Molecular Genetics and Metabolism Reports最新文献

{"title":"A GALNT3 mutation causing Hyperphosphatemic familial Tumoral calcinosis","authors":"","doi":"10.1016/j.ymgmr.2024.101128","DOIUrl":"10.1016/j.ymgmr.2024.101128","url":null,"abstract":"<div><p><strong><em>Aim</em></strong>Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) is an autosomal recessive disorder. This study investigates the etiology of HFTC in offspring from consanguineous parents.</p></div><div><h3>Methods</h3><p>Clinical assessment, imaging, and direct sequencing were utilized to elucidate the condition. Previously reported cases were also reviewed.</p></div><div><h3>Result</h3><p>We identified a consanguineous Chinese family with HFTC caused by an interesting homozygous G to A substitution in GALNT3 (c.1626 + 1G &gt; A). The parents were carriers.</p></div><div><h3>Conclusion</h3><p>This study represents the first report of HFTC in a consanguineous Chinese family due to an interesting GALNT3 mutation. We reviewed known GALNT3 variants and associated clinical features of calcification disorders. The phenotypic difference between homozygous and complex heterozygous mutations is not clinically significant. Gene mutations affect the function of proteins mainly by affecting their binding to polyvalent ligands.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000818/pdfft?md5=4392db20c521b201ccb09db1efb083e5&pid=1-s2.0-S2214426924000818-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141872252","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":"Clinical presentation and molecular genetics of Iranian patients with Niemann-pick type C disease and report of 6 NPC1 gene novel variants: A case series","authors":"","doi":"10.1016/j.ymgmr.2024.101124","DOIUrl":"10.1016/j.ymgmr.2024.101124","url":null,"abstract":"<div><p>Niemann Pick Type C disease is a rare and progressive neurodegenerative lysosomal storage disorder caused by autosomal recessive mutations in the NPC1 and NPC2 genes. It is characterized by the accumulation of multiple lipid species in the endolysosomal compartment, leading to neurodegeneration and involvement of the liver, spleen, and lungs. Niemann Pick Type C has a wide range of presentations and severities at different ages with different progression rates. According to the Human Gene Mutation Database, to date, 486 disease-causing mutations in the highly polymorphic NPC1 gene and &gt;20 mutations in the NPC2 have been reported. In the present study, we described the clinical, biochemical, and molecular profiles of 18 Iranian patients with Niemann-Pick Type C disease. Also, we describe six novel variants of the NPC1 gene, to our knowledge, not reported to date<strong>.</strong></p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000776/pdfft?md5=9c238334068df416a7f398e9f895688e&pid=1-s2.0-S2214426924000776-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141872253","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":"Clinical features and GCDH gene variants in three Chinese families with glutaric aciduria type 1: A case series and literature review","authors":"","doi":"10.1016/j.ymgmr.2024.101123","DOIUrl":"10.1016/j.ymgmr.2024.101123","url":null,"abstract":"<div><h3>Aim</h3><p>To analyze the clinical phenotype and genetic etiology of three cases of glutaric aciduria type 1 (GA1) in Chinese children.</p></div><div><h3>Methods</h3><p>We performed genetic and metabolic testing using tandem mass spectrometry (MS/MS) and gas chromatography–mass spectrometry (GC/MS), followed by trio whole-exome sequencing (trio-WES) and Sanger sequencing. A literature review on glutaric aciduria type 1 (GA1) in Chinese patients was also conducted.</p></div><div><h3>Results</h3><p>Sequencing results showed each case had compound heterozygous variants in <em>GCDH</em>(NM_000159.4): c.214C &gt; G (p.Arg72Gly) and c.411C &gt; G (p.Tyr137Term) (Case 1), c.214C &gt; G (p.Arg72Gly) and c.1204C &gt; T (p.Arg402Trp) (Case 2), and c.1228G &gt; T (p.Val410Leu) and c.395G &gt; A (p.Arg132Gln) (Case 3). These variants were inherited from their respective parents. Notably, the c.214C &gt; G variant found in two children was a novel variant not previously reported. A review of the literature revealed that, clinically, the majority of patients experienced onset in infancy and early childhood (82%). Additionally, 38.36% were diagnosed through newborn screening, with the primary reasons for the initial visit being delayed development (32.43%) and infections (21.61%). The most common clinical manifestations included increased head circumference (77.19%) and motor developmental delay (65.15%). Biochemically, patients exhibited significant elevations in C5DC (98.51%) and C5DC/C8 (94.87%) in blood, as well as GA (94.37%) and 3OHGA (69.39%) in urine. Radiographically, patients showed a high prevalence of abnormalities in cranial MRI (86.15%) and EEG (73.33%). Genetically, 67 distinct <em>GCDH</em> gene variants were identified among 73 patients, with missense variants being the most prevalent type (73.97%). The most frequent variant was c.1244-2 A &gt; C, observed in 17.12% of cases. Additionally, the majority of variant sites were located in exons 11 (25.37%) and 6 (22.39%).</p></div><div><h3>Conclusion</h3><p><em>GCDH</em> variants were identified as the causative factors in the three children. The discovery of the novel variant (c.214C &gt; G) expands the spectrum of pathogenic <em>GCDH</em> variants. These findings facilitate the diagnosis and treatment of affected children and provide a basis for genetic counseling and prenatal diagnosis for their families.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000764/pdfft?md5=06a5dceb24df8be6f0d4d4a4be63f7c2&pid=1-s2.0-S2214426924000764-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141872254","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":"Avalglucosidase alfa in infantile-onset Pompe disease: A snapshot of real-world experience in Italy","authors":"","doi":"10.1016/j.ymgmr.2024.101126","DOIUrl":"10.1016/j.ymgmr.2024.101126","url":null,"abstract":"<div><h3>Introduction</h3><p>Infantile-onset Pompe disease (IOPD) is due to mutations in the <em>GAA</em> gene leading to profound deficiency of the lysosomal enzyme α-1,4-glucosidase. The disease is characterized by severe hypotonia, hypertrophic cardiomyopathy, macroglossia, and liver enlargement with onset in the first months of life. In the late-onset form (LOPD), muscle signs predominate with a clinical picture resembling muscle dystrophies. Enzyme replacement therapy with alglucosidase alfa (rhGAA) has been available since 2006 and patients treated with the enzyme show improved outcomes. Nevertheless, there is evidence that some patients have a suboptimal response or, after an initial improvement, reach a plateau with stabilization of the clinical picture. Thus, a new enzyme formulation, avalglucosidase alfa (neoGAA), with a higher degree of mannosylation, was developed.</p></div><div><h3>Methods</h3><p>We conducted a multicenter survey that collected data on four patients with IOPD, aged 6 to 16 years, who were switched to neoGAA thanks to a compassionate use program, after being treated for an average of 11.5 years with rhGAA. Follow-up data, including biochemical parameters and clinical features, were analyzed to determine clinical outcomes and the safety profile after a mean of 9 months.</p></div><div><h3>Results</h3><p>Patients with IOPD who were treated with neoGAA showed a positive change in biomarker levels. Moreover, the clinical picture revealed improved motor performance and cardiac parameters in patients who previously responded poorly.</p></div><div><h3>Conclusion</h3><p>This study highlights the improved efficacy of neoGAA, as a next generation enzyme replacement therapy, in 4 Italian patients with IOPD. Several clinical parameters showed a positive response to the new formulation suggesting that, if used at diagnosis, neoGAA may result in better outcomes for patients with IOPD.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S221442692400079X/pdfft?md5=a4b241ce8693ff7d5b4f6c6c636e3b13&pid=1-s2.0-S221442692400079X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141872282","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":"Expanding genetic and clinical aspects of Schwartz-Jampel syndrome: A report of two cases with literature review","authors":"","doi":"10.1016/j.ymgmr.2024.101125","DOIUrl":"10.1016/j.ymgmr.2024.101125","url":null,"abstract":"<div><p>Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive disorder characterized by muscle stiffness (myotonia) and chondrodysplasia. This disease is caused by biallelic loss of function mutations in the <em>HSPG2</em> gene, which encodes the core protein of perlecan. This study aims to investigate causative variants in two sisters born to consanguineous Iranian parents. Both patients were presented with myotonia and a mask-like face; moreover, they showed a less common symptom, gastrointestinal bleeding, which is not typical of SJS and has only been reported in one patient. Regarding the crucial role of perlecan in vascular structure and mucosal stability, bleeding disorders could be expected in perlecan dysfunctions. In addition to the case study, a comprehensive literature review was conducted to gather information on similar genetic variants, associated clinical features, and possible disease mechanisms. Results of this study contribute to our understanding of the genetic and clinical aspects of Schwartz-Jampel syndrome, and more importantly, the manifestation of gastrointestinal bleeding in patients with Schwartz-Jampel syndrome.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000788/pdfft?md5=fa2f12fb79b63365bfee2c20934a8efa&pid=1-s2.0-S2214426924000788-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141772127","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":"Desensitization of olipudase alfa-induced anaphylaxis in a child with chronic neurovisceral acid sphingomyelinase deficiency","authors":"","doi":"10.1016/j.ymgmr.2024.101120","DOIUrl":"10.1016/j.ymgmr.2024.101120","url":null,"abstract":"<div><p>Olipudase alfa is indicated for the non-central nervous system manifestations of Acid sphingomyelinase deficiency (ASMD). Anaphylaxis is a very rare and life-threatening adverse reaction described for this drug. Here, we report the case of a 2-year-old boy affected by chronic neurovisceral ASMD who experienced signs of hypersensitivity reactions to olipudase alfa since the administered dose of 1 mg/kg during dose escalation and a proper anaphylactic reaction during the second administration of the target therapeutic dose of 3 mg/kg. The treatment was stopped for 15 weeks and then a 7-step desensitization protocol with the infused dose of 0.03 mg/kg was applied. Subsequent gradual dose escalation was resumed, successfully reaching the dose of 0.3 mg/kg. Moreover, biochemical, and radiological disease indexes, which were increased during treatment discontinuation, have gradually improved since the restart of treatment. However, at the second administration of the dose of 0.6 mg/kg, the patient experienced another adverse drug reaction with facial urticarial rash and bronchospasm, requiring the administration of adrenaline, methylprednisolone, and inhaled salbutamol. This case report highlights the need to customize the olipudase alfa desensitization protocol according to individual tolerance and raises the issue of achieving the established therapeutic target in the most sensitive children.</p></div><div><h3>Synopsis</h3><p>We report a case of anaphylaxis to olipudase alfa in a child affected by chronic neurovisceral Acid sphingomyelinase deficiency (ASMD) and describe a 7-step desensitization procedure. This procedure, with the total administered dose of 0.03 mg/kg, followed by gradual dose escalation, allowed to reach the dose of 0.3 mg/kg without adverse reactions; however, at the second administration of the dose of 0.6 mg/kg our patient presented another adverse reaction suggesting the need of a different desensitization strategy.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000739/pdfft?md5=82b10ffed1460849e1b384c042dff86e&pid=1-s2.0-S2214426924000739-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141639380","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":"A 12-month, longitudinal, intervention study examining a tablet protein substitute preparation in the management of tyrosinemia","authors":"","doi":"10.1016/j.ymgmr.2024.101119","DOIUrl":"10.1016/j.ymgmr.2024.101119","url":null,"abstract":"<div><p>Protein substitutes (PS) without tyrosine (Tyr) and phenylalanine (Phe), are an essential source of synthetic protein in the treatment of tyrosinemia (HT). In the UK, the only available protein substitutes for HT are Tyr/ Phe free amino acid liquid or powders or formulations based on glycomacropeptide (CGMP). A tablet Tyr/ Phe free amino acid supplement (AAT) has now been introduced. The aim of this two-part prospective, longitudinal intervention study was to assess the efficacy, acceptability, and tolerance of AAT in children aged &gt;8 years with HTI. Part 1: was a 28-day acceptability/ tolerance study, part 2, was a 12-month extension study examining efficacy of AAT. Anthropometry and blood Tyr/ Phe were assessed. All subjects were taking NTBC [2-(2-nitro-4-triflourothybenzoyl) cyclohexane-1, 3-dione] with a Tyr restricted diet. Eight subjects with HTI were recruited 4 boys, and 4 girls with a median age of 14.3y (range 10.4–17.3); 3 were Caucasian and 5 of Pakistani origin. The median (range) protein equivalent from PS was 60 g/d (50–60), natural protein 20 g/d (15–30), and NTBC 30 mg/d (25–80). No subjects were taking Phe supplements. Five (63%) subjects completed part 1, with 4 taking all their PS requirements as AAT. Subjects reported AAT were tasteless and had no odour. No adverse gastrointestinal symptoms were recorded, with two reporting improvements in abdominal discomfort. At 12 months, 4 subjects had a non-significant decrease in blood Tyr/ Phe compared to the 12 months pre-treatment. Median blood Tyr (μmol/ L) pre-intervention was 500 (320–590); and at 12 months, 450 (290–530). Median blood Phe (μmol/L) pre-intervention was 40 (30–40); and at 12 months 30 (30–50). Median height z scores remained unchanged, but there was a small decrease in weight z score (pre-study weight − 0.1 (−1.4 to1.1), 12 m − 0.3 (−1.4 to 1.3) and BMI (pre- study BMI 0.2 (−2 to 1.4), and 12 m, −0.1 (−2.5 to 1.5)).</p></div><div><h3>Conclusion</h3><p>AAT were useful for some adolescents with HTI who struggled with the taste and volume of conventional powdered and liquid PS.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000727/pdfft?md5=46d4d0250df9d68ed9a9dbf97a32f975&pid=1-s2.0-S2214426924000727-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629968","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":"Comparative study on incorporation of three recombinant human α-galactosidase A drugs (agalsidases) into cultured fibroblasts and organs/tissues of Fabry mice","authors":"Takahiro Tsukimura, Tomoko Shiga, Tadayasu Togawa, Hitoshi Sakuraba","doi":"10.1016/j.ymgmr.2024.101118","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101118","url":null,"abstract":"Enzyme replacement therapy (ERT) with recombinant human α-galactosidase A (α-Gal A) drugs (agalsidases) has been successfully used for treatment of Fabry disease, and three kinds of agalsidases are now available in Japan. To compare the biochemical characteristics of these drugs, especially focusing on their incorporation into cultured fibroblasts and organs/tissues of Fabry mice, we performed in vitro, cell, and animal experiments.","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141719555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole exome sequencing in energy deficiency inborn errors of metabolism: A systematic review","authors":"Fatimah Diana Amin Nordin ,&nbsp;Affandi Omar ,&nbsp;Balqis Kamarudin ,&nbsp;Timothy Simpson ,&nbsp;Julaina Abdul Jalil ,&nbsp;Yuh Fen Pung","doi":"10.1016/j.ymgmr.2024.101094","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101094","url":null,"abstract":"<div><p>Broad biochemical complexity and frequent overlapping clinical symptoms of inborn errors of metabolism (IEM), especially in energy-deficient patients, make accurate diagnosis difficult. In recent years, whole exome sequencing (WES), a comprehensive protein coding genetic test, has been used to diagnose patients at the molecular level. This study aims to evaluate the potential of WES in diagnosing energy-deficient IEM patients with limited biochemical findings and to identify common symptoms patterns in reported cases. Articles were identified using a combination of search terms in online databases (Science Direct, PubMed Central and Wiley). English-language case reports citing WES in the diagnosis of energy-deficient IEM patients were reviewed. This systematic review was conducted and reported using the ‘Preferred Reporting Items for Systematic Reviews and Meta-Analyses’ checklist. The quality and risk of bias were assessed using Joanna Briggs Institute critical appraisal tool. A total of 37 studies comprising of 54 case reports were included in this review. The median age of the patients was 0.4 years, with 55.6% being male and 44.4% being female. A total of 33 mutant genes were reported and they related to either metabolism or mitochondrial function. WES was able to identify mutations in 53 of 54 cases reported. The diagnosis of energy-deficient IEM patients is crucial, particularly given the challenging range of diverse clinical symptoms they present. The high accuracy of the WES technique appears to improve the diagnostic process. Further research defining more detailed guidelines is needed to engage with this rare set of genetic diseases.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000478/pdfft?md5=989f7f5d2ec46b5e6a98fa2cbf2e382f&pid=1-s2.0-S2214426924000478-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141606020","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":"Long-term safety of enzyme replacement therapy with agalsidase alfa in patients with Fabry disease: post-marketing extension surveillance in Japan","authors":"Makoto Arakawa,&nbsp;Yoshinori Ikeda,&nbsp;Hiromichi Otaka,&nbsp;Sanghun Iwashiro","doi":"10.1016/j.ymgmr.2024.101122","DOIUrl":"https://doi.org/10.1016/j.ymgmr.2024.101122","url":null,"abstract":"<div><p>Fabry disease is a rare inherited X-linked metabolic disorder in which deficient alpha-galactosidase A activity causes progressive build-up of globotriaosylceramide (Gb3) and multi-system dysfunction. Following approval of agalsidase alfa for Fabry disease in Japan in 2006, an 8-year all-case post-marketing surveillance (PMS) showed that the treatment was well tolerated and effective for managing disease progression in adult Japanese patients. The present nationwide prospective observational study extended the initial PMS by enrolling patients who continued agalsidase alfa treatment after the initial 8-year period in a 6.5-year extension survey. Patient information from the initial PMS and the extension survey was evaluated as a single data set (observation period: February 2007–September 2021). Of 493 patients in the initial PMS, 129 (45.0% male classic, 6.2% male non-classic, 48.8% female heterozygous phenotype) consented to participate in the extension survey and were included in the analysis. The mean duration of treatment was 9.6 years. A total of 145 adverse drug reactions (ADRs) occurred in 31 patients (24%), and 22 serious ADRs occurred in 12 patients (9.3%). Although serious cardiac, renal, or cerebrovascular adverse events decreased in frequency over time in male patients, serious cardiac events continued to occur in female patients, who showed higher incidence of cardiac complications at baseline. No new safety concerns were identified. Additionally, long-term agalsidase alfa treatment sustained the initial reduction in Gb3 concentrations without increasing the rate of anti-agalsidase antibody positivity. These findings suggest that agalsidase alfa treatment demonstrates continued safety and sustains patients' clinical course over the long term.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000752/pdfft?md5=742fd1fbaa21a30b8583fe73ed70c074&pid=1-s2.0-S2214426924000752-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141606021","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}