Molecular Genetics and Metabolism Reports最新文献

{"title":"Persistent elevations of alkaline phosphatase as an early indicator of GM1 gangliosidosis","authors":"Iskren Menkovic ,&nbsp;Monika Williams ,&nbsp;Neelam Makhijani ,&nbsp;Ruhan Wei ,&nbsp;Sarah P. Young ,&nbsp;Areeg El-Gharbawy ,&nbsp;Ashlee R. Stiles","doi":"10.1016/j.ymgmr.2025.101191","DOIUrl":"10.1016/j.ymgmr.2025.101191","url":null,"abstract":"<div><div><em>GLB1</em>-related disorders are autosomal recessive lysosomal diseases caused by enzymatic deficiency of β-galactosidase. Enzymatic deficiency of β-galactosidase may lead to one of two phenotypes, GM1 gangliosidosis or mucopolysaccharidosis IVB (MPS IVB). GM1 gangliosidosis is a neurodegenerative disorder with variable skeletal disease and involvement of other systems. The age of onset correlates with the extent of neurological involvement and established genotype/phenotype correlations. Mucopolysaccharidosis IVB is characterized by a skeletal dysplasia without neurological involvement. Diagnostic work-up for <em>GLB1-</em>related disorders includes enzyme analysis, biomarker analysis, molecular testing, and laboratory imaging studies.</div><div>We report a patient who presented with persistent elevations of alkaline phosphatase (ALP) and subtle dysmorphic facial features. An initial skeletal survey at birth was unrevealing; however, a repeat at 3 months of age was abnormal with anterior beaking of the lumbar vertebrae and hemivertebrae of the lower cervical spine. Urinary glycosaminoglycan (GAG) analysis revealed a marked elevation of keratan sulfate (KS). Clinical exome sequencing revealed pathogenic heterozygous variants in <em>GLB1</em>, consistent with <em>GLB1</em>-related GM1 gangliosidosis.</div><div>Our case demonstrates that persistent elevations of ALP may be an early indicator for GM1 gangliosidosis in an infant with progressive multisystem disease, indicating the need for early genetic consultation. This case also highlights the utility of repeat skeletal surveys with abnormalities detected at 3 months of age.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101191"},"PeriodicalIF":1.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080605","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":"Underdiagnosis of Fabry disease in minority ethnic groups","authors":"Claudia L. Church Smith ,&nbsp;Ashwin Roy ,&nbsp;Sarah Steeds ,&nbsp;Natalie Tuzcuoglu ,&nbsp;Christopher Wingrove ,&nbsp;Katherine Aitchison ,&nbsp;Claire Radford ,&nbsp;Laura A. Boyes ,&nbsp;Fiona Stewart ,&nbsp;Tarekegn Geberhiwot ,&nbsp;Richard P. Steeds","doi":"10.1016/j.ymgmr.2025.101194","DOIUrl":"10.1016/j.ymgmr.2025.101194","url":null,"abstract":"<div><div>Fabry disease (FD) is a rare, pan ethnic X-linked disorder. We explored ethnic representation in our service and a national patient organisation. An audit of the University Hospitals Birmingham FD cohort revealed that 9 % of index cases are minority ethnic, compared to 18.3 % of the population of England and Wales and 51.4 % of the Birmingham population. A similar split was observed in a national patient cohort, highlighting a need to identify the reasons for under-representation.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101194"},"PeriodicalIF":1.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080610","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":"Single centre retrospective review of plasma branched-chain amino acid levels in children with urea cycle disorders: Impact of treatment modalities and disease severity","authors":"Mildrid Yeo ,&nbsp;Preeya Rehsi ,&nbsp;Jie Ming Yeo ,&nbsp;Marjorie Dixon ,&nbsp;Anupam Chakrapani","doi":"10.1016/j.ymgmr.2025.101190","DOIUrl":"10.1016/j.ymgmr.2025.101190","url":null,"abstract":"<div><div>Branched-chain amino acids (BCAAs) are important for normal growth, development, and function. In urea cycle disorders (UCDs), plasma BCAA levels can be relatively low; this has been attributed variously to low protein intake, hyperammonaemia, and nitrogen scavenger treatment. We undertook a retrospective review of plasma BCAA levels in individuals with UCDs comprising ornithine carbamoyltransferase deficiency (OTCD <em>n</em> = 22), arginosuccinate lyase deficiency (ASLD <em>n</em> = 12), and argininosuccinate synthase deficiency (ASSD <em>n</em> = 6). Scavenger treatment groups comprised sodium benzoate (NaBz, <em>n</em> = 20), sodium phenylbutyrate (NaPBA, <em>n</em> = 5), NaBz+NaPBA (<em>n</em> = 14), and a control group receiving neither NaBz nor NaPBA (n = 14). In these treatment groups, respectively, median (IQR) plasma levels of leucine were 54 (32), 55 (25), 58 (19), and 91 (70) μmol/L (leucine was lower in the NaBz group than the control, <em>p</em> = 0.0282) and numbers of individuals (%) with leucine below normal were 10/20 (50 %), 1/4 (25 %), 10/14 (71 %), and 2/9 (20 %). The pattern was similar for isoleucine and valine. In the NaBz group, plasma BCAA levels were inversely correlated with protein intake (<em>p</em> ≤ 0.01 to <em>p</em> ≤ 0.001), plasma ammonia level (p ≤ 0.01 to <em>p</em> ≤ 0.0001), and scavenger dose (p ≤ 0.0001). We speculate that individuals with greater disease severity may be prone to BCAA deficiency, caused by BCAA consumption when alternative urea disposal pathways are used. Practical reflections on our audit were that to increase the proportion of plasma BCAA levels in the normal range, we needed to alter the biological value of protein intake, prescribe higher doses of scavenger to facilitate safe levels of protein intake, and give EAA supplements if indicated.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101190"},"PeriodicalIF":1.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080543","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":"Mucopolysaccharidoses types I and IIIA: Diagnosis and identification of novel polymorphisms associated with common mutations in Moroccan patients","authors":"Houda El Fissi ,&nbsp;Fadoua Bouzid ,&nbsp;Mohammed Said Sebbar ,&nbsp;Mohammed Amine Serghini ,&nbsp;Fouad Msanda ,&nbsp;Najat Alif","doi":"10.1016/j.ymgmr.2025.101186","DOIUrl":"10.1016/j.ymgmr.2025.101186","url":null,"abstract":"<div><h3>Background</h3><div>Mucopolysaccharidoses types I and IIIA are lysosomal storage diseases caused by mutations in the <em>IDUA</em> and <em>SGSH</em> genes, leading to deficiencies in α-L-iduronidase and heparan sulfamidase, respectively. These progressive, autosomal recessive disorders require early diagnosis.</div></div><div><h3>Purpose</h3><div>The study targeted and investigated the p.Pro533Arg mutation, known to cause mucopolysaccharidosis type I, and the p.Arg377Cys mutation, associated with mucopolysaccharidosis IIIA, in newly recruited Moroccan families. In parallel, variants/polymorphisms associated with these mutations were searched for.</div></div><div><h3>Methods</h3><div>Researchers employed RFLP assays for the p.Pro533Arg and p.Arg377Cys mutations and genomic PCR sequencing for variant detection. PolyPhen-2, MutPred2, SIFT, and MutationTaster were used to assess the pathogenicity of these variants, helping to evaluate their potential impact on disease.</div></div><div><h3>Results</h3><div>The p.Pro533Arg mutation was found in newly recruited families with Hurler syndrome, consistent with previous findings. Similarly, the p.Arg377Cys mutation was present in a newly recruited family with Sanfilippo A syndrome. DNA sequencing revealed five SNPs four in the <em>IDUA</em> gene and one in the <em>SGSH</em> gene with three <em>IDUA</em> SNPs and one <em>SGSH</em> SNP being novel.</div></div><div><h3>Conclusion</h3><div>The p.Pro533Arg and p.Arg377Cys mutations are common among Moroccan patients with MPS I and MPS IIIA, respectively. The ability to detect these mutations using restriction endonucleases allows for molecular diagnosis in affected families. Five polymorphisms were identified among them four are novel.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101186"},"PeriodicalIF":1.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080602","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 outcomes of enzyme replacement therapy from a large cohort of Korean patients with mucopolysaccharidosis IVA (Morquio A syndrome)","authors":"Juyoung Sung ,&nbsp;Insung Kim ,&nbsp;Minji Im ,&nbsp;Yoon Ji Ahn ,&nbsp;Sang-Mi Kim ,&nbsp;Ja-Hyun Jang ,&nbsp;Hyung-Doo Park ,&nbsp;Tae Yeon Jeon ,&nbsp;Kyung Rae Ko ,&nbsp;Se-Jun Park ,&nbsp;Jun Hwa Lee ,&nbsp;Eun Young Kim ,&nbsp;Chong Kun Cheon ,&nbsp;Eungu Kang ,&nbsp;Jung-eun Moon ,&nbsp;Young Bae Sohn ,&nbsp;Hsiang-Yu Lin ,&nbsp;Chih-Kuang Chuang ,&nbsp;Shuan-Pei Lin ,&nbsp;Sung Yoon Cho","doi":"10.1016/j.ymgmr.2025.101189","DOIUrl":"10.1016/j.ymgmr.2025.101189","url":null,"abstract":"<div><div>Mucopolysaccharidosis (MPS) IVA (Morquio A syndrome) is an autosomal recessive lysosomal storage disorder caused by a mutation affecting the enzyme <em>N</em>-acetylgalactosamine-6-sulfatase (EC 3.1.6.4, GALNS). Enzyme replacement therapy (ERT) has been shown to improve physical performance, quality of life, and respiratory function in patients with MPS IVA; however, owing to the rarity of MPS IVA, data on Korean patient characteristics are limited. This retrospective study reports clinical, radiographic, biochemical, and molecular findings, and analyzes long-term clinical outcomes, from the largest cohort of Korean patients with MPS IVA in a single center. The analysis included 17 patients from 14 families (58.8 % females; median [range] age at diagnosis 5.2 [1.8–33.7] years). The majority of patients (64.7 %) were classified as having a severe phenotype, 23 % had an intermediate phenotype, and 11.8 % had an attenuated phenotype. Skeletal manifestations and radiologic abnormalities at initial diagnosis included gait abnormality (35.3 %), short stature (23.5 %), chest deformity (23.5 %), scoliosis (17.6 %), kyphosis (11.8 %), dysmorphic face (6 %), hip pain (6 %), and leg deformity (6 %). Twelve different <em>GALNS</em> mutations were identified. Patients received ERT for a median (range) 7.4 years (3.0–12.1). Twelve patients reached final adult height, and all patients with the severe/intermediate phenotype had short stature (&lt;3rd percentile). Hemiepiphysiodesis was the most common surgical intervention among patients with the severe/intermediate phenotype. Drug-related adverse events (urticaria, rash, and anaphylaxis) were reported in four patients but were managed with antihistamines or desensitization. At follow-up, patients experienced improvements in functional independence measure score, ejection fraction, and the 6-min walk test compared with the pre-treatment baseline. This study provides real-world evidence for long-term stabilization of functional independence, endurance, and respiratory function among patients <strong>with MPS IVA</strong> treated with ERT, with no new safety concerns identified.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101189"},"PeriodicalIF":1.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080597","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":"Early diagnosis and follow-up of cerebrotendinous xanthomatosis in infant siblings presenting with congenital diarrhea: A case study from Saudi Arabia","authors":"Badr Mohammad Alsaleem ,&nbsp;Amna Basheer Ahmed ,&nbsp;Muhannad M. Alruwaithi ,&nbsp;Tarig Yassin Alamery ,&nbsp;Norah Nasser Alrajhi","doi":"10.1016/j.ymgmr.2025.101188","DOIUrl":"10.1016/j.ymgmr.2025.101188","url":null,"abstract":"<div><div>Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive neurometabolic genetic disease resulting from defects in the bile acid metabolism. This report describes cases diagnosed with CTX at an exceptionally early age – 4 months (Patient #2 and #3) – making them the youngest reported cases to date. All three presented with intractable congenital diarrhea, a hallmark manifestation of the disease. The diagnosis was confirmed through metabolic bile acids analysis in urine and genetic testing. The siblings were treated with Chenodeoxycholic acid (15 mg/kg/day) during the first year of treatment, resulting in an improvement in diarrhea in all three. However, cognitive function remained unimproved in one patient. Additionally, the presence of dysmorphic features, observed in these patients, have not been documented in previous CTX cases. The diagnosis prompted solely by the persistent diarrhea, highlights a critical, under-recognized early manifestation. These findings underscore the importance of raising awareness among physicians to enable early diagnosis and timely treatment, which may prevent disease progression.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101188"},"PeriodicalIF":1.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080593","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":"The metabolic landscape of tetrahydrobiopterin metabolism disorders in the Republic of Ireland","authors":"A. Fisher ,&nbsp;R. Boruah ,&nbsp;P.D. Mayne ,&nbsp;A.A. Monavari ,&nbsp;E. Crushell ,&nbsp;I. Knerr","doi":"10.1016/j.ymgmr.2024.101185","DOIUrl":"10.1016/j.ymgmr.2024.101185","url":null,"abstract":"<div><div>We present a case series of seven patients (5 males, 2 females, aged 7–38 yrs.) in Ireland with biopterin metabolism disorder. Five individuals had been diagnosed with dihydropteridine reductase (DHPR) deficiency and two with pyruvoyl tetrahydropterin synthase (PTPS) deficiency. While clinical symptoms were mainly neuro-developmental in nature, one of our patients with DHPR deficiency also had a mild pulmonary valve stenosis and patent arterial duct in infancy which subsequently resolved as a hitherto undescribed finding in this condition. Clinical outcomes in our patient cohort were overall satisfactory with the best outcomes in patients/siblings diagnosed on high-risk screening. In conclusion, early diagnosis, pathophysiology-driven treatments and frequent patient-specific treatment adjustments are crucial to sustain the best possible long-term outcomes.</div><div>Ireland's cohort of tetrahydropterin metabolism disorders highlights that improved outcomes are achieved with an early diagnosis which may not be attainable through newborn screening alone.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101185"},"PeriodicalIF":1.8,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024117","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":"Mitochondrial DNA variants in the pathogenesis and metabolic alterations of diabetes mellitus","authors":"Praveen Kumar K.S. ,&nbsp;M.N. Jyothi ,&nbsp;Akila Prashant","doi":"10.1016/j.ymgmr.2024.101183","DOIUrl":"10.1016/j.ymgmr.2024.101183","url":null,"abstract":"<div><div>Mitochondrial DNA (mtDNA) variants considerably affect diabetes mellitus by disturbing mitochondrial function, energy metabolism, oxidative stress response, and even insulin secretion. The m.3243 A &gt; G variants is associated with maternally inherited diabetes and deafness (MIDD), where early onset diabetes and hearing loss are prominent features. Other types of mtDNA variants involve genes ND4 and tRNA Ala genes that increase susceptibility to type 2 diabetes. Understanding these variants will provide a basis for developing targeted therapy to improve mitochondrial function and metabolic health. This article reviews the impact of mtDNA variants in diabetes, specifically with regards to the m.3243 A &gt; G variant effects on mitochondrial function and insulin secretion and other mtDNA variants that contribute to diabetes susceptibility, particularly ND4 and tRNA Ala gene variants. Data from extant literature were synthesised to obtain an understanding of how mtDNA variants affect diabetes pathogenesis. The main defect for MIDD is the m.3243 A &gt; G variant, which comprises enhanced susceptibility to metabolic syndrome and type 2 diabetes, followed by mitochondrial dysfunction, insulin resistance, and beta-cell dysfunction. Other mtDNA variants have also been reported to enhance diabetes susceptibility through mitochondrial dysfunction and insulin resistance. Increased production of reactive oxygen species (ROS) resulting from mitochondrial malfunction adds to metabolic and tissue damage. This happens in tissues crucial to glucose homeostasis, and it represents an important contribution of mitochondrial dysfunction to metabolic disturbances in diabetes. These mechanisms would underlie the rationale for developing targeted therapies to preserve mitochondrial function and, hence improve the metabolic health of diabetic patients.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101183"},"PeriodicalIF":1.8,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008385","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":"Genetic analyses of very long-chain acyl-coenzyme A dehydrogenase deficiency: A case report with a novel ACADVL variant","authors":"Wei Zhou,&nbsp;Huizhong Li,&nbsp;Li Yang","doi":"10.1016/j.ymgmr.2024.101184","DOIUrl":"10.1016/j.ymgmr.2024.101184","url":null,"abstract":"<div><h3>Background</h3><div>Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) is a rare autosomal recessive disease associated with variants in the <em>ACADVL</em> gene.</div></div><div><h3>Methods</h3><div>In December 2021, a neonate with VLCADD was identified via newborn screening in Xuzhou, China. Genetic testing and genetic family verification were performed via high-throughput sequencing combined with Sanger sequencing. The pathogenicity and functional impacts of novel variants were predicted using bioinformatics methods.</div></div><div><h3>Results</h3><div>Initial results obtained from tandem mass spectrometry blood screening were suggestive of VLCADD. Two compound heterozygous variants, c.753 T &gt; G (p.S251R) and c.1276G &gt; A (p.A426T), inherited from the father and mother, respectively, were detected in the <em>ACADVL</em> gene of this individual. The c.753 T &gt; G variant is novel and unreported.</div></div><div><h3>Conclusion</h3><div>These findings broaden the known mutational spectrum of the <em>ACADVL</em> gene in a Chinese population.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101184"},"PeriodicalIF":1.8,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008439","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":"Efficacy and safety of avalglucosidase alfa in Japanese patients with late-onset and infantile-onset Pompe diseases: A case series from clinical trials","authors":"Madoka Mori-Yoshimura ,&nbsp;Hirotaka Ohki ,&nbsp;Hideaki Mashimo ,&nbsp;Kenji Inoue ,&nbsp;Satoko Kumada ,&nbsp;Takashi Kiyono ,&nbsp;Akihiro Arimori ,&nbsp;Mitsunobu Ikeda ,&nbsp;Hirofumi Komaki","doi":"10.1016/j.ymgmr.2024.101163","DOIUrl":"10.1016/j.ymgmr.2024.101163","url":null,"abstract":"<div><h3>Background</h3><div>The efficacy and safety of avalglucosidase alfa for Pompe disease (PD) have been demonstrated in a global Phase 3 trial (COMET) in patients with late-onset PD (LOPD) and a global Phase 2 trial (Mini-COMET) in patients with infantile-onset PD (IOPD). This case series examines the individual results of three Japanese patients enrolled in these trials.</div></div><div><h3>Methods</h3><div>Case reports were assembled from data collected in the COMET and Mini-COMET trials. Detailed methods have been reported previously. The primary endpoint of COMET was change from baseline to week 49 in upright forced vital capacity percent (FVC %) predicted. The primary endpoint of Mini-COMET was safety and tolerability of avalglucosidase alfa. In both trials, key secondary endpoints included motor function tests and other qualitative measures of improvement. Changes in biomarkers and anti-drug antibodies were also assessed in both trials.</div></div><div><h3>Results</h3><div>Results for Japanese patients were representative of those from the overall populations in the COMET and Mini-COMET trials. We detail results for one Japanese patient with LOPD enrolled in the COMET trial and two Japanese patients with IOPD enrolled in the Mini-COMET trial. Importantly, avalglucosidase alfa was well tolerated at doses of both 20 mg/kg and 40 mg/kg in Japanese patients with LOPD and IOPD, respectively.</div></div><div><h3>Conclusions</h3><div>Although the number of patients was small, avalglucosidase alfa provides an efficacy and safety profile in Japanese patients representative of the overall populations from key global clinical trials.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101163"},"PeriodicalIF":1.8,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008091","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}