Molecular genetics and metabolism最新文献

{"title":"The mitochondrial disease biomarker GDF15 is dynamic, quantifiable in saliva, and correlates with disease severity","authors":"Qiuhan Huang ,&nbsp;Caroline Trumpff ,&nbsp;Anna S. Monzel ,&nbsp;Shannon Rausser ,&nbsp;Jack Devine ,&nbsp;Cynthia C. Liu ,&nbsp;Catherine Kelly ,&nbsp;Mangesh Kurade ,&nbsp;Shufang Li ,&nbsp;Kris Engelstad ,&nbsp;Kurenai Tanji ,&nbsp;Vincenzo Lauriola ,&nbsp;Tian Wang ,&nbsp;Shuang Wang ,&nbsp;Richard Sloan ,&nbsp;Robert-Paul Juster ,&nbsp;Michio Hirano ,&nbsp;Martin Picard","doi":"10.1016/j.ymgme.2025.109179","DOIUrl":"10.1016/j.ymgme.2025.109179","url":null,"abstract":"<div><div>Circulating growth differentiation factor 15 (GDF15) is a biomarker of mitochondrial diseases and aging, but its natural dynamics and response to acute stress in blood and other biofluids have not been well defined. Using extensive samples from MiSBIE participants with rare mitochondrial diseases (MitoD), we examined GDF15 biology in 290 plasma and 860 saliva aliquots from 40 subjects with the m.3243 A &gt; G mutation (<em>n</em> = 25) or with single, large-scale mtDNA deletions (<em>n</em> = 15). Compared to healthy controls, both MitoD groups exhibited significantly elevated blood and saliva GDF15 (<em>p</em> &lt; 0.0001). To examine the origin of GDF15 protein in saliva, we profiled <em>GDF15</em> expression in 48 tissues from the GTEx dataset and identified high GDF15 expression in salivary gland secretory cells. Despite being chronically elevated in MitoD, saliva GDF15 further increased in response to experimental laboratory mental stress alone (without physical exertion), whereas the stress-induced plasma GDF15 reactivity was blunted in MitoD compared to controls. Using a home-based saliva collection protocol, we show that similar to other stress-related metabolic hormones, saliva GDF15 is highest upon awakening and declines rapidly by 61.2 % within 45 min. Elevated saliva GDF15 levels persisted throughout the day in MitoD. Clinically, saliva GDF15 correlated with neurological symptoms, fatigue, and functional capacity. Importantly, stress-evoked changes in GDF15 did not amplify noisy disease severity associations, but rather consistently increased the effects sizes for GDF15-symptoms connections, pointing to converging psychobiology underlying the responses to mitochondrial OxPhos defects and acute mental stress. These results open the door to exploring saliva GDF15 as a non-invasive monitoring approach for mitochondrial diseases and call for further studies examining the psychobiological processes linking mitochondria, mental stress, and GDF15 dynamics.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 4","pages":"Article 109179"},"PeriodicalIF":3.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518738","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":"Antioxidant therapy in inborn metabolic diseases","authors":"Felix Heimes ,&nbsp;Lea-Sophie Berendes ,&nbsp;Luciana Hannibal ,&nbsp;Julien Park","doi":"10.1016/j.ymgme.2025.109176","DOIUrl":"10.1016/j.ymgme.2025.109176","url":null,"abstract":"<div><div>Oxidative stress contributes to the pathophysiology of several inherited metabolic diseases (IMDs). The quality and extent of clinical evidence for the use of antioxidant therapies in IMDs have yet to be ascertained. Despite frequent clinical use, robust evidence from large-scale trials is limited. The strongest support comes from studies on idebenone in Leber's hereditary optic neuropathy, showing improvements in visual outcomes. For other antioxidants and conditions, evidence is mixed or constrained by small sample sizes and short trial durations. Coenzyme Q10 in mitochondrial diseases, vitamin E in lipid disorders, and <em>N</em>-acetylcysteine in various IMDs have shown some promise, but evidence is heterogeneous. Challenges include optimizing dosing, dissecting oxidative stress mechanisms across disorders, and overcoming pharmacokinetic limitations. High-grade evidence exists for the clinical efficacy of <em>N</em>-acetyl-L-leucine for both Niemann Pick type C disease and other lysosomal storage diseases, though its potential antioxidant effect is indirect. This review highlights the need for larger trials with standardized, clinically relevant outcomes. Future research should explore oxidative stress mechanisms, targeted therapies, and combination approaches. While antioxidants hold potential, evidence remains limited, warranting cautious use and further investigation to define their role in these rare but cumulatively impactful disorders.</div></div><div><h3>Synopsis</h3><div>This review finds limited robust evidence for antioxidant therapies in inherited metabolic diseases, highlighting the need for larger trials and more targeted approaches.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 4","pages":"Article 109176"},"PeriodicalIF":3.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314503","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":"Multiorgan involvement and genetic spectrum of 20 Chinese patients with PMM2-CDG","authors":"Huiting Zhang ,&nbsp;Jingtao Zhang ,&nbsp;Weimeng Ma ,&nbsp;Xue Ma ,&nbsp;Ruxuan He ,&nbsp;Yuan Ding ,&nbsp;Yupeng Liu ,&nbsp;Wenyue Zhang ,&nbsp;Hui Dong ,&nbsp;Yao Zhang ,&nbsp;Miao He ,&nbsp;Yanling Yang","doi":"10.1016/j.ymgme.2025.109178","DOIUrl":"10.1016/j.ymgme.2025.109178","url":null,"abstract":"<div><h3>Objective</h3><div>The most common congenital disorders of glycosylation (CDG) is the phosphomannomutase 2 (PMM2) deficiency (PMM2-CDG). PMM2-CDG is a complex genetic disorder that often found in infancy or early childhood with a clinically heterogeneous variety of neurological and non- neurological symptoms. To expand the phenotypic and genetic spectrum of PMM2-CDG, we summarized the characteristics of 20 Chinese patients.</div></div><div><h3>Methods</h3><div>All patients were diagnosed by genetic analysis. Clinical characteristics, genotypes, imaging, electrophysiological, and metabolic data were analyzed retrospectively.</div></div><div><h3>Results</h3><div>Twelve males and eight females with PMM2-CDG were included. The median age at diagnosis was 12.0 (ranging from 6.0 to 52.0) months, while the median age at final follow-up was 10.3 (ranging from 5.1 to 12.8) years. All patients exhibited multisystem symptoms and various neurological symptoms were observed. Developmental delay was the primary initial symptoms. Dystaxia, growth retardation and liver damage were also common phenotypes. Cerebellar atrophy was the characteristic abnormality on brain imaging. Fourteen variants of the PMM2 gene were identified, of which five, c.82A &gt; G (p.M28V), c.551C &gt; T (p. P184L), c.640G &gt; T (p.G214C), c.656A &gt; T (p.E219V) and c.712C &gt; G (p.R238G), were newly reported. The most prevalent variant was c.430 T &gt; C (p.F144L), which was identified in 65.0 % of patients, followed by c.395 T &gt; C (p.I132T). Consistent with reports from other populations, missense variants constituted the predominant type of PMM2 gene alterations.</div></div><div><h3>Conclusion</h3><div>PMM2-CDG presents as a multi-system disease with diverse clinical phenotypes, posing challenges to early identification and diagnosis. The most common pathogenic variant in this Chinese cohort was c.430 T &gt; C (p.F144L), which is close to, but different from, the common pathogenic variant c.422G &gt; A (p.R141H) among European PMM2-CDG patients.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 4","pages":"Article 109178"},"PeriodicalIF":3.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365758","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 origin of abnormal organic acids in HMG-CoA synthase deficiency","authors":"F.-G. Debray ,&nbsp;E. Van Schaftingen","doi":"10.1016/j.ymgme.2025.109177","DOIUrl":"10.1016/j.ymgme.2025.109177","url":null,"abstract":"","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 4","pages":"Article 109177"},"PeriodicalIF":3.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306275","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":"Prevalence of fibrosis in hepatic explants and biopsies from individuals with urea cycle disorders","authors":"Saima Ali ,&nbsp;Aisha Nisar ,&nbsp;Anqing Zhang ,&nbsp;Sandesh Nagamani ,&nbsp;Nathalie M. Aceves-Ewing ,&nbsp;Brandy Rawls ,&nbsp;Thu Quan ,&nbsp;Greg Enns ,&nbsp;John Goss ,&nbsp;Daniel H. Leung ,&nbsp;Benjamin L. Shneider ,&nbsp;Shilpa Jain ,&nbsp;Florette K. Hazard ,&nbsp;Deborah Schady ,&nbsp;Lindsay C. Burrage","doi":"10.1016/j.ymgme.2025.109175","DOIUrl":"10.1016/j.ymgme.2025.109175","url":null,"abstract":"<div><h3>Background</h3><div>Various forms of liver disease have been increasingly reported in individuals with urea cycle disorders (UCDs). In this study, we performed the first systematic and standardized histopathological assessment of the prevalence of fibrosis and steatosis in a large sample of hepatic explants and biopsies from individuals with UCDs at two liver transplantation centers.</div></div><div><h3>Methods</h3><div>Sixty-seven hepatic tissue samples from 66 individuals with UCDs were staged by two pathologists for hepatic fibrosis and steatosis using standard scoring systems at two large liver transplantation centers in the United States. Histopathological findings were correlated with clinical parameters, including UCD type, laboratory parameters, and imaging findings.</div></div><div><h3>Results</h3><div>Overall, 23 % (<em>n</em> = 15) of individuals demonstrated clinically significant hepatic fibrosis (≥ F2 according to Metavir staging). Of these, 12 were diagnosed with argininosuccinate lyase deficiency (ASLD) leading to an 80 % prevalence of clinically significant fibrosis in this disorder in this cohort. Eighteen percent of the patients (<em>n</em> = 12) had microvesicular and/or macrovesicular hepatic steatosis. No clinical parameters including routine laboratory testing or imaging were significantly associated with clinically significant hepatic fibrosis in individuals with ASLD.</div></div><div><h3>Conclusion</h3><div>In this large study of hepatic histopathology in UCDs, our findings demonstrate a high prevalence of clinically significant hepatic fibrosis in ASLD. These findings emphasize the importance of monitoring for liver disease and promoting liver health in UCDs and may have implications for long-term monitoring for individuals with ASLD.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 4","pages":"Article 109175"},"PeriodicalIF":3.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314502","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":"Colonic xanthomas in an adult with skeletal anomalies and dyslipidemia: Colonoscopic findings of NSDHL-related CHILD syndrome due to NSDHL haploinsufficiency","authors":"Bukola A. Olarewaju ,&nbsp;Judy B. Tejon ,&nbsp;Misha B. Asif ,&nbsp;Mayowa A. Osundiji","doi":"10.1016/j.ymgme.2025.109174","DOIUrl":"10.1016/j.ymgme.2025.109174","url":null,"abstract":"","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 4","pages":"Article 109174"},"PeriodicalIF":3.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288700","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":"Clinical and genetic features of Classic Galactosemia in the south of Brazil","authors":"Leonardo Simão Medeiros ,&nbsp;Lucas Ferreira Teixeira ,&nbsp;Alexandra Gomes ,&nbsp;Isabel Rivera ,&nbsp;Cláudia Fernandes Lorea ,&nbsp;Lilia Farret ,&nbsp;Kristiane Michelin Tirelli ,&nbsp;Fernanda Medeiros Sebastião ,&nbsp;Fernanda Bender Pasetto ,&nbsp;Carolina Fischinger Moura de Souza ,&nbsp;Fabiano de Oliveira Poswar ,&nbsp;Raquel Borges Pinto ,&nbsp;Mariana Marcano-Ruiz ,&nbsp;Fernanda Sperb-Ludwig ,&nbsp;Sandra Maria Vieira ,&nbsp;Lavínia Schuler-Faccini ,&nbsp;Ida Vanessa Doederlein Schwartz","doi":"10.1016/j.ymgme.2025.109173","DOIUrl":"10.1016/j.ymgme.2025.109173","url":null,"abstract":"<div><h3>Introduction</h3><div>Classic Galactosemia (CG) is a rare metabolic disorder that leads to acute neonatal hepatic dysfunction, with striking improvement after diet treatment. However, long-term complications, such as intellectual deficits, often persist.</div></div><div><h3>Aim</h3><div>To describe the demographic, clinical, and genetic features of CG in a cohort of patients from South Brazil.</div></div><div><h3>Methods</h3><div>Data were retrieved through medical charts review of CG patients followed in Rio Grande do Sul, Brazil.</div></div><div><h3>Results</h3><div>Thirty-one patients were included (families = 29; ethnicity: white = 20, indigenous Kaingang = 9, black = 2; female = 14). Five patients were diagnosed through private NBS and began treatment at a median age of 17 days (15–30), while others presented symptoms at 5 days (1–19) starting treatment at 27 days (5–4680). Eight patients presented Cerebral Palsy, Microcephaly, and/or Epilepsy, and two had died. Notable clinical findings were the “double cap sign” in Brain MRI (<em>n</em> = 1), pseudohyperglycemia (<em>n</em> = 3), and elevated chitotriosidase activity (n = 3). <em>GALT</em> sequencing was performed in 25/31 patients, and the most frequent causal variant found was c.563 A &gt; G (p.Gln188Arg). Two novel variants were detected: c.164G &gt; T (p.Gly55Val), associated with clinical variant galactosemia; and a novel haplotype c.[90dup; 529 A &gt; G] (p.[His31Alafs*9;Met177Val]) detected in Kaingang patients. The minimal prevalence of CG in this Indigenous population was estimated in at least 1:900 live births.</div></div><div><h3>Conclusion</h3><div>This data improves the characterization of CG in symptomatic diagnosed patients and identifies a high incidence of CG in the Kaingang people due to a founder effect.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 4","pages":"Article 109173"},"PeriodicalIF":3.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271537","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":"Use of lysine reduction therapies in patients with pyridoxine dependent epilepsy due to Antiquitin deficiency – A cohort study","authors":"Emma J. Footitt ,&nbsp;Chloe Millington ,&nbsp;Imogen Newsom-Davis ,&nbsp;Philippa Mills ,&nbsp;Youssef Khalil ,&nbsp;Peter T. Clayton ,&nbsp;Marjorie Dixon","doi":"10.1016/j.ymgme.2025.109170","DOIUrl":"10.1016/j.ymgme.2025.109170","url":null,"abstract":"<div><div>Pyridoxine dependent epilepsy due to Antiquitin deficiency (PDE-ALDH7A1) is a disorder of lysine catabolism that results in accumulation of α- aminoadipic semialdehyde (α-AASA) and Δ1-piperideine 6-carboxylic acid (P6C). It is hypothesised that these metabolites are neurotoxic and that chronic exposure may have detrimental long-term effects, particularly on the young developing brain.</div><div>Lysine reduction therapies in the form of lysine restricted diet (LRD) and arginine, have been used as an adjunct to pyridoxine for the treatment of PDE-ALDH7A1 for the last 15 years with an aim to improve long-term developmental outcomes by reducing α-AASA and P6C. We present the management and outcomes for a cohort of 17 PDE-ALDH7A1 patients from our centre.</div><div>In this study we show that LRD leads to a reduction in plasma lysine levels and urine α-AASA concentrations and a correlation between these is seen in individual patients, supporting the treatment hypothesis.</div><div>LRD alone was shown to be sufficient to reduce plasma lysine into the target treatment range and addition of arginine was not required.</div><div>Transition to LRD and long-term adherence is easier to achieve in patients under 6 months of age, compared to older patients.</div><div>Lysine reduction therapies did not offer any additional benefit on seizure control over pyridoxine monotherapy but in keeping with previous studies, this study supports early initiation of LRD in patients under 6 months with cognitive function scores maintained in some, although longer term follow up is required and ongoing.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 4","pages":"Article 109170"},"PeriodicalIF":3.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655950","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":"Differentiation of neonatal and infantile onset ECHS1 deficiency using SCEH enzyme activity and plasma acylcarnitine analysis","authors":"Olivia D'Annibale ,&nbsp;Whitney Phinney ,&nbsp;Molly Crenshaw ,&nbsp;Mary Kate LoPiccolo ,&nbsp;Ibrahim Elsharkawi ,&nbsp;Emily Shelkowitz ,&nbsp;Daniel Pique ,&nbsp;Rodrigo T. Starosta ,&nbsp;Austin Larson ,&nbsp;Johan L.K. Van Hove ,&nbsp;Tim Wood ,&nbsp;Aaina Kochhar","doi":"10.1016/j.ymgme.2025.109156","DOIUrl":"10.1016/j.ymgme.2025.109156","url":null,"abstract":"<div><div>Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) is an autosomal recessive disorder that presents in the neonatal or infantile period with encephalopathy and lactic acidosis. Biomarkers are variable, with many ECHS1D patients having elevated plasma C4-carnitine and urine 2-methyl-2,3-dihydroxybutyric acid while others have none. Neonates often succumb prior to molecular sequencing results being returned. ECHS1D diagnosis may be faster if biomarkers are used in plasma and urine along with enzyme activity measurement. Short-chain enoyl-CoA hydratase activity was performed in six ECHS1D fibroblasts with neonatal or infantile onset. DBS cards were obtained from two patients and one carrier. Control fibroblasts (<em>n</em> = 11) activity was 229.62 ± 68.52 nmol/min/mg. Neonatal ECHS1D fibroblasts activity was 3.92 ± 0.62 nmol/min/mg. Infantile onset ECHS1D fibroblasts activity was 17.27 ± 2.14 nmol/min/mg. Control DBS SCEH activity was 141.18 ± 34.00 nmol/min/mg (<em>n</em> = 10) and one neonatal and infantile patient sample showed approximately 2 % and 27 % activity, respectively. One carrier had 45 % activity. We described five new cases of ECHS1D and analyzed seven total cases. We determined SCEH activity reference ranges in neonatal and infantile onset ECHS1D fibroblasts. For the first time, we demonstrated SCEH activity in DBS with separation between ECHS1D and controls. SCEH activity in DBS could allow for newborn screening for ECHS1D as new treatments are developed.</div></div><div><h3>Synopsis</h3><div>Neonatal and infantile onset ECHS1D can be differentiated via fibroblast and dried blood spot short-chain enoyl-CoA hydratase activity and detection of plasma S-(2-carboxypropyl)cysteine carnitine species to allow for faster diagnosis and prompt treatment.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 4","pages":"Article 109156"},"PeriodicalIF":3.7,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279157","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":"Treatment preferences of adult patients with hereditary fructose intolerance: A discrete choice experiment","authors":"Lise E.F. Janssen ,&nbsp;Mickaël Hiligsmann ,&nbsp;Corrie Timmer ,&nbsp;Liesbeth M.C. van der Ploeg ,&nbsp;Kristel Vande Kerckhove ,&nbsp;Timothy Cox ,&nbsp;Javier de las Heras ,&nbsp;David Cassiman ,&nbsp;Martijn C.G.J. Brouwers","doi":"10.1016/j.ymgme.2025.109169","DOIUrl":"10.1016/j.ymgme.2025.109169","url":null,"abstract":"<div><h3>Background</h3><div>Patients with hereditary fructose intolerance (HFI) follow a fructose-restricted diet to avoid life-threatening complications. The aim of this study was to investigate whether patients with HFI have a preference for a pharmacological therapy as an add-on or replacement of their current diet.</div></div><div><h3>Methods</h3><div>Adult patients with HFI recruited from metabolic clinics and through social media (<em>n</em> = 90) were asked to complete a labelled discrete choice experiment (DCE). The DCE was composed after personal interviews with patients (<em>n</em> = 3) and health care providers (<em>n</em> = 6), and contained 12 choice sets. In each choice set, patients were asked to choose between their current fructose-restricted diet or pharmacological therapy, which consisted of four attributes: side effects, costs, mode of administration and effect on fructose restriction.</div></div><div><h3>Results</h3><div>Although the random parameter model showed that patients on average preferred their current diet over a putative pharmacological therapy, 86 % of the patients opted for pharmacological therapy in at least one of the choice tasks. One tablet daily on special occasions without any fructose restriction, no side effects and no additional costs were significantly associated with a preference for pharmacological therapy. Younger age, more daily impact of the disease and more daily impact of the dietary restriction were associated with a preference for pharmacological therapy.</div></div><div><h3>Conclusions</h3><div>Under specific conditions, patients with HFI prefer a pharmacological therapy over their fructose-restricted diet. Therapy-related factors as well as patient-related factors play a role in this choice. These findings may guide the development and implementation of a pharmacologic therapy for patients with HFI.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"145 4","pages":"Article 109169"},"PeriodicalIF":3.7,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254874","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}