoglycans (GAG) accumulation in patients with mucopolysaccharidosis type VI—LeukoGAG, Corneal Opacification (COM) and Carotid Intima Media Thickening (CIMT)","authors":"Young Bae Sohn ,&nbsp;Raymond Wang ,&nbsp;Jane Ashworth ,&nbsp;Pierre Broqua ,&nbsp;Mireille Tallandier ,&nbsp;Jean-Louis Abitbol ,&nbsp;Erin Jozwiak ,&nbsp;Laura Pollard ,&nbsp;Timothy C. Wood ,&nbsp;Tariq Aslam ,&nbsp;Paul R. Harmatz","doi":"10.1016/j.ymgmr.2023.101041","DOIUrl":"10.1016/j.ymgmr.2023.101041","url":null,"abstract":"<div><p>Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive lysosomal storage disorder characterized by deficient activity of arylsulfatase B enzyme (ASB) resulting in cellular accumulation of dermatan sulfate (DS) and chondroitin sulfate (CS) that leads to cell injury. Urinary glycosaminoglycans (GAG) are often used as a biomarker in MPS diseases for diagnosis and to monitor treatment efficacy. This study evaluated leukocyte GAGs (leukoGAG) and skin GAGs as alternate biomarkers representing intracellular GAG changes in patients with MPS VI and treated with enzyme replacement therapy (ERT). In addition, we evaluated corneal opacification measurements (COM) and carotid intima media thickness (CIMT) as indicators of GAG accumulation and tissue injury. The study was performed in a serial two-step design in a single center. A quantitative method to measure leukoGAG levels in leukocytes was developed in Study 1 to compare the GAG levels between MPS VI patients and a control group and to assess correlations between leukoGAG and urineGAG. Study 2 validated the leukoGAG measurement, assessed the effect of ERT infusion on leukoGAG and ASB activity in leukocytes, identified correlations between leukoGAG and other biomarkers, and assessed differences in GAG accumulation between MPS VI patients and control subjects. In Study 1, leukoCS and leukoDS levels were significantly higher in the MPS VI group than the control group (leukoCS: 37.9 ± 10.2 and 2.9 ± 1.5 μg/μg protein, respectively, <em>p</em> = 0.005; leukoDS: 0.26 ± 0.2 and 0.0 ± 0.0 μg/μg protein, respectively, <em>p</em> = 0.028) with positive correlations between leukoCS and urine CS and leukoDS and urineDS. In Study 2, leukoCS (32.0 ± 11.8 vs 6.9 ± 3.1 μg/mg protein, <em>p</em> = 0.005) and leukoDS (0.4 ± 0.1 and 0.2 ± 0.1 μg/mg protein, <em>p</em> = 0.020) were significantly higher compared with control subjects. Thus, these results highlight the potential of leukoGAG as a new biomarker representing intracellular GAG accumulation in MPS VI patients and may be valuable for patient management.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426923000873/pdfft?md5=1e2b2e713710c6dbe17b9e20130ee7fd&pid=1-s2.0-S2214426923000873-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139062644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}