Molecular Genetics and Metabolism Reports最新文献

{"title":"Outcome of two siblings with late-onset Krabbe disease following allogeneic hematopoietic stem cell transplantation: And review of literature","authors":"Montaha Almudhry ,&nbsp;Chitra Prasad ,&nbsp;Keng Yow Tay ,&nbsp;C. Anthony Rupar ,&nbsp;Harold Atkins ,&nbsp;Asuri N. Prasad","doi":"10.1016/j.ymgmr.2025.101242","DOIUrl":"10.1016/j.ymgmr.2025.101242","url":null,"abstract":"<div><h3>Objectives</h3><div>To compare delayed-onset Krabbe disease (KD) and outcomes between two siblings in relation to allogeneic hematopoietic stem cell transplantation (HSCT).</div></div><div><h3>Methods</h3><div>We provide a descriptive report on two siblings with late-onset KD and their clinical course before and after HSCT.</div></div><div><h3>Results</h3><div>The index case presented with neurological symptoms that were presumptively diagnosed with multiple sclerosis (MS). Despite treatment with immunotherapy, the patient continued to decline progressively, prompting reassessment in the neurometabolic clinic 17 years after symptom onset. Symmetrical white matter changes in the pyramidal tract and optic radiation on MRI, absence of GALC enzyme activity in the blood, and identification of a pathogenic and likely pathogenic <em>GALC</em> variants confirmed the diagnosis of late-onset KD. After the proband's diagnosis, late-onset KD was also confirmed in his two siblings. In contrast to the index case, the younger sibling underwent HSCT with milder symptoms, stabilizing neurocognitive status, and imaging findings. Despite advanced disease, the proband's condition has stabilized following HSCT.</div></div><div><h3>Discussion</h3><div>Late-onset KD is clinically heterogeneous in presentation. Recognizing its progressive course, variable clinical features, positive family history (if present), and characteristic imaging can enable timely recognition. Earlier intervention with HSCT may modify the outcome.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"44 ","pages":"Article 101242"},"PeriodicalIF":1.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657236","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":"Iron metabolism and hematological abnormalities in adult patients affected with mucopolysaccharidoses","authors":"Gabija Kaciulyte ,&nbsp;Goknur Yorulmaz ,&nbsp;Reena Sharma ,&nbsp;Simon A. Jones ,&nbsp;Robert Wynn ,&nbsp;Heather Church ,&nbsp;Karen Tylee ,&nbsp;Muzaffer Bilgin ,&nbsp;Ana Jovanovic ,&nbsp;Peter Woolfson ,&nbsp;Karolina M. Stepien","doi":"10.1016/j.ymgmr.2025.101243","DOIUrl":"10.1016/j.ymgmr.2025.101243","url":null,"abstract":"<div><div>Mucopolysaccharidoses are a heterogeneous group of rare lysosomal storage disorders (LSDs) caused by genetic mutations resulting in the deficiency of lysosomal enzymes responsible for the degradation of glycosaminoglycans (GAGs). The potential association of hematological abnormalities and clinical manifestations in MPS disorder highlights the importance of exploring the role of regular iron studies and hematological tests in at risk MPS patients as undiagnosed anemia has been shown to worsen clinical outcomes. In this study, therefore, we aimed to describe the hematological abnormalities and iron studies in adult patients with MPS disorders in the context of their therapies. Ninety-seven patients with MPS types I, II, III, IV and VI were included in the study (46 % females). The overall prevalence of iron deficiency anemia is 38 % in adult MPS cohort and affects 63 % of MPS III and 50 % of MPS I patients. It is more common in females with MPS I and IVA than males, post cardiac valve surgery and in patients with gastrointestinal dysfunction. There was high variability in Hb, mean corpuscular volume, serum iron and transferrin saturation among all the MPS subgroups, with results being higher in the HSCT and ERT group as compared to treatment naïve patients. The urine GAGs/creatine ratio negatively correlated with several critical parameters, including iron saturation (−0.07), serum iron (−0.06), Hb (−0.16), and hematocrit (−0.08). It was more pronounced among MPS III patients. Pancytopenia in treatment naive MPS III is associated with 7 to 20 fold increase of urine GAGs excretion. It is important to take into consideration hematological and iron study abnormalities in the management of MPS patients, as special approaches may be required for both intestinal health and anemia treatment.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"44 ","pages":"Article 101243"},"PeriodicalIF":1.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633977","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":"TANGO2 deficiency disorder in a 61-year-old male with episodic weakness, rhabdomyolysis, myotonia, and a novel missense variant","authors":"Henry Skocy ,&nbsp;Amber McFerren ,&nbsp;Daniel Cairns ,&nbsp;H. Mark Kenney ,&nbsp;Eran Tallis ,&nbsp;Amit S. Dhamoon ,&nbsp;Ellie Garbade ,&nbsp;Samuel J. Mackenzie","doi":"10.1016/j.ymgmr.2025.101241","DOIUrl":"10.1016/j.ymgmr.2025.101241","url":null,"abstract":"<div><div>TANGO2 Deficiency Disorder (TDD) is an autosomal recessive condition, most commonly diagnosed in childhood. Clinical features may include episodic movement disorders, seizures, cognitive impairment, hypothyroidism, and metabolic crises marked by rhabdomyolysis and life-threatening cardiac symptoms. A small number of adults, thought to largely represent the milder end of the phenotypic spectrum, have received a diagnosis of TDD in their 30's or 40's, though no genotype-phenotype correlations have been established to date. In this case report, we present a 61-year-old man with mild intellectual disability and recurrent muscle weakness who was diagnosed with TDD during an inpatient hospitalization for diverticulitis, prostatitis, and muscle weakness, ultimately attributed to rhabdomyolysis. Genetic testing revealed a deletion of exons 3–9 in <em>TANGO2</em> along with a novel missense variant (c.187G &gt; T; p.Gly63Cys) on the other allele. The patient was started on vitamin B-complex with additional pantothenic acid (500 mg daily) and subsequently noted improvement in his speech and energy levels. To our knowledge, this case describes the oldest known individual living with TDD by two decades. Additionally, the patient's relatively mild symptom profile and previously unreported missense variant in <em>TANGO2</em> may represent the first known example of genotype-phenotype correlation in TDD.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"44 ","pages":"Article 101241"},"PeriodicalIF":1.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550056","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":"GNE myopathy with premature ovarian failure: Case report and review of the literature","authors":"Shangyi Yang,&nbsp;Jine Yang","doi":"10.1016/j.ymgmr.2025.101240","DOIUrl":"10.1016/j.ymgmr.2025.101240","url":null,"abstract":"<div><div>GNE myopathy (GNE-M) is an ultra-rare disease characterized by muscle weakness in the extremities. The main etiology is that a pathogenic variation in the <em>GNE</em> gene leads to a reduction in sialic acid synthesis. However, whether it is associated with premature ovarian failure (POF) isunknown. Here we report a case of GNE-M with premature ovarian failure (GNE-M-POF). The clinical data of a case of GNE-M-POF in our hospital were collected. The historical trajectory, molecular features, diagnosis and treatment were analyzed retrospectively, and the literature was reviewed. Over the course of 12 years, the patient presents with a slow and progressively worsening clinical manifestation. She was amenorrheic at the age of 35 and never conceived. Her calf muscles, and some of her thigh muscles were severely atrophied, leaving her unable to walk on her own. POF may be an extra-muscular manifestation of GNE-M, and further research is needed to verify the association.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"44 ","pages":"Article 101240"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518672","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":"Arginase deficiency in Mexico: Insights from the experience of a metabolic reference center","authors":"M. Vela-Amieva ,&nbsp;C. Fernández-Lainez ,&nbsp;S. Guillén-López ,&nbsp;L. López-Mejía ,&nbsp;M.A. Alcántara-Ortigoza ,&nbsp;A. González del Angel ,&nbsp;L. Fernández-Hernández ,&nbsp;M.E. Reyna-Fabián ,&nbsp;B. Estandía-Ortega ,&nbsp;I. Ibarra-González ,&nbsp;S.W. Ryu ,&nbsp;H. Lee ,&nbsp;on behalf of Rare Diseases Mexican Effort Group (RaDiMEG)","doi":"10.1016/j.ymgmr.2025.101238","DOIUrl":"10.1016/j.ymgmr.2025.101238","url":null,"abstract":"<div><div>Arginase deficiency (ARG1d) is an inborn error of metabolism caused by pathogenic variants in <em>ARG1</em> gene, which causes a defective hydrolysis of arginine (Arg) to urea and ornithine. The molecular landscape of ARG1d in Mexico is poorly known. In this study, we present for the first time the clinical and genotypic overview of the largest cohort of ARG1d in Mexico. A retrospective analysis of the medical records of 24 ARG1d patients from a historical cohort of individuals with inborn errors of intermediary metabolism (1994–2024) from the National Institute of Pediatrics in Mexico City, was performed. Clinical, demographical, biochemical, anthropometric and molecular data were investigated in two moments, at diagnosis and at the last follow-up evaluation. It was found that only 7/24 patients were diagnosed by newborn screening (NBS). Additionally, we highlight the presence of the Portuguese NM_000045.4(ARG1):c.61C&gt;T or p.(Arg21*) variant as the most frequent cause of ARG1d in Mexico, carried by 27.7 % of the patients. Our findings emphasize the debilitating and progressive nature of ARG1d, the prolonged diagnostic odyssey experienced by the patients (6.7 years), and the importance of training healthcare professionals to recognize the clinical features suggestive of the disease. We also underscore the critical need to advance early detection through expanded NBS in our country, as the early-diagnosed patients exhibited less severe outcomes and improved nutritional status compared to late-diagnosed ones. It was also noted that Mexican ARG1d patients have significant difficulties adhering to current nutritional treatment, and access to ammonium scavengers, thus other therapeutic options could be desirable.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"44 ","pages":"Article 101238"},"PeriodicalIF":1.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492151","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":"Diagnostic challenges in ornithine transcarbamylase deficiency lacking genetic confirmation: liver biopsy versus human induced pluripotent stem cell technology","authors":"Alexander Laemmle ,&nbsp;Niklas Naef","doi":"10.1016/j.ymgmr.2025.101239","DOIUrl":"10.1016/j.ymgmr.2025.101239","url":null,"abstract":"","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"44 ","pages":"Article 101239"},"PeriodicalIF":1.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492152","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":"Overview of genetic mutations causing adrenoleukodystrophy: A case-series study","authors":"Mohadeseh Fathi ,&nbsp;Sheyda Khalilian ,&nbsp;Arezou Sayad ,&nbsp;Parvaneh Karimzadeh ,&nbsp;Farzad Ahmadabadi ,&nbsp;Soudeh Ghafouri-Fard ,&nbsp;Mohammad Miryounesi","doi":"10.1016/j.ymgmr.2025.101237","DOIUrl":"10.1016/j.ymgmr.2025.101237","url":null,"abstract":"<div><div>X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder resulted from mutations in the <em>ABCD1</em> gene located at the Xq28 locus. This gene encodes a transporter protein responsible for importing very-long-chain fatty acids into peroxisomes. This research seeks to elucidate the clinical manifestations linked to various mutations in the <em>ABCD</em> gene among Iranian patients with X-ALD, considering the diverse severity of symptoms observed in this disease. Totally, six variants, including a novel variant (c.1781-47G &gt; A) were identified in the <em>ABCD1</em> gene in the patients. All but one variant were classified as pathogenic or likely pathogenic; the remaining variant, c.1781-47G &gt; A, was identified as a variant of uncertain significance. This study broadens the spectrum of <em>ABCD1</em> mutations among Iranian patients, providing applicable information for appropriate genetic counseling in the affected families.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"44 ","pages":"Article 101237"},"PeriodicalIF":1.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470215","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":"Hypothesis: Taurine therapy of nephropathic cystinosis may correct the deficiencies of cysteamine therapy","authors":"Jess G. Thoene","doi":"10.1016/j.ymgmr.2025.101236","DOIUrl":"10.1016/j.ymgmr.2025.101236","url":null,"abstract":"<div><div>Untreated nephropathic cystinosis is a lethal autosomal recessive disease. The current specific therapy, cysteamine, ameliorates the renal function loss, but does not alter the renal Fanconi syndrome, short stature, muscle weakness, male infertility, and other concerns. The primary biochemical/physiological defect in cystinosis is failure to supply cysteine to mTOR via cystinosin. This leads mTOR to react in starvation mode, which stops cell differentiation, leading to proximal tubule loss, and ultimately renal failure. It also increases apoptosis and autophagocytosis rates, which may contribute to impaired growth. Many of the defects which occur in cystinosis are corrected by taurine in other conditions as described. Cystinosis patients have been shown to be severely deficient in plasma taurine. Although use of taurine is not yet reported in cystinosis <em>in vitro</em> or <em>in vivo</em>, given the safety of taurine, its deficiency in cystinosis, and its potency in correcting similar defects in other conditions, it appears reasonable to engage in a clinical trial of taurine in nephropathic cystinosis.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101236"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253361","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":"Exploring the burdens of women living with Fabry disease in Japan: A patient survey of 62 respondents","authors":"Masahisa Kobayashi ,&nbsp;Ikuko Kaku ,&nbsp;Nanae Goto ,&nbsp;Mio Tsuchiya ,&nbsp;Norio Sakai","doi":"10.1016/j.ymgmr.2025.101231","DOIUrl":"10.1016/j.ymgmr.2025.101231","url":null,"abstract":"<div><div>The challenges encountered by women living with Fabry disease in Japan are not well understood. This study aimed to elucidate the experiences of women with Fabry disease and their support networks from both female and male perspectives. A 22-question survey was conducted among patients with Fabry disease and their caregivers (≥18 years) in Japan between August and October 2023. Sixty-two recipients completed the questionnaire (11.5 % response rate); 47 (75.8 %) were female and the mean age was 52.4 years. Overall, 51 respondents (82.3 %) identified as patients, 2 (3.2 %) as caregivers, 6 (9.7 %) as both a patient and caregiver, and 3 (4.8 %) as “other”. In total, 43 respondents (69.4 %) were women with Fabry disease. Among life events surveyed, Fabry disease had the greatest impact for women during family planning. The most commonly reported concerns for women were inheritance of Fabry disease and impact on children, the main reasons for which were prejudice, stigma, and sense of guilt associated with inheritance. In all, 28.1 % of respondents felt family and colleagues understood women's challenges with Fabry disease, while 37.9 % believed their primary care physicians and 48.3 % felt their specialist physicians understood these challenges; 26.3 % thought women received tailored care, and 75.9 % felt the condition affects mental health. Women with Fabry disease in Japan face substantial emotional burdens and lack support from their community and physicians. Healthcare professionals can play a pivotal role by offering genetic counseling and developing support programs to alleviate mental burdens and provide education about the disease and family planning implications.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101231"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178013","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":"Family hypercholesterolemia due to LDLR gene in Vietnamese children: characteristics of phenotype and genotype","authors":"Mai Thi Thanh Do ,&nbsp;Dung Chi Vu ,&nbsp;Mai Thi Chi Tran ,&nbsp;Thao Phuong Bui ,&nbsp;Ngoc Thi Bich Can ,&nbsp;Khanh Ngoc Nguyen","doi":"10.1016/j.ymgmr.2025.101235","DOIUrl":"10.1016/j.ymgmr.2025.101235","url":null,"abstract":"<div><h3>Background</h3><div>Familial hypercholesterolemia (FH) results in elevated LDL cholesterol, contributing to atherosclerosis and early-onset cardiovascular disease. Mutations in the low-density lipoprotein receptor gene are the most common cause of familial hypercholesterolemia. Information regarding hypercholesterolemia in low- and middle-income nations is inadequate. This research aimed to characterise the phenotype and genotype of Vietnamese children diagnosed with familial hypercholesterolemia.</div></div><div><h3>Methods</h3><div>This study included twenty-one children diagnosed with familial hypercholesterolemia from 15 unrelated families. Data regarding physical characteristics, biochemical testing, cardiac ultrasound, coronary angiography, and dual-source computed tomography were gathered at diagnosis and follow-up. Next-generation and Sanger sequencing were performed to identify disease-causing variants in twenty-one index cases.</div></div><div><h3>Results</h3><div>We found eighteen heterozygous and two homozygous/one compound heterozygous FH cases. Fourteen distinct variants were identified, with the most prevalent being c.664 T &gt; C and c.681C&gt;G, and exon 15 deletion. Furthermore, we identified the c.161A&gt;C variant, which remains unreported in the literature. The median age at diagnosis was 6.7 years (0.5–17.5) and 8.3 years (6.3–13.3) in heterozygous and homozygous/compound heterozygous groups, respectively. 100 % homozygous/compound heterozygous cases and 16.7 % heterozygous cases presented xanthomas. The median plasma levels of LDL in heterozygous and homozygous/compound heterozygous groups were 6.6 mmol/l (3.8–12) and 10.8 mmol/l (10.7–11.7), respectively.</div></div><div><h3>Conclusions</h3><div>FH can appear early in childhood, and xanthomas primarily manifest in homozygous FH patients. <em>LDLR</em> gene variants in Vietnamese FH children were diverse, with 14 variants in 21 cases.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101235"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144196303","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}