Molecular Genetics and Metabolism Reports最新文献

{"title":"Clinical characteristics of female Fabry disease patients with hypertrophic cardiomyopathy with mid-ventricular obstruction","authors":"Natsuko Inagaki ,&nbsp;Yasuyoshi Takei ,&nbsp;Tsuguhisa Hatano ,&nbsp;Yasuyuki Takada ,&nbsp;Yoshinao Yazaki ,&nbsp;Hisanori Kosuge ,&nbsp;Masatake Kobayashi ,&nbsp;Shinji Suzuki ,&nbsp;Tomohiro Umezu ,&nbsp;Masahiko Kuroda ,&nbsp;Kazuhiro Satomi ,&nbsp;Takeharu Hayashi","doi":"10.1016/j.ymgmr.2025.101196","DOIUrl":"10.1016/j.ymgmr.2025.101196","url":null,"abstract":"<div><div>Fabry disease (FD) is an X-linked lysosomal storage disease caused by mutations in <em>GLA</em>, which encodes α-galactosidase A (GLA). The loss or reduced activity of GLA leads to damage to multiple organs, resulting in the intracellular accumulation of globotriaosylceramide in various organs, including the heart, kidneys, and nervous system. Pathological changes in the heart typically result in concentric left ventricular hypertrophy. Hypertrophic cardiomyopathy (HCM) is an intractable disease characterized by unexplained left ventricular hypertrophy and diastolic dysfunction and is typically characterized by asymmetric left ventricular hypertrophy. We performed a causative gene analysis in patients with a rare subtype of HCM, HCM with mid-ventricular obstruction (HCM-MVO), and identified four patients with different pathogenic variants of <em>GLA</em>, which were clinically confirmed as FD. All four patients with FD and rare HCM-MVO morphology were female, and all cases involved the classical form of the disease. Three cases in whom lymphocyte Lyso-Gb3 was measured showed a marked decrease in Lyso-Gb3 after initiating enzyme replacement therapy (ERT). However, even after ERT, myocardial involvement worsened in the long term, and two patients experienced fatal arrhythmias. Therefore, it is difficult to determine the efficacy of myocardial involvement in FD using a lymphocyte-based Lyso-Gb3 assay system. In addition, none of these female patients had renal dysfunction, indicating a different pattern of organ damage compared with that previously reported in male patients.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101196"},"PeriodicalIF":1.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372440","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":"Carglumic acid as a treatment for persistent hyperammonemia in carnitine-acylcarnitine translocase deficiency: A case study","authors":"Hanım Babazade ,&nbsp;Tanyel Zubarioglu ,&nbsp;Esma Uygur ,&nbsp;Mehmet Şerif Cansever ,&nbsp;Ertuğrul Kiykim ,&nbsp;Çiğdem Aktuğlu Zeybek","doi":"10.1016/j.ymgmr.2025.101199","DOIUrl":"10.1016/j.ymgmr.2025.101199","url":null,"abstract":"<div><div>Carnitine-acylcarnitine translocase deficiency (CACTD) is a rare autosomal recessive fatty acid oxidation disorder resulting in energy deficiency due to impaired mitochondrial long-chain fatty acid transport. Hyperammonemia is a critical complication, often resistant to conventional treatment. Here, we report the case of a 7-month-old patient with CACTD, initially diagnosed at 10 days old, who presented with persistent hyperammonemia despite optimized medical nutrition therapy and conventional nitrogen scavenging with sodium benzoate. When hyperammonemia persisted, carglumic acid was introduced, leading to a sustained decrease in ammonia levels and effective long-term control. Carglumic acid, typically indicated for organic acidemias, proved beneficial in this CACTD case. The administration of carglumic acid not only provided acute resolution but also stabilized ammonia levels over prolonged follow-up. This case highlights carglumic acid as a potential therapeutic option for managing hyperammonemia in CACTD, underscoring the need for further studies to confirm its efficacy in long-term management of hyperammonemia in fatty acid oxidation disorders.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101199"},"PeriodicalIF":1.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349376","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 girl with intragenic variants in MARS2 and a chondrodysplasia phenotype","authors":"Hiroyuki Iijima ,&nbsp;Yuko Tsujioka ,&nbsp;Yoshiyuki Tsutsumi ,&nbsp;Gen Nishimura ,&nbsp;Yasushi Okazaki ,&nbsp;Kei Murayama ,&nbsp;Mitsuru Kubota ,&nbsp;Akira Ohtake","doi":"10.1016/j.ymgmr.2025.101198","DOIUrl":"10.1016/j.ymgmr.2025.101198","url":null,"abstract":"<div><h3>Background</h3><div>The human mitochondrial methionyl-tRNA is crucial for mitochondrial translation, serving as both initiator and elongator in polypeptide chains. The <em>MARS2</em> gene is responsible for binding methionine to mitochondrial tRNA. The clinical characteristics of <em>MARS2</em> intragenic variants are still largely unknown, since only a pair of siblings has been reported. The present patient presented with psychomotor developmental delay, growth failure, and spondylar dysplasia, which attracted attention in infancy and deteriorated with age.</div></div><div><h3>Case presentation</h3><div>A 7-month-old Japanese girl presented with failure to thrive, feeding difficulties, and psychomotor developmental delay. Radiological examination showed generalized skeletal alterations including mild spondylar dysplasia and abnormal ilia, which resembled mucopolysaccharidosis; however, the urinary glycosaminoglycan levels and alpha-L-iduronidase activity in the filter paper blood were normal. At age 33 months, she showed hyperlactatemia, and genetic analysis showed compound heterozygous novel variants (NM_138395.4: c.[277G &gt; A]; [409C &gt; T]: p.([Asp93Asn]; [Arg137Cys])) in the <em>MARS2</em> gene. After starting vitamin supplementation, her growth and development improved. Radiological examination at ages 2 and 4 years demonstrated a skeletal phenotype: platyspondyly with anterior beaking of the vertebral bodies; large proximal femoral epiphyses; and mild brachymesophalangy. The results of the mitochondrial respiratory chain activity examination using skin fibroblasts were within the normal range.</div></div><div><h3>Conclusion</h3><div>The skeletal phenotype may be a syndromic component of this disorder associated with <em>MARS2</em> intragenic variants.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101198"},"PeriodicalIF":1.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143354773","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":"Camptocormia as a feature of Mc Ardle's disease: A case report","authors":"Mathilde Nicolas ,&nbsp;Chloé Giret ,&nbsp;Sybille Pellieux ,&nbsp;Annick Toutain ,&nbsp;Anne-Marie Bergemer-Fouquet ,&nbsp;Pascal Laforêt ,&nbsp;Loic Bouilleau ,&nbsp;François Maillot","doi":"10.1016/j.ymgmr.2025.101197","DOIUrl":"10.1016/j.ymgmr.2025.101197","url":null,"abstract":"<div><div>Glycogen storage disease type 5 (GSD) is an autosomal recessive metabolic myopathy caused by pathogenic variants in the <em>PYGM</em> gene. We report the case of a patient with typical exercise intolerance with a “second wind” phenomenon, associated with camptocormia which is not commonly recognized as a feature of the disease. Molecular analysis of the <em>PYGM</em> gene the common c.148C &gt; T [p.(Arg50*)] variant and a missense variant in exon 12, c.1471C &gt; T [p.(Arg491Cys)]. GSD 5 and Pompe disease are both glycogen storage diseases in which axial involvement has been described. Although probably underestimated, severe axial myopathy has been rarely reported in GSD 5. We suggest that the long-lasting symptoms associated with camptocormia should be considered as possible initial features of GSD 5.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101197"},"PeriodicalIF":1.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143131346","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":"Impact of classical homocystinuria on health care resource utilization and costs in the United States: A retrospective cohort study","authors":"Mahim Jain ,&nbsp;Mehul Shah ,&nbsp;Kamlesh M. Thakker ,&nbsp;Andrew Rava ,&nbsp;Agness Pelts Block ,&nbsp;Colette Ndiba-Markey ,&nbsp;Lionel Pinto","doi":"10.1016/j.ymgmr.2025.101192","DOIUrl":"10.1016/j.ymgmr.2025.101192","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Classical homocystinuria (HCU) is a rare autosomal recessive disease that can affect multiple organ systems leading to increased health care resource utilization (HCRU) and costs. In this study, we aimed to utilize United States claims data to describe the all-cause HCRU and costs of HCU and to compare these when stratified by total homocysteine (tHcy) level.</div></div><div><h3>Methods</h3><div>This was a retrospective cohort study using Optum's de-identified Market Clarity Data from January 01, 2016, through September 30, 2021. Patients were initially selected if they had at least 1 International Classification of Diseases, Tenth Revision diagnosis code for homocystinuria (E72.11) or <em>homocystinuria</em> signs, disease, and symptoms term in the Market Clarity Dataset. Patients were subsequently selected by using a multi-parameter algorithm encompassing clinical and phenotypic characteristics and tHcy levels. Patients were excluded if they had cancer, a COVID-19 hospitalization, or pregnancy. Unadjusted all-cause HCRU and costs (adjusted to 2021 United States dollars) per patient per month (PPPM) over the follow-up period were reported by health care setting using descriptive statistics. Unadjusted linear regression was used for comparisons across tHcy levels.</div></div><div><h3>Results</h3><div>The overall study cohort included 143 eligible patients, 61 (42.7 %) had a tHcy level &lt; 50 μM and 82 (57.3 %) had a tHcy level ≥ 50 μM. Within the subgroup with tHcy level ≥ 50 μM, 54 (65.9 %) had a tHcy level 50 to &lt; 100 μM, and 28 (34.1 %) had a tHcy level ≥ 100 μM. In the overall cohort, 44.1 % of patients were female, mean age was 47.8 years, and most patients were White (76.9 %). Patients with higher tHcy levels had more unadjusted all-cause outpatient visits and pharmacy claims PPPM compared with those with lower tHcy levels. Mean total health care costs PPPM were $5139, $2722, and $925 in patients with tHcy ≥ 100 μM, 50 to &lt; 100 μM, and &lt; 50 μM, respectively (<em>p</em> &lt; 0.001). Among patients with tHcy ≥ 100 μM, mean costs of pharmacy claims ($1886), inpatient admissions ($1611), and outpatient visits ($1523) contributed the most to the total health care costs and total, inpatient, outpatient, and pharmacy costs were all significantly higher in patients with higher tHcy levels (all <em>p</em> ≤ 0.01).</div></div><div><h3>Conclusions</h3><div>All-cause HCRU and costs in patients with HCU were higher in patients with higher tHcy levels. A major portion of the costs were related to inpatient admissions, outpatient visits, and pharmacy claims. These results provide support for lowering tHcy levels through appropriate diet and treatment combination to reduce HCRU and the associated economic burden of HCU.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101192"},"PeriodicalIF":1.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143131402","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":"Analysis of readability of the top web searches for pediatric inborn errors of fatty acid metabolism","authors":"Katelyn Sawyer ,&nbsp;William Miller ,&nbsp;Courtney Popp ,&nbsp;Chloe Strege ,&nbsp;Cindy Eide ,&nbsp;Jakub Tolar","doi":"10.1016/j.ymgmr.2025.101195","DOIUrl":"10.1016/j.ymgmr.2025.101195","url":null,"abstract":"<div><h3>Background</h3><div>Disorders of fatty acid oxidation (FAOD) are estimated to account for around 1 in 10,000 live births, and with modern newborn screens, these conditions are often identified in childhood. However, not all parents will receive regular medical follow-up, and varying levels of parental health literacy can influence their reliance on online resources for information. Therefore, assessing the readability of online materials is critical to ensuring accessible and comprehensible patient education. Understanding the readability landscape informs our efforts to improve the quality of online resources and to support parents and patients in navigating the diagnosis of an FAOD.</div></div><div><h3>Objective</h3><div>Our goal was to evaluate the readability of public facing online materials concerning the 10 most common disorders of fatty acid oxidation, with consideration given to the recommended reading levels by the National Institutes of Health (NIH) and the American Medical Association (AMA).</div></div><div><h3>Methods</h3><div>Using Flesch-Kincaid, Coleman-Liau, and SMOG readability indices, we analyzed the top 25 internet search results for each disorder. Excluding empty or paywalled content, 232 publicly accessible materials were assessed.</div></div><div><h3>Results</h3><div>Mean readability ranged from 11.64 to 12.85, indicating generally higher complexity than recommended. Only 15.5 % of materials met NIH's 8th grade reading level guideline, and 3.9 % met AMA's 6th grade level. Variability existed between disorders, with percentages meeting guidelines ranging from 0 % to 25 % for NIH and 0 % to 8.3 % for AMA.</div></div><div><h3>Conclusion</h3><div>Ensuring readability of online resources for rare disorders of fatty acid oxidation is crucial, particularly given the prevalence of childhood diagnosis and varying levels of parental health literacy. Parents may rely on easily accessible but potentially complex materials found through online searches, highlighting the importance of aligning online content with recommended reading levels. Improving readability can enhance accessibility and understanding and facilitate informed decision-making and optimal care for patients.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101195"},"PeriodicalIF":1.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143131401","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":"FBN2 pathogenic mutation in congenital contractural arachnodactyly with severe skeletal manifestations","authors":"Yazhou Huang ,&nbsp;Xingxin Fang ,&nbsp;Linya Ma ,&nbsp;Jibo Zhang ,&nbsp;Chao Wang ,&nbsp;Taoran Gao ,&nbsp;Dan Peng","doi":"10.1016/j.ymgmr.2025.101193","DOIUrl":"10.1016/j.ymgmr.2025.101193","url":null,"abstract":"<div><h3>Background</h3><div>Congenital contractural arachnodactyly (CCA) is a rare autosomal dominant connective tissue disorder caused by mutations in the fibrillin-2 <em>(FBN2</em>) gene, characterized by crumpled ears, arachnodactyly, camptodactyly, dolichostenomelia, large-joint contractures and thoracolumbar scoliosis. Variations in the <em>FBN2</em> gene primarily include missense mutations and splice sites mutations. It is crucial to clarify whether missense mutations in the <em>FBN2</em> gene affect mRNA splicing.</div></div><div><h3>Methods</h3><div>We identified a novel pathogenic missense variant (c.3472G &gt; C, p.Asp1158His) in exon 26 of the <em>FBN2</em> gene using whole-exome sequencing (WES) and Sanger sequencing. In vitro, both the wild-type and mutant minigenes were successfully inserted into the pcMINI and pcMINI-C vectors to verify the impact of this variant on <em>FBN2</em> mRNA splicing. We utilized CLUSTALW to perform multiple sequence alignment to compare the evolutionary conservation of this variant and employed AlphaFold2 to predict the protein structure of the mutant.</div></div><div><h3>Results</h3><div>The likely pathogenic missense mutation (c.3472G &gt; C) results in the amino acid at position 1158 of the <em>FBN2</em> changing from aspartic acid (Asp) to histidine (His). Furthermore, DNA multiple sequence alignment indicates that this site is highly evolutionarily conserved. Functional assays and structure prediction indicated that the missense variant located at the edge of exon 26 of <em>FBN2</em> does not affect RNA splicing, instead, it changes the structure and function of the protein by altering the amino acid sequence.</div></div><div><h3>Conclusion</h3><div>This study enriches the pathogenic spectrum of CCA. Our research provides new insights for the diagnosis of CCA and may have an impact on genetic counseling.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101193"},"PeriodicalIF":1.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143131400","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":"Natural history of inflammation and impaired autophagy in children with Gaucher disease identified by newborn screening","authors":"V. Gragnaniello ,&nbsp;D. Gueraldi ,&nbsp;A. Saracini ,&nbsp;D. Velasquez Rivas ,&nbsp;C. Cazzorla ,&nbsp;L. Salviati ,&nbsp;A.B. Burlina","doi":"10.1016/j.ymgmr.2025.101187","DOIUrl":"10.1016/j.ymgmr.2025.101187","url":null,"abstract":"<div><h3>Introduction</h3><div>Gaucher disease is a lysosomal storage disease due to deficiency of glucocerebrosidase, leading to the accumulation of glucosylceramide, particularly in macrophages. In addition to storage, secondary abnormalities such as inflammation, cellular stress, and impaired autophagy may contribute to the disease pathogenesis. The onset and course of progression of these secondary abnormalities remains unclear. Owing to the increasingly widespread newborn screening programs, diagnosis can be made at a presymptomatic stage. Understanding the early natural course of the disease is important for optimal monitoring and management of such at-risk individuals.</div><div>The aim of our study is to investigate secondary abnormalities in very young children with type 1 Gaucher disease identified through neonatal screening.</div></div><div><h3>Materials and methods</h3><div>We enrolled five children (&lt;4 years old) with type I Gaucher disease in a presymptomatic stage and not receiving therapy. We assessed plasma cytokine profiles (TNFα, IL1β, and IL6 by ELISA), activation of pro-inflammatory p38 mitogen-activated protein kinase (MAPK) and the abundance of LC3-II as indicator of autophagic flux, by immunoblotting.</div></div><div><h3>Results</h3><div>All subjects exhibited elevated TNFα (mean 21.74 μmol/L, SD 37.48, range 2.37–88.72 μmol/L). The other cytokines analyzed were within normal range. Cellular stress (activation of p38) was present in the child with higher glucosylsphingosine (GluSph) accumulation. Additionally, all subjects showed a significant reduction in LC3-II (mean 88 %, SD 9 %, range 77–98 %), indicating reduced autophagic flux.</div></div><div><h3>Discussion</h3><div>We have identified the presence of inflammation with inhibition of autophagic flux in presymptomatic young children with a genetically confirmed high-risk of developing Gaucher disease. These findings contribute insights into the early course of Gaucher disease and support the management of at-risk individuals identified by newborn screening. Therapeutic interventions including specific enzyme replacement or other means to address inflammation or autophagy could delay or prevent the onset of symptomatic disease and consequential disability. Further clinical studies are warranted to explore these possibilities.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101187"},"PeriodicalIF":1.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122852","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":"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}