Molecular genetics and metabolism最新文献

{"title":"The clinical value of peripheral biogenic amine metabolites in early-treated phenylketonuria","authors":"Filippo Manti ,&nbsp;Emanuele Di Carlo ,&nbsp;Silvia Santagata ,&nbsp;Teresa Giovanniello ,&nbsp;Antonio Angeloni ,&nbsp;Francesco Pisani ,&nbsp;Tiziana Pascucci ,&nbsp;Francesca Nardecchia ,&nbsp;Claudia Carducci ,&nbsp;Vincenzo Leuzzi","doi":"10.1016/j.ymgme.2025.109088","DOIUrl":"10.1016/j.ymgme.2025.109088","url":null,"abstract":"<div><h3>Background</h3><div>Brain monoamine depletion is a well-established biochemical consequence of phenylketonuria (PKU). Similar alterations are expected in the peripheral biogenic amines (PBA), which share the same metabolic pathway with the brain. The present cross-sectional study explored the potential prognostic value of PBA by examining their relationship with blood Phe and clinical outcomes in early-treated adult PKU patients (ETPKU).</div></div><div><h3>Method</h3><div>53 ETPKU (age 27.14 ± 8.22 years; 35 female) and 60 age-matched control subjects (age 43 ± 13 years; 43 female) were enrolled in the study. A UPLC-ESI-MS/MS-based method was developed to assess 5-hydroxytryptophan (5-HTP), serotonin (5-HT), 5-hydroxyhyndolacetic acid (5-HIAA), and 3-<em>O</em>-methyldopa (3-OMD) in different blood-derived matrices. Life-long Index of Dietary Control (IDC), concurrent Phe, and Tyr were other parameters included in the analysis. Clinical outcome measures included IQ, executive functions (BRIEF), and psychiatric morbidity (CBCL/ASR and DSM-5-TR).</div></div><div><h3>Results</h3><div>5-HTP, 5-HIAA, and 3-OMD were significantly lower in PKU patients than in controls. 5-HIAA and 3-OMD were negatively correlated with concurrent Phe levels. Concerning outcome measures, IDC influenced IQ and BRIEF-Shift subscale, 5-HIAA BRIEF-Emotional Control, 3-OMD BRIEF-Initiate subscale, and Tyr BRIEF-Control subscale. In contrast, concurrent plasma Phe did not affect any outcome measures.</div></div><div><h3>Conclusion</h3><div>While confirming the negative influence of Phe on PBA in adult ETPKU, mimicking what happens in the brain, we also found an effect of PBA depletion on clinical outcome measures independent of Phe level. This suggests that PBA could serve as new candidate biomarkers for treatment monitoring in adult ETPKU patients.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 1","pages":"Article 109088"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “The effects of casein glycomacropeptide on general health status in children with PKU: A randomized crossover trial” [Molecular Genetics and Metabolism Volume 143, Issue 4, December 2024, 108607]","authors":"Alex Pinto ,&nbsp;Anne Daly ,&nbsp;Camille Newby ,&nbsp;Abigail Robotham ,&nbsp;Simon Heales ,&nbsp;Simon Eaton ,&nbsp;Helen Aitkenhead ,&nbsp;Kimberly Gilmour ,&nbsp;Richard Jackson ,&nbsp;Catherine Ashmore ,&nbsp;Sharon Evans ,&nbsp;Júlio Cesar Rocha ,&nbsp;Fatma Ilgaz ,&nbsp;Mary Hickson ,&nbsp;Anita MacDonald","doi":"10.1016/j.ymgme.2025.109077","DOIUrl":"10.1016/j.ymgme.2025.109077","url":null,"abstract":"","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 1","pages":"Article 109077"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Fabry disease screening and diagnostic efficiency: Integration of enzyme, biomarker, and next-generation sequencing testing","authors":"Yinghong Pan ,&nbsp;Lisa Sniderman King ,&nbsp;Elizabeth Vengoechea ,&nbsp;Ruby Liu ,&nbsp;Xiangwen Chen-Deutsch ,&nbsp;Sara Smith ,&nbsp;Yuanyuan Wang ,&nbsp;Cristina da Silva ,&nbsp;Polly Chakraborty ,&nbsp;Eshawnvie Kallu ,&nbsp;Babi Ramesh Reddy Nallamilli ,&nbsp;Taraka Donti ,&nbsp;Angela Walter ,&nbsp;Sean Kazemi ,&nbsp;Madhuri Hegde","doi":"10.1016/j.ymgme.2025.109082","DOIUrl":"10.1016/j.ymgme.2025.109082","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A (α-Gal A) due to pathogenic variants of the &lt;em&gt;GLA&lt;/em&gt; gene. This study reports findings from data collected through The Lantern Project, including results from α-Gal A enzyme activity and globotriaosylsphingosine (lyso-Gb3) biomarker assays from dried blood spots, as well as next-generation sequencing (NGS).&lt;/div&gt;&lt;div&gt;A total of 513 enzyme tests, 284 lyso-Gb3 tests, and 994 NGS tests were conducted on 1380 individuals (708 female, 661 male, 11 sex unknown) with clinical suspicion, or family history or abnormal newborn screening (NBS) results who participated in the project from December 2018–April 2023. Among these individuals, 21 % (103 male and 2 sex unknown) had abnormal α-Gal A levels (range 0.054–1.069 μM/h, normal level ≥ 1.10 μM/h), and 70 % (79 female, 115 male and 2 sex unknown) had elevated lyso-Gb3 levels (range 1.12–130.56 ng/mL, normal level ≤ 1.11 ng/mL). A total of 137 different reportable variants have been identified in this cohort including novel variants c.[351T&gt;G;361G&gt;C] (p.I117M;A121P), c.370-558_370-1del, c.548del, and c.1165C&gt;T (p.P389S).&lt;/div&gt;&lt;div&gt;All female patients with loss-of-function (LOF) variants and biomarker results were found to have elevated lyso-Gb3 levels. In contrast to those with LOF variants, females with missense &lt;em&gt;GLA&lt;/em&gt; variants had various lyso-Gb3 results. Pathogenic (P)/likely pathogenic (LP) missense variants [including c.1087C&gt;T (p.R363C), c.1088G&gt;A (p.R363H), c.593T&gt;C (p.I198T), c.644A&gt;G (p.N215S), c.335G&gt;A (p.R112H), c.337T&gt;C (p.F113L), and c.835C&gt;G (p.Q279E)] were identified in 16 female patients with normal lyso-Gb3 levels. These findings suggest that the use of lyso-Gb3 testing without &lt;em&gt;GLA&lt;/em&gt; sequencing may result in missed diagnosis in some female patients with FD missense variants.&lt;/div&gt;&lt;div&gt;Different biochemical and DNA variant profiles have been observed between NBS and non-NBS male patients. Among the non-NBS males, both enzyme and biomarker results correlate with age at the time of testing, which appear to be an approximated indicator for age of onset and disease severity. Among all the NBS males with both enzyme and lyso-Gb3 results, abnormal α-Gal A levels were found in all having P/LP variants except for the 11 who had c.427G&gt;A (p.A143T) or c.870G&gt;C (p.M290I), while normal lyso-Gb3 results have been found in many males with various P/LP variants – though it should of course be noted that lyso-Gb3 levels may increase over time. Our observation in NBS male patients may suggest that the enzyme test has a higher sensitivity, while lyso-Gb3 test has a higher specificity, and when combined with DNA test results, can provide a more comprehensive and reliable result.&lt;/div&gt;&lt;div&gt;This manuscript presents the largest-to-date, comprehensive, multi-testing Fabry cohort with demographic information and biochemical phenotypes from a sin","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 1","pages":"Article 109082"},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular chaperones in lysosomal storage diseases","authors":"Aslı İnci ,&nbsp;Serap Dökmeci","doi":"10.1016/j.ymgme.2025.109086","DOIUrl":"10.1016/j.ymgme.2025.109086","url":null,"abstract":"<div><div>Lysosomal storage disorders (LSDs) are a diverse group of inherited metabolic disorders characterized by the accumulation of undegraded substrates within lysosomes due to defective lysosomal function. Recent research has highlighted the pivotal role of extracellular chaperones in the pathophysiology of LSDs, revealing their crucial involvement in modulating disease progression. These chaperones aid in stabilizing and refolding misfolded lysosomal enzymes, enhancing their proper trafficking and function, which in turn reduces substrate accumulation. Furthermore, extracellular chaperones have emerged as promising biomarkers, with their levels in bodily fluids offering potential for disease diagnosis and monitoring. This review explores the current understanding of extracellular chaperones in the context of LSDs, examining their mechanisms of action, biomarker and therapeutic potential, and future directions in clinical application of LSDs.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 1","pages":"Article 109086"},"PeriodicalIF":3.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early postnatal hepatocyte transplantation in a child with molybdenum cofactor deficiency type B","authors":"A. Selvanathan ,&nbsp;I. Kankananarachchi ,&nbsp;S. Bansal ,&nbsp;E. Fitzpatrick ,&nbsp;H. Lemonde ,&nbsp;C. Turner ,&nbsp;L. Fairbanks ,&nbsp;F.J. White ,&nbsp;A. Dhawan ,&nbsp;B.C. Schwahn","doi":"10.1016/j.ymgme.2025.109079","DOIUrl":"10.1016/j.ymgme.2025.109079","url":null,"abstract":"<div><div>Molybdenum cofactor deficiencies (MoCD) are a group of inborn errors of metabolism that result in impaired synthesis of molybdenum cofactor, crucial for the function of three oxidases (sulfite oxidase, xanthine oxidase and aldehyde oxidase). Most patients present with severe neonatal-onset epileptic encephalopathy, hypotonia, poor feeding and apnoea, with death typically occurring within the first three years of life. Whilst there is now an emerging therapy for MoCD Type A (cPMP/fosdenopterin), this treatment is not effective for MoCD Type B and there is no treatment for isolated sulfite oxidase deficiency (ISOD). Liver directed gene delivery is a potential alternative therapy for sulfite intoxication disorders.</div><div>We report an attempt to use hepatocyte transplantation as a treatment option for MoCD Type B, in an infant with a strong family history of neonatal-onset disease and early mortality. Six transfusions of hepatocytes were given between Day 1 and Day 18 of life, totalling around 1 × 10⁹ cells with immunosuppressive cover. Concomitantly dietary protein restriction was maintained at 2 g/kg, including 0.7 g/kg of methionine- and cyst(<em>e</em>)ine-free amino acid mixture. The aim was to utilize hepatocyte transplantation as a bridge to liver transplantation.</div><div>Whilst there was evidence of biochemical stabilization with reduction in concentrations of sulfite and S-sulfocysteine and a moderate increase in urate levels compared to the sibling, the treatment was not able to prevent acute brain injury from sulfite toxicity which was evident in neuroimaging at 35 h of age. This correlated clinically with ongoing seizures as well as minimal developmental progress.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 1","pages":"Article 109079"},"PeriodicalIF":3.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acid sphingomyelinase deficiency: Laboratory diagnosis, genetic and epidemiologic aspects of a 50-year French cohort","authors":"Roseline Froissart ,&nbsp;Magali Pettazzoni ,&nbsp;Cécile Pagan ,&nbsp;Thierry Levade ,&nbsp;Marie T. Vanier","doi":"10.1016/j.ymgme.2025.109081","DOIUrl":"10.1016/j.ymgme.2025.109081","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;Laboratory diagnosis of acid sphingomyelinase (ASM) deficiency (ASMD) was implemented in France in the early 1970s. The aims of this study were (i) to review the combined use of successively developed strategies - enzyme measurement, genetic testing, and biomarkers analysis – and (ii) to describe the mutational spectrum and epidemiological characteristics of a large patient cohort followed in French hospitals.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;During the 1974–2023 period, 271 patients with ASMD (238 families) were diagnosed. The chronic visceral form (historical Niemann-Pick type B) constituted 68 % of the cases, the infantile neurovisceral (type A) form 23 %, and the chronic neurovisceral (type AB) form 9 %. Profoundly deficient ASM activities were constantly observed in the neuronopathic forms. Elevated plasma concentrations of LysoSM and LysoSM-509/PPCS proved useful to comfort interpretation of ASM activities near cut-off found in leukocytes or dried blood spots of some patients with ASMD type B. Although not specific, LysoSM-509/PPCS appeared as the most sensitive biomarker. The spectrum of &lt;em&gt;SMPD1&lt;/em&gt; variants was investigated in 183 families. A total of 93 different &lt;em&gt;SMPD1&lt;/em&gt; variants (26 novel ones) was identified (58 % missense, 19 % frameshift, and 12 % nonsense ones). The proportion of null variants was much larger in ASMD type A (63 %) than in type B (24 %). In type AB, c.1177 T &gt; G (p.Trp393Gly) contributed 32 % of the mutant alleles, most patients having Romani or Northwestern-Balkanic roots, while c.880C &gt; A (p.Gln294Lys) only accounted for 9 %. Homoallelic variants in neuronopathic patients allowed genotype/phenotype correlations. In type B, c.1829_1831delGCC (p.Arg610del) represented 57 % of alleles, with a wide diversity of other variants. Among type B families, approximately one-third had a North African origin, and this variant accounted for 91 % alleles in this subgroup, compared to 40 % in non-North-African families. In patients homozygous for p.Arg610del (&lt;em&gt;n&lt;/em&gt; = 69), the age at biological diagnosis was significantly higher (34.0 years; IQR 7.4–45.3) than in patients with either one (&lt;em&gt;n&lt;/em&gt; = 41) [4.3 years; IQR 2.77–18.30] or no such allele (&lt;em&gt;n&lt;/em&gt; = 43) [6.3 years; IQR 2.2–31.7]. A further observation was the proportional increase in the number of type B patients diagnosed after the age of 30 years since 2015. This nearly complete national cohort allowed a tentative evaluation of (minimal) incidences at birth as follows: ASMD (all clinical forms): 0.70/100,000; type B: 0.48/100,000; neuronopathic types (A and AB): 0.22/100,000.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This comprehensive cohort (i) summarizes the real-life experience of laboratory diagnosis of ASMD in two expert centres, (ii) confirms the high frequency of the p.Arg610del allele in France and discloses some characteristics of patients homozygous for this variant; (iii) provides for the first time d","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 1","pages":"Article 109081"},"PeriodicalIF":3.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using multiple modalities to confirm diagnosis in patients with suspected peroxisome biogenesis disorders","authors":"Anthony C.T. Cheung ,&nbsp;Erminia Di Pietro ,&nbsp;Catherine Argyriou ,&nbsp;Eric Bareke ,&nbsp;Yasmin D'Souza ,&nbsp;Ratna Dua Puri ,&nbsp;P. Muhammed Shabeer ,&nbsp;Rebecca Ganetzky ,&nbsp;Amy Goldstein ,&nbsp;Adeline Vanderver ,&nbsp;Shruthi Mohan ,&nbsp;Jacek Majewski ,&nbsp;Christine Yergeau ,&nbsp;Nancy Braverman","doi":"10.1016/j.ymgme.2025.109080","DOIUrl":"10.1016/j.ymgme.2025.109080","url":null,"abstract":"<div><div>Zellweger spectrum disorder (ZSD) results from biallelic variants in any one of 13 <em>PEX</em> genes involved in peroxisome biogenesis and function. The majority of ZSD cases result from pathogenic variants in <em>PEX1</em>. Here, we present 3 patients with suspected <em>PEX1</em>-related ZSD and non-diagnostic whole exome sequencing and describe the use of multiple modalities to ascertain their diagnosis. We confirmed peroxisomal dysfunction in the patients by demonstrating abnormal peroxisome metabolite levels in blood and peroxisome import dysfunction in patient fibroblasts. RNA studies including RNA-seq and RT-PCR, followed by Sanger sequencing showed leaky splice variants including an intron 13 variant causing exon 14 skipping (Patient 1), an intron 22 variant causing intron 22 retention (Patient 2), and a synonymous splice-site variant causing exon 16 skipping (Patient 3). All three patients had very low amounts of canonical PEX1 transcripts on RNA-seq, as well as residual but reduced PEX1 protein levels on immunoblotting, which likely explains their non-severe ZSD phenotype. This study suggests that a multi-modality approach combining biochemical testing, functional assays in fibroblasts and molecular investigations including sequencing of non-coding regions and RNA analysis may aid in diagnosis of patients with suspected PBD-ZSD and inconclusive WES.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 1","pages":"Article 109080"},"PeriodicalIF":3.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Argentine program of home infusions with enzyme replacement therapy for lysosomal diseases: Results in safety, quality of life and adherence","authors":"Guillermo Drelichman ,&nbsp;Juan M. Politei ,&nbsp;Nicolás Fernandez Escobar ,&nbsp;Barbara Soberón ,&nbsp;Nora Basack ,&nbsp;Norberto Guelbert ,&nbsp;Nora Watman ,&nbsp;Norberto Antongiovanni ,&nbsp;Fernanda Cuello ,&nbsp;Gerardo Mogni ,&nbsp;María Larroude ,&nbsp;Gabriel Aguilar ,&nbsp;Paola Reichel ,&nbsp;Alberto Dubrovsky ,&nbsp;Gustavo Cabrera ,&nbsp;Adriana Arizo ,&nbsp;Marcela Corrales ,&nbsp;Adriana Degano ,&nbsp;Alejandro Faimboin ,&nbsp;Analía Carvani ,&nbsp;Fernando Perretta","doi":"10.1016/j.ymgme.2025.109076","DOIUrl":"10.1016/j.ymgme.2025.109076","url":null,"abstract":"<div><div>With over 25 years of experience, enzyme replacement therapies have proven to be safe and effective for patients with Fabry, Gaucher, Pompe, Mucopolysaccharidosis I (MPS I) diseases. As with many chronic conditions, one of the keys to achieving therapeutic goals is to avoid interruptions in infusions to ensure proper adherence (AD). Treatment interruptions are associated with the recurrence of previously resolved clinical manifestations depending on the length of the interruption, and the reaccumulation of substrate at the cellular level. The Argentine home infusion program (HI) was established in 2012 in response to recognizing low treatment adherence. This is a retrospective review of the program's safety, quality of life, and treatment adherence after 11 years. A total of 147 treating physicians enrolled 378 patients from 22 Argentine provinces into the program. A total of 85,060 home infusions were performed during the study period. No patients experienced serious adverse events requiring hospitalization. Throughout the follow-up period, 21,600 infusions were suspended, with the most frequent cause being lack of supply from the payer. Adherence to enzyme replacement therapy showed an annual adherence rate of over 80 % across all pathologies. All patients (100 %) reported that the program had improved their quality of life. The Argentine home infusion program has demonstrated an improvement in adherence and quality of life, which is considered significant for enhancing long-term therapeutic outcomes.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 1","pages":"Article 109076"},"PeriodicalIF":3.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal health outcomes in ornithine transcarbamylase deficiency: A comparative analysis of pregnancies in symptomatic and asymptomatic heterozygotes","authors":"Margo Sheck Breilyn ,&nbsp;Kara Simpson ,&nbsp;Sara A. Elsbecker ,&nbsp;John R. Barber ,&nbsp;Members of the Urea Cycle Disorders Consortium (UCDC),&nbsp;Kia Bryan ,&nbsp;Susan A. Berry","doi":"10.1016/j.ymgme.2025.109083","DOIUrl":"10.1016/j.ymgme.2025.109083","url":null,"abstract":"<div><h3>Introduction</h3><div>Ornithine transcarbamylase deficiency (OTCD, MIM: <span><span>311250</span><svg><path></path></svg></span>) is an X-linked disorder of ureagenesis caused by pathogenic variants in <em>OTC</em> (MIM: <span><span>300461</span><svg><path></path></svg></span>). Due to varying X-inactivation patterns, female heterozygotes can range from asymptomatic to severe disease with recurrent hyperammonemia.</div><div>There is a paucity of data regarding the safety of pregnancy in symptomatic versus asymptomatic OTC heterozygotes. Existing case reports suggest a high risk of morbidity and mortality associated with pregnancy.</div></div><div><h3>Materials and methods</h3><div>This study investigated the maternal health outcomes from a large cohort of OTC heterozygote participants who were enrolled in a multicenter, observational, natural history study conducted by the Urea Cycle Disorders Consortium.</div></div><div><h3>Results</h3><div>We evaluated maternal morbidity and mortality from 109 pregnancies in 49 OTC heterozygotes and found that pregnancy was well-tolerated without metabolic decompensations in individuals with asymptomatic OTCD. Thirty-one participants (63.3 %) had a second pregnancy. Among individuals with symptomatic disease, hyperammonemia was observed in 5 of the 21 pregnancies. Three of these episodes were in a single individual across three different pregnancies. One individual required ICU admission. There was no maternal mortality in either group.</div></div><div><h3>Conclusions</h3><div>Our results indicate that pregnancy is well-tolerated in asymptomatic OTC heterozygotes, with no metabolic decompensations observed. Close monitoring with a metabolic center is strongly recommended for OTC heterozygotes in pregnancy, in particular for symptomatic individuals to mitigate the risk of metabolic decompensation.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"144 4","pages":"Article 109083"},"PeriodicalIF":3.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Pompe disease: Unmet needs and emerging therapies” [Mol Genet Metab. 2024 Nov;143(3):108590]","authors":"Kelly A. George,&nbsp;Allyson L. Anding,&nbsp;Arjan van der Flier,&nbsp;Giulio S. Tomassy,&nbsp;Kenneth I. Berger,&nbsp;Tracy Y. Zhang,&nbsp;S. Pablo Sardi","doi":"10.1016/j.ymgme.2025.109078","DOIUrl":"10.1016/j.ymgme.2025.109078","url":null,"abstract":"","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"144 4","pages":"Article 109078"},"PeriodicalIF":3.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}