Molecular Genetics and Metabolism Reports最新文献

{"title":"Outcome of creatine supplementation therapy in phosphoglucomutase-1 deficiency associated congenital disorders of glycosylation: Novel insights","authors":"Anastasia Ambrose ,&nbsp;Morganne McCabe ,&nbsp;Clara Hung ,&nbsp;Iveta Sosova ,&nbsp;Peter Seres ,&nbsp;Saadet Mercimek-Andrews","doi":"10.1016/j.ymgmr.2025.101212","DOIUrl":"10.1016/j.ymgmr.2025.101212","url":null,"abstract":"<div><h3>Background</h3><div>Biallelic pathogenic variants in <em>PGM1</em> result in phosphoglucomutase 1 (PGM1) deficiency that is one of the congenital disorders of glycosylation (CDG) (PGM1-CDG). Phenotypic spectrum includes congenital malformations, and muscular, cardiac, hepatic, endocrine and hematologic phenotypes. Current treatment consists of D-galactose therapy that results in clinical and biochemical improvements. To improve fatigue, and exercise intolerance, we started creatine supplementation therapy.</div></div><div><h3>Material and methods</h3><div>We reviewed electronic patient chart. We applied Nijmegen Pediatric CDG Rating Scale (NPCRS) and The Functional Assessment of Chronic Illness Therapy Fatigue scale (FACIT-F). We measured creatine metabolism biomarkers.</div></div><div><h3>Results</h3><div>This is a 29-year-old female with PGM1-CDG, confirmed diagnosis by clinical exome sequencing. She has been treated with D-galactose therapy which did not improve her fatigue and exercise intolerance. She was started on creatine supplementation therapy at the age of 27 years which led to decreased daytime sleeping, increased exercise capacity and improvements in her NPCRS, and FACIT-F. Her plasma guanidinoacetate was low. She had elevated urine galactitol on D-galactose therapy.</div></div><div><h3>Discussion</h3><div>PGM1-CDG associated myopathy is likely due to combination of several factors including abnormal muscle carbohydrate metabolism, abnormal N-glycosylation of proteins involved in the muscle functions and creatine transport and altered muscle energy homeostasis. It was previously shown that creatine supplementation therapy improves myopathy in patients with mitochondrial cytopathies. We think that the use of creatine supplementation therapy coincided with improvements in fatigue and exercise intolerance subjectively and objectively in our patient.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101212"},"PeriodicalIF":1.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768682","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":"Benefits of early intervention with olipudase alfa in symptomatic children with acid sphingomyelinase deficiency: A sibling case-comparison study","authors":"Drew B. Sinha ,&nbsp;William L. Simpson ,&nbsp;Andrew Ting ,&nbsp;Louise Bier ,&nbsp;Mary Freeman ,&nbsp;Lauren Mackenzie Mason ,&nbsp;George A. Diaz ,&nbsp;Jaya Ganesh","doi":"10.1016/j.ymgmr.2025.101210","DOIUrl":"10.1016/j.ymgmr.2025.101210","url":null,"abstract":"<div><div>Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease with multisystem complications including neurodegeneration, hepatosplenomegaly, interstitial lung disease (ILD), bone marrow disease, and growth failure. Non-neurological manifestations of this disease are amenable to enzyme replacement therapy (ERT) with olipudase alfa in both adult and pediatric patients. In this study, we offer evidence for the role of intervention in early childhood pediatric cases. We present longitudinal follow-up for two siblings with ASMD (<em>SMPD1</em> p.R498L/p.R610del compound heterozygous genotype) who were started on ERT at different ages (ages 3 and 7, duration of treatment &gt;4 years). After initiation of ERT, both siblings demonstrated significant radiographic improvement of interstitial lung disease (ILD), organomegaly, and growth. Notably, the younger sibling who had started earlier on treatment did not experience any deceleration in growth parameters and has normal height and weight for age, while the older sibling showed a decline in growth velocity that improved once treatment was initiated. Similarly, the older sibling showed similar-to-worse ILD and more persistent organomegaly compared to the younger sibling. Treatment has resulted in sustained improvements in both patients. These findings suggest that early intervention with ERT in ASMD may have cumulative benefits for pediatric health and motivate early screening for ASMD in pediatric patients.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101210"},"PeriodicalIF":1.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759504","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":"Atypical case of neonatal-onset Gaucher disease type 3b: A case report","authors":"Takanori Onuki ,&nbsp;Kinuko Kojima ,&nbsp;Kentaro Sawano ,&nbsp;Nao Shibata ,&nbsp;Yohei Ogawa ,&nbsp;Go Hasegawa ,&nbsp;Aya Narita ,&nbsp;Hiromi Nyuzuki","doi":"10.1016/j.ymgmr.2025.101211","DOIUrl":"10.1016/j.ymgmr.2025.101211","url":null,"abstract":"<div><div>Neonatal-onset Gaucher disease (nGD) is considered perinatal lethal GD, a variant of GD type 2 (GD2), and is associated with collodion skin or hydrops fetalis, hepatosplenomegaly, and involvement of central nervous system (CNS). Pulmonary involvement (PI) and lymphadenopathy (LD) are reported GD complications and have unknown incidence, pathogenesis, and response to treatments. Here, we report the case of a patient diagnosed with nGD with collodion skin who developed only mild neurological symptoms and later died in early childhood due to treatment-resistant PI and LD. A female neonate was born at 38 weeks of gestation (weight: approximately 2012 g, height: 45 cm). She had a collodion skin, hepatosplenomegaly, hemorrhagic plaques, and cholestatic liver disease at birth. She was diagnosed with GD based on decreased glucocerebrosidase enzyme activity, and genetic analysis of <em>GBA1</em> revealed compound heterozygous mutations of c.1193G &gt; T (p.Arg398Leu) and c.1265_1319del (p.Leu422fs). Intravenous enzyme replacement therapy (ERT) was initiated at the 15 days of age. At the age of 2 years and 2 months, she had a Developmental Quotient of 88 but developed horizontal gaze palsy. At 2 years 8 months of age, she developed mesenteric LD and PI because of which she failed to gain weight and developed tachypnea. She was started on oxygen therapy but died of respiratory failure and malnutrition due to PI and LD at the age of 3 years and 8 months. Pathological autopsy did not reveal the presence of Gaucher cells (GCs) in the liver, spleen, and bone marrow, but all lung macrophages had been transformed to GCs that were draining the alveoli, LD was observed in the mesenteric and mediastinal lymph nodes, and nodules of GCs were formed in bilateral kidneys. In conclusion, nGD with collodion skin is not always classified GD2. Although her phenotype may be classified as GD3b, her clinical course was like severe GD1. In addition, PI and LD are difficult to treat with adequate ERT.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101211"},"PeriodicalIF":1.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The precise molecular diagnosis of novel GLDC compound heterozygous variants highlights the benefits for a Chinese family with nonketotic hyperglycinemia","authors":"Fang Yuan ,&nbsp;Xiaozhen Song ,&nbsp;Rongrong Yin ,&nbsp;Xiaoping Lan ,&nbsp;Jingjing Sun ,&nbsp;Xiaojun Tang ,&nbsp;Wuhen Xu ,&nbsp;Shaohua Hu ,&nbsp;Man Xiao ,&nbsp;Hong Zhang ,&nbsp;Wenhao Weng ,&nbsp;Yuanfeng Zhang ,&nbsp;Shengnan Wu","doi":"10.1016/j.ymgmr.2025.101209","DOIUrl":"10.1016/j.ymgmr.2025.101209","url":null,"abstract":"<div><div>Glycine encephalopathy, also known as nonketotic hyperglycinemia (NHK), is a rare inherited disease caused by an inborn error of glycine metabolism, resulting in elevated glycine concentration in plasma and cerebrospinal fluid. Clinical manifestations mainly include varying degrees of hypotonia, apneic episodes, epilepsy, psychomotor delay during the neonatal period or early infancy. Biallelic variants in <em>GLDC</em> account for up to 80 % of classical NKH cases. Here we describe the clinical, biochemical, and molecular characteristics of two Chinese siblings with severe NHK. Their phenotypes included severe symptoms in neonatal period, seizures, and psychomotor delay. The siblings carry novel compound heterozygous variants in <em>GLDC</em>, c.1740C &gt; G (p.His580Gln) and c.1023G &gt; A (p.Val341=). Based on previous literature reports and pathogenicity prediction, the c.1740C &gt; G (p.His580Gln) variant is classified as likely pathogenic. By minigene analysis, we confirmed the synonymous mutation c.1023G &gt; A (p.Val341=) led to abnormal splicing, with 38 bp missing in exon 7 in the <em>GLDC</em> gene. These findings highlight the pathogenic nature of a novel synonymous mutation c.1023G &gt; A, expand the genetic spectrum of <em>GLDC</em> and provide crucial guidance for both the patient's clinical management and family's reproductive genetic counseling.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101209"},"PeriodicalIF":1.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696807","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":"Identification of novel variants in carbamoyl phosphate synthetase 1 gene and comparative pathogenicity assessments of CPS1 missense variants following ACMG/AMP-ClinGen recommendation for computational tools","authors":"Fei Li ,&nbsp;Qin Cai ,&nbsp;Wei Ji ,&nbsp;Miao Xu ,&nbsp;Guoli Tian ,&nbsp;Fanyi Zeng","doi":"10.1016/j.ymgmr.2025.101208","DOIUrl":"10.1016/j.ymgmr.2025.101208","url":null,"abstract":"<div><div>Carbamoyl phosphate synthetase I (CPS1) deficiency is a rare autosomal recessive metabolic abnormality cause by dysfunctionality of CPS1 and often result in unfavorable outcome. In this study, we presented the detailed laboratory features and genetic analysis of two patients with heterozygous variants of CPS1, c.1927 A &gt; G (p.Asn643Asp), c.2375 T &gt; G (p.Met792Arg), c.3443 T &gt; A (p.Met1148Lys) in patient 1; c.3784C &gt; T (p.Arg1262Ter), c.3734 T &gt; A (p.Leu1245His) in patient 2, respectively. c.1927 A &gt; G (p.Asn643Asp) and c.2375 T &gt; G (p.Met792Arg) are novel out of 5 variants and classified as variants of uncertain significance (VUS) under the guidelines of ACMG/AMP-ClinGen. Structure-based analysis of 4 missense variants indicates deleterious alterations to the protein. Since the employment of genetic testing as a clinical diagnostic tool, distinguishing pathogenic from polymorphic changes poses significant problems for geneticists. As recommendation for PP3/BP4, the computational tools for missense variant have been published, we performed a comparative evaluation for pathogenicity interpretation in our patients and in ClinVar database regarding CPS1 missense variants under the updated guidelines of ACMG/AMP-ClinGen. The application of computational tools under the ACMG/AMP-ClinGen criteria revealed an increased sensitivity for pathogenicity evaluation, from variants of uncertain significance (VUS) to likely pathogenic (LP) in previously reported cases; while for variants without clinic information in the ClinVar database, the pathogenicity assessment of VUS remained, and shows a more optimistic and reliable clinical application in molecular diagnosis.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101208"},"PeriodicalIF":1.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685375","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":"Successful desensitization protocol to alglucosidase and avalglucosidase alfa in a patient with infantile-onset Pompe disease","authors":"Miriam Gendive ,&nbsp;Teresa C. Delgado ,&nbsp;María Unceta ,&nbsp;Arantza Arza ,&nbsp;Beatriz Sordo ,&nbsp;Aritza Segurola ,&nbsp;Javier De las Heras","doi":"10.1016/j.ymgmr.2025.101207","DOIUrl":"10.1016/j.ymgmr.2025.101207","url":null,"abstract":"<div><div>Infantile-onset Pompe disease is a lysosomal disease characterized by cardiomyopathy and muscle weakness that, without specific treatment, is fatal within the first two years of life. We present the case of an infant who developed anaphylaxia to enzyme replacement therapy with alglucosidase-alfa. We provide a desensitization protocol to alglucosidase-alfa and, for the first time, a desensitization protocol to avalglucosidase-alfa, both delivered in a reasonable time of &lt;6 h, and without any further reactions in the patient.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101207"},"PeriodicalIF":1.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685376","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":"FBXL4-related encephalomyopathic mitochondrial DNA depletion syndrome: A rare cause of hyperammonemia","authors":"Ayça Burcu Kahraman ,&nbsp;Halil Çelik ,&nbsp;Zafer Bagci ,&nbsp;Abdullah Sezer ,&nbsp;Mustafa Kılıç","doi":"10.1016/j.ymgmr.2025.101206","DOIUrl":"10.1016/j.ymgmr.2025.101206","url":null,"abstract":"<div><h3>Introduction</h3><div>FBXL4- related encephalomyopathic mitochondrial DNA (mtDNA) depletion syndrome is caused by pathogenic variants in the <em>FBXL4</em> gene, resulting in mitochondrial dysfunction and multisystem involvement. Hyperammonemia is reported in 45 % of cases but extremely elevated ammonia levels are rare.</div></div><div><h3>Case presentation</h3><div>A male infant presented with dysmorphic features, hypotonia, failure to thrive, and lactic acidosis and severe hyperammonemia (ammonia: 1495 μmol/L). Genetic testing identified a homozygous <em>FBXL4</em> pathogenic variant.</div></div><div><h3>Conclusion</h3><div>To our knowledge, this report presents a neonatal case of FBXL4-related mtDNA depletion syndrome with the highest hyperammonemia level. This case emphasizes the importance of <em>FBXL4</em> genetic testing in neonates with multisystem involvement, hyperammonemia, and dysmorphic features.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101206"},"PeriodicalIF":1.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628615","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":"An 18-month-old girl with Vici syndrome: A case report study","authors":"Parsa Forouhar ,&nbsp;Mohammad Amin Eghtedari ,&nbsp;Maryam Taraz ,&nbsp;Mahsa Abdullahpour ,&nbsp;Mohammad Mehrpouyan ,&nbsp;Zhale Askarzade","doi":"10.1016/j.ymgmr.2025.101205","DOIUrl":"10.1016/j.ymgmr.2025.101205","url":null,"abstract":"<div><div>We report an 18-month-old female diagnosed with Vici syndrome, a rare congenital disorder characterized by developmental delay, albinism, cataracts, agenesis of the corpus callosum, hypotonia, and immunological anomalies. The patient, the second child of healthy first-cousin parents, presented with hypotonia at birth and subsequently developed bilateral cataracts, feeding difficulties, and multiple systemic manifestations, including kidney, bladder, and gallstones, as well as cardiomegaly and seizures. Genetic testing identified homozygous mutations in the EPG5 gene, confirming the diagnosis of Vici syndrome. The cardiac evaluation revealed a unique finding: serial echocardiograms initially detected multiple masses, which later regressed spontaneously, suggestive of a cardiac rhabdomyoma.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101205"},"PeriodicalIF":1.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611308","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 novel SLC44A gene variant in a patient with neonatal cholestasis and liver failure","authors":"Dogan Barut ,&nbsp;Emine Burçe Dörtkardeşler ,&nbsp;Miray Karakoyun ,&nbsp;Ebru Canda ,&nbsp;Huseyin Onay ,&nbsp;Sema Aydogdu","doi":"10.1016/j.ymgmr.2025.101204","DOIUrl":"10.1016/j.ymgmr.2025.101204","url":null,"abstract":"<div><div><em>SLC44A1</em> gene variants (MIM # 618868) are associated with a choline transporter deficiency with a rare autosomal recessive genetic disorder characterized by neurodegeneration, childhood-onset with ataxia, tremor, optic atrophy, and cognitive decline. Variants in the <em>SLC44A1</em> gene are considered to be responsible for the syndrome. We reported a four-month-old baby with neonatal cholestasis and liver failure, but neurological development and examination were normal. During the patient's initial physical examination, height, weight, and head circumference were &lt; −2 SDS. He was alert, with eye tracking and a smile present, appeared icteric, and exhibited hepatosplenomegaly, with a history of second-degree consanguinity between his parents. The patient showed signs of neonatal jaundice, elevated transaminases, and episodes of hypoglycemia. After excluding biliary atresia, tyrosinemia, and other metabolic diseases, mitochondrial hepatopathy, vascular pathologies, and congenital infectious diseases through all standard examinations for neonatal cholestasis, a genetic analysis test and whole exome analysis were conducted. Molecular analysis of the whole exome revealed a novel inherited mutation, one inherited from each parent. This novel variant in the SLC44A1 gene is c.1632 + 1G &gt; A. A thorough physical examination and laboratory tests should be conducted for patients presenting with neonatal cholestasis. Subsequently, whole exome analysis from the parents identified the same mutation as heterozygous c.1632 + 1G &gt; A in the SLC44A1 gene. Genetic examinations should be considered in patients whose cause remains undetermined, particularly when there is a family history.</div></div><div><h3>Conclusion</h3><div>We describe a novel childhood-onset liver failure and metabolic disease caused by choline transporter deficiency with autosomal recessive inheritance.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101204"},"PeriodicalIF":1.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592980","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":"Carbamoyl phosphate synthetase 1 deficiency manifested in an adult treated with prednisone for polymyositis, and cured by live-donor liver transplantation","authors":"Kazuhiro Yokota ,&nbsp;Akira Ohtake ,&nbsp;Taro Yamazaki ,&nbsp;Takuma Tsuzuki-Wada ,&nbsp;Megumi Saito-Tsuruoka ,&nbsp;Takuya Fushimi ,&nbsp;Kei Murayama ,&nbsp;Yuji Akiyama ,&nbsp;Toshihide Mimura","doi":"10.1016/j.ymgmr.2025.101200","DOIUrl":"10.1016/j.ymgmr.2025.101200","url":null,"abstract":"<div><div>Carbamoyl phosphate synthetase 1 (CPS1) deficiency (OMIM#<span><span>237300</span><svg><path></path></svg></span>) is a rare inherited disorder due to complete or partial lack of the CPS1 enzyme. Polymyositis is a relatively rare systemic inflammatory autoimmune disease. Here, we report a 59-year-old Japanese woman diagnosed with late-onset CPS1 deficiency during polymyositis treatment. The polymyositis appeared two years before the diagnosis of CPS1 deficiency. Prednisolone (PSL) at 35 mg/day initial dosage, promptly alleviated the symptoms. However, the patient, without apparent cause, suddenly developed confusion progressing to unconsciousness and coma. Upon admission, the patient’s plasma ammonia levels were 458 μg/dL (269 μM). Plasma amino acid analysis revealed decreased citrulline levels and elevated glutamine levels. Genetic analysis of <em>CPS1</em> (OMIM *608307) showed homozygosity for the likely pathogenic variant c.2397G &gt; A (p.Met799Ile), leading to the diagnosis of CPS1 deficiency. The patient responded to pharmacotherapy and continuous hemodialysis. However, the patient experienced hyperammonemia decompensation events while on pharmacotherapy at home, which were successfully managed with emergency treatment and/or hemodialysis. Subsequently, after liver transplantation, the patient's plasma ammonia levels consistently remained at normal. This case illustrates late-onset CPS1 deficiency manifested in an adult treated with PSL for polymyositis, and the cure of its enzyme deficiency by live-donor liver transplantation.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"43 ","pages":"Article 101200"},"PeriodicalIF":1.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549698","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}