Molecular genetics and metabolism最新文献

{"title":"Expansion of genotype/phenotype correlation in an individual with compound heterozygous variants in CYP51A1 and congenital cataract","authors":"Maxwell B. Colonna ,&nbsp;Andrzej B. Poplawski ,&nbsp;Marie N. Brzoska ,&nbsp;Dionne Le ,&nbsp;Natasha L. Rudy ,&nbsp;Kameryn M. Butler ,&nbsp;Wesley G. Patterson ,&nbsp;Camerun C. Washington ,&nbsp;Elliot Stolerman ,&nbsp;Libin Xu ,&nbsp;Gavin Arno ,&nbsp;Richard Steet","doi":"10.1016/j.ymgme.2025.109230","DOIUrl":"10.1016/j.ymgme.2025.109230","url":null,"abstract":"<div><div>Numerous genetic conditions are represented within the biochemical pathway for de novo cholesterol biosynthesis. Among the emerging disease-gene associations is <em>CYP51A1</em>, encoding a lanosterol demethylase enzyme. Biallelic variants in <em>CYP51A1</em> have been associated with congenital cataracts and variable liver disease but an appreciation of genotype/phenotype correlation is lacking due to the limited number of patients described. Here we report a 21 month-old female with congenital cataracts harboring compound heterozygous variants of uncertain significance in <em>CYP51A1</em>. Functional studies were performed to resolve the impact of these variants, demonstrating effects at the both the transcript and protein level, and clear evidence of pathogenicity. Molecular analysis of primary lymphoblastoid cells from the proband revealed defects in transcript expression, reduced protein abundance, and a loss of enzymatic function resulting in lanosterol accumulation and increased sensitivity to ferroptosis. These data provide supporting evidence of the association between <em>CYP51A1</em> defects and congenital cataract that will aid in further establishing a genotype/phenotype correlation.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"146 1","pages":"Article 109230"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987934","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":"Identification of 13 novel pathogenic SLC25A13 variants and comparison of the genetic spectrum among different geographic regions: Molecular characterization of a large cohort of citrin deficiency in China","authors":"Rui-Lan Cheng ,&nbsp;Jian-Wu Qiu ,&nbsp;Qin Zhou ,&nbsp;Joseph Hong Saberon ,&nbsp;Jian Shi ,&nbsp;Mei Deng ,&nbsp;Li Guo ,&nbsp;Feng-Ping Chen ,&nbsp;Wei-Xia Lin ,&nbsp;Yuan-Zong Song","doi":"10.1016/j.ymgme.2025.109238","DOIUrl":"10.1016/j.ymgme.2025.109238","url":null,"abstract":"<div><h3>Objective</h3><div>Citrin deficiency (CD), caused by biallelic pathogenic variants in <em>SLC25A13</em>, remains underdiagnosed due to allelic heterogeneity, variants of uncertain significance (VUS), and technical limitations. This study aimed to improve the diagnosis of CD by identifying novel pathogenic <em>SLC25A13</em> variants and characterizing the variant spectrum and geographic distribution in a large Chinese pediatric cohort.</div></div><div><h3>Methods</h3><div>Polymerase chain reaction (PCR)-based methods and Sanger sequencing were performed to identify pathogenic <em>SLC25A13</em> variants in 220 pediatric patients with clinically suspected CD and their parents from 2016 to 2024. We functionally validated novel missense and splice-site variants using agc1-knockout yeast modeling and minigene assays, respectively. Data from these 191 newly diagnosed CD patients (2016–2024) were combined with data from 274 previously reported CD cases (2005–2016) and from 186 additional CD patients diagnosed via next-generation sequencing since 2016. The <em>SLC25A13</em> variant spectrum and geographic distribution were then analyzed in this combined cohort. Statistical analyses were performed using Chi-square/Fisher's exact tests and one-way analysis of variance, as appropriate.</div></div><div><h3>Results</h3><div>A large cohort of 651 CD patients was assembled, and 13 novel pathogenic <em>SLC25A13</em> variants were identified, including c.177_189del, c.188del, c.212 + 3 A &gt; G, c.889G &gt; T, c.1193 T &gt; A, c.1210G &gt; T, c.1352 T &gt; A, c.1620del, c.1722del, c.1799_1800insAAA, c.1853_1855dup, c.1603_1609dup, and c.819-16 T &gt; A. The most frequent variants were c.852_855del (57.56 %), c.1751-5_1751–4ins(2684) (10.06 %), c.1638_1660dup (8.42 %), and c.615 + 5G &gt; A (7.93 %). The variant c.329-3_329-2ins(6072) ranked fifth at 2.13 %. In the Chinese mainland, the variant c.852_855del was most prevalent in southern and southwestern provinces, c.1638_1660dup was enriched in eastern coastal regions, and c.1751-5_1751–4ins(2684) reached its highest frequency in Sichuan Province (29.7 %).</div></div><div><h3>Conclusions</h3><div>The study established the largest CD cohort to date, expanded the <em>SLC25A13</em> variant spectrum, and delineated the distinct geographic distribution of these variants. These findings refined diagnostic protocols and emphasized the necessity for population-tailored genetic screening to optimize early diagnosis of CD.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"146 1","pages":"Article 109238"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117813","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":"TPI deficiency: A case report and review of the literature","authors":"Aaron Williams ,&nbsp;Monika Weisz-Hubshman ,&nbsp;Vittoria Rossi ,&nbsp;Emily Bland ,&nbsp;Elizabeth Mizerik ,&nbsp;Xi Luo ,&nbsp;Paul R. Hillman ,&nbsp;Kathleen Shields ,&nbsp;Fernando Scaglia","doi":"10.1016/j.ymgme.2025.109227","DOIUrl":"10.1016/j.ymgme.2025.109227","url":null,"abstract":"<div><div>Triosephosphate isomerase (TPI) is a ubiquitously expressed enzyme encoded by the <em>TPI1</em> gene. It catalyzes the interconversion of the triose phosphate isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate in the fifth step of glycolysis. TPI deficiency (TPI Df; MIM# <span><span>615512</span><svg><path></path></svg></span>) is an autosomal recessive disorder due to biallelic pathogenic variants in <em>TPI1</em>. In keeping with other glycolytic enzymopathies, severe hemolytic anemia is a common finding. Additionally, many individuals with TPI Df develop neuromuscular symptoms, which is unusual for a glycolytic enzymopathy. There appears to be a genotype-phenotype correlation between a <em>TPI1</em> p.Glu105Asp/null genotype and a severe life-limiting neuromuscular phenotype. <em>Tpi1</em>-deficient mice with a p.Glu105Asp/null genotype recapitulate the life-limiting neuromuscular phenotype seen in humans, but the exact pathomechanism remains unclear. Here we describe a 2-month-old male proband who presented with failure to thrive, respiratory failure, seizures, and severe hemolytic anemia, who passed away at 3 months of age. Trio whole genome sequencing showed compound heterozygous variants with the common p.Glu105Asp variant <em>in trans</em> to a newly described likely pathogenic splice site c.324 + 1G &gt; C variant, predicted to cause nonsense mediated decay. Here we review our case as well as the literature to hypothesize a mechanism by which TPI Df due to a p.Glu105Asp/null genotype causes severe disease. Given the overall fatal nature of this condition, novel therapeutic approaches are urgently needed. Currently, treatments are experimental. Ketogenic diet and triheptanoin were effective in treating seizures in a TPI mutant <em>Drosophila,</em> known as <em>TPI</em>^{<em>sugarkill</em>}<em>,</em> although clinical data in humans is lacking. Additionally, bone marrow transplant has been shown to improve the hematologic phenotype in mice and has been done in an isolated number of patients. While there are no proven therapies available at this time, we hope this review will lead the discussion to consider future therapeutic options.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"146 1","pages":"Article 109227"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923004","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":"Cover 2 / Ed. Board","authors":"","doi":"10.1016/S1096-7192(25)00232-X","DOIUrl":"10.1016/S1096-7192(25)00232-X","url":null,"abstract":"","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"146 1","pages":"Article 109241"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219121","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":"Deep phenotyping of patients with citrin deficiency in Singapore- single centre experience.","authors":"Mildrid Yeo, Jeannette Lay Kuan Goh, Ai Ling Koh, Nikki Fong, Ee Shien Tan, Saumya Jamuar, Chew Yin Jasmine Goh, Eunice Lim, Sherry Poh, Soon Chuan James Lim, Sylvia Kam, Breana Cham, Jiin Ying Lim, Kong Boo Phua, Fang Kuan Chiou, Veena Logarajah, Christopher Wen Wei Ho, Lay Queen Ng, Sarah Ailyne Wong, Lynette Goh, Christine Ong, Grace Quek, Chengsi Ong, Kar Yin Phuah, Teck Wah Ting","doi":"10.1016/j.ymgme.2025.109215","DOIUrl":"10.1016/j.ymgme.2025.109215","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Citrin deficiency (CD) is a pan-ethnic autosomal recessive inborn error of metabolism due to-pathogenic variants in the SLC25A13 gene which results in disruptions of multiple metabolic pathways including glycolysis, gluconeogenesis, lipogenesis, the urea cycle, and tricarboxylic cycle.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A retrospective observational study of CD patients managed according to standard clinical practice at a single centre in Singapore (KK Women's and Children's Hospital, KKH) was undertaken from August 2016-August 2024. We present the largest cohort of patients reported in Southeast Asia focusing on clinical, biochemical and imaging findings at diagnosis, and long-term outcomes/management (including drug therapy, food preferences/adherence, hospital admissions, growth, neurodevelopmental, biochemical, and imaging outcomes). We also explore the utility of newborn screening (NBS) as a means for early detection of CD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Eighteen CD patients (9 males; 2 sibling pairs) majority of Chinese ethnicity (n = 16) with a median duration of follow up 5 years 5 months, participated in this study. Median age at first presentation and at diagnosis was 50 days and 82 days, respectively. Fourteen patients presented with neonatal intrahepatic cholestasis caused by CD (NICCD), 2 asymptomatic from sibling screens, and two from abnormalities on NBS (one presenting with unconjugated hyperbilirubinaemia and the other with cholestasis and liver failure). Two patients had liver failure (one from NICCD group and another from NBS group). None required liver transplantation. All symptomatic patients had raised citrulline and threonine-serine ratios at presentation. None of the patients was prescribed any regular concomitant medications except for MCT oil. No genotype phenotype correlation was observed. At final assessment, all patients showed normalisation of liver parameter, galactose and plasma amino acids. Abnormalities in lipid profile in 9 patients (age 5-16 years) showed borderline high total cholesterol (median 5.4 mmol/L) and LDL (median 3.0 mmol/L) which was on the higher end of the normal range. Sixty-six percent of patients liver imaging findings were normal or showed stable changes. Food preferences (assessed in ≥1-year olds) did not reflect a clear bias towards high protein/fat diet. Adherence appeared to improve with a more prescriptive approach, it waned with age (more so in dietary aspects versus the use of MCT oil). Hospital admissions were few (median 1/patient) and unrelated to CD. Overall improvements were seen in weight, height and BMI for age z-scores, showing median weight/height/BMI for age z-scores to be -0.72, -0.83, 0.08, respectively. None had neurodevelopmental concerns.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;CD remains challenging to diagnose biochemically at all ages. Current NBS strategies require further refining to increase pick up rates of CD. Cascade screening utilising g","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"146 1-2","pages":"109215"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804453","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":"Rapidly progressive, infantile lysosomal acid lipase deficiency: Prevalence in the Mizrahi Jewish population","authors":"Donna L. Bernstein ,&nbsp;Inga Peter ,&nbsp;Robert J. Desnick","doi":"10.1016/j.ymgme.2025.109233","DOIUrl":"10.1016/j.ymgme.2025.109233","url":null,"abstract":"<div><h3>Purpose</h3><div>This study was designed to more accurately estimate the prevalence of severe, infantile onset, rapidly progressive lysosomal acid lipase deficiency (LALD), an autosomal recessive disorder caused by the homoallelic <em>LIPA</em> gene variant, c.260G&gt;T; p.G87V in patients of Mizrahi Jewish ancestry. The previous estimates of LALD prevalence in Middle Eastern and Mizrahi Jewish populations, ranging from 1 in 12,100 to 1 in 4200, were based on historic, observational case reports and a population genetic screening of 165 Middle Eastern individuals and 162 Mizrahi Jews living in Southern California.</div></div><div><h3>Methods</h3><div>Carrier screening of 549 Mizrahi Jewish individuals for the c.260G&gt;T; p.G87V <em>LIPA</em> variant and the common, c.894G&gt;A; p.E8SJM^-1 <em>LIPA</em> variant, was carried out to determine their allele frequencies and expected prevalence of LALD in a larger Mizrahi population.</div></div><div><h3>Results</h3><div>This larger population screening study revealed a <em>LIPA</em> p.G87V Mizrahi founder variant allele frequency of 1 in 52.2, conferring a carrier frequency of 1 in 26.1. Therefore, the occurrence of infantile LALD was estimated to be one in 2724.8 Mizrahi Jewish conceptions in Southern California.</div></div><div><h3>Conclusion</h3><div>The present, larger study found the prevalence of rapidly progressive, infantile LALD disease was ∼35 % greater than the previous prevalence estimate in the major U.S. Mizrahi Jewish population.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"146 1","pages":"Article 109233"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154687","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 'Phosphodiesterase type 5 inhibition as a therapeutic strategy in primary mitochondrial disease: Evidence from patient fibroblasts and clinical observations' [Molecular Genetics and Metabolism Volume 146, Issues 1-2 (2025) Pages 109197].","authors":"G Preston, N Jacob, I Elsharkawi, E Morava, T Kozicz","doi":"10.1016/j.ymgme.2025.109219","DOIUrl":"10.1016/j.ymgme.2025.109219","url":null,"abstract":"","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"146 1-2","pages":"109219"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817180","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":"Progressive activation of the astrocyte A1 phenotype underlies microglia-astroglia crosstalk and contributes to neuroinflammation in neuronopathic MPS","authors":"Andrea Parente ,&nbsp;Luigi Borzacchiello ,&nbsp;Marianna Giaccio ,&nbsp;Martina Bamundo ,&nbsp;Riccardo Rubino ,&nbsp;Ludovica D'Auria ,&nbsp;Antonio Monaco ,&nbsp;Alessandro Fraldi","doi":"10.1016/j.ymgme.2025.109224","DOIUrl":"10.1016/j.ymgme.2025.109224","url":null,"abstract":"<div><div>Neuroinflammation underlies neurodegenerative processes in neuronopathic mucopolysaccharidoses (MPS), with innate immunity known to have a dominating role. Here, by studying mouse models of neuronopathic MPS, we found that the neurotoxic reactive astrocytes A1 are present in the brain of MPS mice and progressively increase with age. Such A1 phenotype is associated to activated microglia and to microglia-mediated release of a subset of specific cytokines involved in the A1 phenotype. Additionally, in the mouse model of MPS-IIIA, one of the most severe neuronopathic MPS in humans, we also found that neuroinflammation proceeded concomitantly with the activation of transglutaminase 2, a multifunctional enzyme involved in a variety of cellular processes, mostly in the microglia. Moreover, amyloid deposition appears to be associated to the maintenance of these processes, indeed, inhibiting amyloid deposition in MPS-IIIA mice reduced TG2 expression, microglia activation and the relative amount of astrocyte A1 phenotype. Our results shed light on the microglia-astroglia crosstalk in neuronopathic MPS and on its implication in neuroinflammation and neurodegeneration in MPS, thus also suggesting new therapeutic targets for these diseases.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"146 1","pages":"Article 109224"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888931","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":"Urine organic acid analysis as a tool in evaluation for Zellweger Spectrum disorder: A retrospective study","authors":"Lekha Chilakamarri ,&nbsp;Matthew B. Neu ,&nbsp;Rebekah Barrick ,&nbsp;Suzette M. Huguenin ,&nbsp;Jose E. Abdenur ,&nbsp;Tina M. Cowan ,&nbsp;Kristina P. Cusmano-Ozog ,&nbsp;Christina G. Tise","doi":"10.1016/j.ymgme.2025.109225","DOIUrl":"10.1016/j.ymgme.2025.109225","url":null,"abstract":"<div><div>This study evaluated the role of urine organic acid (UOA) analysis in eight infants initially flagged by California newborn screening and later diagnosed with Zellweger spectrum disorder (ZSD). Retrospective evaluation of UOA during workup of all patients with ZSD identified a consistent pattern of 2-hydroxysebacic acid, 3,6-epoxydeodecanedioic and 3,6-epoxytetracanedioic acids. These results highlight the value of UOA analysis in the evaluation of ZSD and provide images of clinically relevant peaks on UOA chromatograms.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"146 1","pages":"Article 109225"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908479","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":"The status of adult patients with citrin deficiency in Japan: A report from the nation-wide study","authors":"Jun Kido ,&nbsp;Johannes Häberle ,&nbsp;Keishin Sugawara ,&nbsp;Masahide Yazaki ,&nbsp;Ayano Inui ,&nbsp;Chikahiko Numakura ,&nbsp;Masaru Shimura ,&nbsp;Keinosuke Ishido ,&nbsp;Naomi Kuranobu ,&nbsp;Kenyu Hashimoto ,&nbsp;Kimitoshi Nakamura","doi":"10.1016/j.ymgme.2025.109221","DOIUrl":"10.1016/j.ymgme.2025.109221","url":null,"abstract":"<div><div>Citrin deficiency is an autosomal recessive disorder caused by mutations in <em>SLC25A13</em>, encoding the inner mitochondrial membrane protein citrin. This disease manifests in age-dependent forms: neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), failure to thrive and dyslipidemia caused by citrin deficiency, and adolescent and adult citrin deficiency (AACD). While NICCD often resolves with early treatment, AACD symptoms tend to persist or worsen over time. However, the long-term outcome in adult patients with citrin deficiency, particularly those affected by the symptoms of AACD, is not well understood. To address this gap, we conducted a new study from 2022 to 2024 that focused specifically on adult patients with citrin deficiency.</div><div>This retrospective study investigated the long-term outcomes in a total of 128 adult patients, categorized depending on their onset of disease into NICCD, Post-NICCD, and AACD groups. Significant differences in height were observed: NICCD patients had taller median heights than AACD patients (Males: 170.6 cm vs. 168.0 cm, <em>P</em> = 0.016; Females: 156.0 cm vs. 153.0 cm, <em>P</em> = 0.007). Former NICCD patients generally achieved favorable long-term outcomes with early intervention, while AACD patients often experienced persistent or worsening symptoms, including irreversible liver damage with impaired urea cycle function.</div><div>In conclusion, this study suggests that early intervention during infancy or childhood may improve long-term prognosis in citrin deficiency, particularly for NICCD patients. Conversely, outcome for AACD patients remains a concern, highlighting the need for improved management strategies in adulthood. This study emphasizes the importance of timely diagnosis and treatment to mitigate the progressive nature of citrin deficiency.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"146 1","pages":"Article 109221"},"PeriodicalIF":3.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867074","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}