Molecular Genetics and Metabolism Reports最新文献

{"title":"Tissue-specific mitochondrial DNA, MT-TF, pathogenic variants in mitochondrial myopathies","authors":"Sylvia Rose ,&nbsp;Aurélien Trimouille ,&nbsp;Didier Lacombe ,&nbsp;Edoardo Malfatti ,&nbsp;Zahra Assouline ,&nbsp;Julie Steffann ,&nbsp;Isabelle Desguerre ,&nbsp;Arnold Munnich ,&nbsp;Agnès Rötig ,&nbsp;Giulia Barcia","doi":"10.1016/j.ymgmr.2025.101230","DOIUrl":"10.1016/j.ymgmr.2025.101230","url":null,"abstract":"<div><div>Mitochondrial myopathies are progressive muscle disorders caused by impaired mitochondrial oxidative phosphorylation, leading to reduced adenosine triphosphate production. Skeletal muscles have a high energy demand and are often the first to be affected. In addition to muscular symptoms (muscle weakness, effort intolerance, fatigue), the disease can affect the central and peripheral nervous systems, as well as the heart, liver, kidneys and endocrine system (diabetes). Molecular genetic diagnostic is currently based on leukocyte DNA obtained from blood samples, considered less invasive than muscle biopsy. We report four patients from three families with mitochondrial myopathy associated with ptosis, sensorineural hearing loss, epilepsy, tubulointerstitial nephropathy and cardiomyopathy. Genetic studies identified <em>MT-TF</em> variants (m.586G &gt; A, m.601G &gt; A, m.616 T &gt; C) with highly variable heteroplasmy levels in the same patient from one tissue to another (5 % to 70 % mutant load in circulating blood leukocytes and in muscle respectively).</div><div>We emphasize the importance of performing mtDNA analysis on muscle DNA, even in patients with negative blood leukocytes mtDNA sequencing, if there is strong clinical suspicion of mitochondrial myopathy.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101230"},"PeriodicalIF":1.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137879","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":"Adrenal insufficiency in inborn errors of metabolism and vice versa: Case reports and review of the literature","authors":"Ariane De Preter ,&nbsp;Anne Rochtus ,&nbsp;Peter Witters ,&nbsp;Daisy Rymen","doi":"10.1016/j.ymgmr.2025.101232","DOIUrl":"10.1016/j.ymgmr.2025.101232","url":null,"abstract":"<div><div>Primary adrenal insufficiency (PAI) in children is rare. It is mainly due to monogenetic disorders, with congenital adrenal hyperplasia being the most common cause in the first year of life. Although several inborn errors of metabolism (IEM) have been associated with PAI, increased awareness of PAI in IEM among both metabolic specialists and endocrinologists may improve patient outcomes. Here, we present a case series of patients with PAI and an IEM. Through a literature review, we discuss the various IEM that have been associated with adrenal insufficiency and explore the pathophysiological mechanisms linking these IEM to PAI. Based on the available data, pitfalls in the diagnosis of PAI in IEM are discussed and recommendations for early diagnosis are suggested. In addition, a non-exhaustive list of susceptible IEM was elaborated to encourage screening for PAI in IEM and vice versa.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101232"},"PeriodicalIF":1.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134558","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":"Cost analysis of newborn screening for spinal muscular atrophy using digital PCR vs. MLPA","authors":"Dolat Singh Shekhawat ,&nbsp;Amit Mittal ,&nbsp;Kuldeep Singh","doi":"10.1016/j.ymgmr.2025.101234","DOIUrl":"10.1016/j.ymgmr.2025.101234","url":null,"abstract":"","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101234"},"PeriodicalIF":1.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123973","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":"Real-world clinical outcomes in adult patients with Fabry disease: A 20-year retrospective observational cohort study from a single centre","authors":"Eamon P. McCarron ,&nbsp;Rajkumar Chinnadurai ,&nbsp;Jonathan Meyer ,&nbsp;Thomas Anderson ,&nbsp;Karolina M. Stepien ,&nbsp;Reena Sharma ,&nbsp;Peter Woolfson ,&nbsp;Ana Jovanovic","doi":"10.1016/j.ymgmr.2025.101229","DOIUrl":"10.1016/j.ymgmr.2025.101229","url":null,"abstract":"<div><h3>Introduction</h3><div>Fabry disease (FD) is an X-linked lysosomal storage disorder caused by alpha-galactosidase A deficiency, leading to the accumulation of globotriaosylceramide (Gb3) and progressive damage to the cardiovascular, renal, and cerebrovascular systems.</div></div><div><h3>Aims</h3><div>This study aimed to assess real-world clinical outcomes in FD patients, focusing on predominantly cardiovascular (CV), but also severe renal, and cerebrovascular outcomes, as well as CV and all-cause mortality. It also explored associations between age at diagnosis, Mainz Severity Score Index (MSSI), genetic mutations, and cardiometabolic risk factors such as smoking, hypertension, and obesity.</div></div><div><h3>Methods</h3><div>A retrospective observational cohort study of 405 patients with FD was conducted by reviewing medical records from a National Centre over a 20-year period. Clinical outcomes, predominantly cardiovascular, but also severe renal and cerebrovascular events and mortality were assessed. Age at diagnosis, MSSI, and cardiometabolic risk factors were also evaluated. Statistical comparisons were performed using the Mann-Whitney <em>U</em> test and Chi-square test, with significance set at <em>p</em> &lt; 0.05.</div></div><div><h3>Results</h3><div>Nearly half (48 %) of patients experienced a defined clinical outcome. Higher age at diagnosis and baseline MSSI was observed in patients with poorer outcomes. The c.644 A &gt; G (p.N215S) variant was linked with increased cardiovascular morbidity and mortality. Cardiometabolic risk factors such as smoking, hypertension, and obesity were common in patients with poorer outcomes. A high prevalence of arrhythmia, including paroxysmal atrial fibrillation (AF), was observed. Multi-morbidity was noted in deceased patients. Use of cardiometabolic therapies in at-risk groups (e.g. sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists) was low.</div></div><div><h3>Conclusion</h3><div>This study highlights the clinical burden of FD, particularly among males with the c.644 A &gt; G (p.N215S) variant. The frequent presence of cardiometabolic risk factors in patients with adverse outcomes reinforces the importance of early diagnosis, comprehensive risk evaluation, and individualised management to improve long-term prognosis.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101229"},"PeriodicalIF":1.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069567","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":"Clinical characteristics and interdepartmental collaboration for patients with Anderson–Fabry disease in Shiga Prefecture, Japan","authors":"Daisuke Tomioka ,&nbsp;Shunsuke Takagi ,&nbsp;Fumiko Nakazeki ,&nbsp;Ayano Takagi ,&nbsp;Ryosuke Fukazawa ,&nbsp;Ueno Yoshiki ,&nbsp;Yu Mimura ,&nbsp;Koichi Kato ,&nbsp;Hiroshi Sakai ,&nbsp;Kosuke Yamahara ,&nbsp;Shinji Kume ,&nbsp;Yoshihisa Nakagawa","doi":"10.1016/j.ymgmr.2025.101227","DOIUrl":"10.1016/j.ymgmr.2025.101227","url":null,"abstract":"<div><h3>Purpose</h3><div>Anderson–Fabry disease (AFD) is an X-linked lysosomal-storage disease caused by pathogenic variants in the gene encoding alpha-galactosidase A (<em>GLA</em>). The purpose of this study was to investigate the clinical characteristics of patients with AFD and the types of medical specialists necessary to manage them in a prefecture with a population of 1.48 million.</div></div><div><h3>Method</h3><div>We included patients with <em>GLA</em> variants among patients diagnosed by genetic testing with AFD and managed at Shiga University of Medical Science from April 2010 and May 2024. The clinical information and data of the specialists engaged for the management of the patients were obtained from their medical records.</div></div><div><h3>Result</h3><div>In this study, 14 individuals from five families (four males, 29 %) were diagnosed with AFD. The age at diagnosis ranged from 9 to 68 years (mean age 38 ± 20 years). The estimated prevalence in the prefecture was 0.99 per 100,000 people, 0.57 per 100,000 males, and 1.39 per 100,000 females. They received treatment by specialists from eight different departments, and the average number of departments in which they were managed was 3.3 overall, 4.2 for males, and 2.9 for females.</div></div><div><h3>Conclusion</h3><div>The family history and genetic testing are useful for the precise diagnosis and treatment of patients with AFD. As such patients require interdisciplinary treatment, interdepartmental cooperation should be promoted for their systemic care.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101227"},"PeriodicalIF":1.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929351","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":"X-linked hypohidrotic ectodermal dysplasia associated with gastroesophageal reflux disease","authors":"Yamato Hanawa ,&nbsp;Wataru Murasaki ,&nbsp;Tatsuya Ando ,&nbsp;Yuji Baba ,&nbsp;Hiroyuki Namba","doi":"10.1016/j.ymgmr.2025.101228","DOIUrl":"10.1016/j.ymgmr.2025.101228","url":null,"abstract":"<div><div>X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare genetic congenital disorder characterized by allelic heterogeneity, affecting the ectodermal structures. We present the case of a 4-month-old boy diagnosed with XLHED, suffering from recurrent aspiration pneumonia due to gastroesophageal reflux disease (GERD) since he was 1-month-old. This case highlights that GERD, when severe enough to cause aspiration pneumonia, may be associated with underlying ectodermal dysplasia, such as XLHED. In such cases, tube feeding may reduce the risk of pneumonia in infants with XLHED.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101228"},"PeriodicalIF":1.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923342","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":"Case report: Hepatocellular carcinoma in a patient with Pyridoxamine 5-phosphate oxidase (PNPO) deficiency undergoing pyridoxal 5-phosphate (PLP) treatment","authors":"Jesse Zhen Cheng Lee ,&nbsp;Chit Kwong Chow ,&nbsp;Cheuk-Wing Fung ,&nbsp;Stephen Tak Yau Lui ,&nbsp;Suet-Na Sheila Wong","doi":"10.1016/j.ymgmr.2025.101224","DOIUrl":"10.1016/j.ymgmr.2025.101224","url":null,"abstract":"<div><div>Pyridoxamine 5-phosphate oxidase (PNPO) deficiency is an autosomal recessive inborn error of metabolism that typically manifests as seizures resistant to conventional anticonvulsants, often presenting in the neonatal period to early infancy. One of the main treatments, pyridoxal 5-phosphate (PLP), carry a risk of liver toxicity. Concerns about liver toxicity have emerged not only with high doses of PLP but also with lower doses, prompting further investigation into the relationship between PLP treatment and liver complications in patients with PNPO deficiency. This report presents the first case report of hepatocellular carcinoma (HCC) in a patient with PNPO deficiency receiving PLP Pyridoxamine 5-phosphate oxidase (PNPO), identified before reaching teenager. This case underscores the importance of regular liver function monitoring for patients on long-term PLP therapy, suggesting a potential association between PLP treatment and the development of HCC, which has significant implications for clinical management strategies.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101224"},"PeriodicalIF":1.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929352","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":"Empagliflozin as treatment in glycogen storage disease type IB patients","authors":"María Arbelo Rodríguez ,&nbsp;Elena Márquez Mesa ,&nbsp;Cristina Lorenzo González ,&nbsp;Marina Gutiérrez Vilar ,&nbsp;Loredana Arhip ,&nbsp;Mónica Ruiz Pons ,&nbsp;José Pablo Suárez Llanos","doi":"10.1016/j.ymgmr.2025.101226","DOIUrl":"10.1016/j.ymgmr.2025.101226","url":null,"abstract":"<div><h3>Background</h3><div>Glycogen Storage Disease Ib (GSD Ib) is a disease that associates both neutropenia and neutrophil dysfunction, thereby causing recurrent infections and inflammatory bowel disease (IBD). As of now, the standard treatment of these complications has been the administration of granulocyte-stimulating factor (GCSF). However, recent studies have found that the use of empagliflozin, an antidiabetic drug, may have benefits by reducing the levels of 1,5 anhydroglucitol-6-phosphate (1,5-AG6P), a metabolite that accumulates in the cytosol of neutrophils and blocks the use of glucose.</div></div><div><h3>Results</h3><div>We therefore report our experience with three patients, one of them being a liver and kidney transplant recipient, with promising results. Morbidity has been greatly reduced in all cases consisting in weight gain, better neutrophil count and management of respiratory, osteoarticular and gastrointestinal comorbidities. Overall, an improvement in quality of life has been observed.</div></div><div><h3>Conclusion</h3><div>SGLT2 inhibitors, and specifically empagliflozin offer promising results in improving morbidity and quality of life in patients with GSD Ib. In the cases presented, including a patient with double liver-kidney transplant, a good profile of tolerance, safety and effectiveness has been observed.</div></div><div><h3>Synopsis</h3><div>Empagliflozin offers promising results in improving morbidity and quality of life in patients with GSD Ib, including the first double organ transplant patient treated with this drug.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101226"},"PeriodicalIF":1.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901911","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":"Lethal neonatal acidosis: Multiomic investigation of a novel HIBCH variant as the underlying cause","authors":"Sonali Patel ,&nbsp;Muhammad Zain-ul-abideen ,&nbsp;Genevieve Guyol ,&nbsp;Lance H. Rodan ,&nbsp;Casie A. Genetti ,&nbsp;Amy Z. Ren ,&nbsp;Philip Connors ,&nbsp;Patricia Davenport ,&nbsp;Ruby Bartolome ,&nbsp;Inderneel Sahai ,&nbsp;Vijay S. Ganesh ,&nbsp;Monica H. Wojcik","doi":"10.1016/j.ymgmr.2025.101223","DOIUrl":"10.1016/j.ymgmr.2025.101223","url":null,"abstract":"<div><div>HIBCH (3-Hydroxyisobutyryl-CoA hydrolase) deficiency is a rare, autosomal recessive inborn error of metabolism caused by pathogenic variants in <em>HIBCH</em> and typically presenting in the first year of life with hypotonia, seizures, global developmental delay, poor feeding, and ataxia. Biochemical abnormalities such as lactic acidosis and hyperammonemia may also be seen due to disruption of mitochondrial function, and the diagnosis may also be suspected by the presence of elevated hydroxy-C4-carnitine (C4-OH) detected from a blood sample with a definitive diagnosis obtainable by genetic analysis. We describe a neonate with mild hypotonia at birth who rapidly developed a severe metabolic acidosis, with her venous pH reaching a nadir of 6.374 within hours of life and death occurring within 15 h of life despite supportive measures. A genomic autopsy was undertaken using a blood sample saved prior to the neonatal death. Postmortem trio exome sequencing of the neonate and both parents revealed the neonate to be homozygous for a novel variant in <em>HIBCH</em> predicted to impact splicing, presumably resulting in severe deficiency of HIBCH enzyme activity. As both parents were carriers of the causal variant, anticipatory guidance was provided for risk reduction in future pregnancies. This case highlights the importance of comprehensive postmortem evaluation to evaluate severe, neonatal lethal conditions.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101223"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895923","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":"GM2 activator deficiency: An ultra-rare disorder with a new case and review of 22 published cases","authors":"Merve Yoldaş Çelik ,&nbsp;Burcu Köşeci ,&nbsp;Ezgi Burgaç ,&nbsp;Kanay Yararbaş","doi":"10.1016/j.ymgmr.2025.101225","DOIUrl":"10.1016/j.ymgmr.2025.101225","url":null,"abstract":"<div><div>GM2 activator deficiency (AB variant of GM2 gangliosidosis) is an ultra-rare autosomal recessive lysosomal storage disorder caused by pathogenic GM2A mutations. The loss of a functional GM2 activator protein disrupts GM2 ganglioside degradation, leading to progressive neurodegeneration. Although it shares clinical features with Tay-Sachs disease, GM2 activator deficiency remains a genetically and biochemically distinct disorder, with limited genotype-phenotype correlation due to the small number of reported cases.</div><div>This report presents a 33-month-old male with an infantile-onset phenotype, characterized by nystagmus, axial hypotonia, hyperacusis, and bilateral cherry-red spots. Genetic analysis identified a homozygous likely pathogenic c.262_264del (p.Lys88del) mutation, reinforcing its potential association with early disease onset. His clinical course was marked by progressive neurodegeneration, recurrent pulmonary infections, and severe feeding difficulties requiring gastrostomy placement.</div><div>In addition, previously published cases were reviewed to provide insights into the phenotypic spectrum, age of onset, and key clinical characteristics of GM2 activator deficiency. Among the 22 reported cases, 77.3 % exhibited an infantile-onset phenotype, while 18.2 % and 4.5 % had juvenile and adult-onset forms, respectively. Notably, cherry-red spots and hyperacusis were present in 94.1 % and 82.4 % of infantile cases but were strikingly absent in later-onset phenotypes.</div><div>This case report, supplemented by a literature review, offers a comprehensive overview of GM2 activator deficiency and underscores the importance of early molecular diagnosis in suspected cases</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101225"},"PeriodicalIF":1.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887940","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}