Journal of Inherited Metabolic Disease最新文献

{"title":"Phosphoribosylformylglycinamidine Synthase (PFAS) Deficiency: Clinical, Genetic and Metabolic Characterisation of a Novel Defect in Purine de Novo Synthesis","authors":"Marie Zikanova,&nbsp;Vaclava Skopova,&nbsp;Kyra E. Stuurman,&nbsp;Veronika Baresova,&nbsp;Olga Souckova,&nbsp;Ales Hnizda,&nbsp;Matyas Krijt,&nbsp;Anthony J. Bleyer,&nbsp;Jiri Zeman,&nbsp;Stanislav Kmoch","doi":"10.1002/jimd.70041","DOIUrl":"https://doi.org/10.1002/jimd.70041","url":null,"abstract":"<p>Purine de novo purine synthesis involves 10 reactions catalysed by six enzymes, including phosphoribosylformyglycinamidine synthase (PFAS). To date, genetic defects of three of these enzymes, namely ATIC, ADSL and PAICS, have been characterised in humans. Here, we report for the first time two individuals with PFAS deficiency. Probands were identified through metabolic and genetic screening of neurologically impaired individuals. The pathogenicity of the variants was established by structural and functional studies. Probands C1 and C2 presented with prematurity, short stature, recurrent seizures and mild neurological impairment. C1 had elevated urinary levels of formylglycineamide riboside (FGAr) and bi-allelic PFAS variants encoding the NP_036525.1:p.Arg811Trp substitution and the NP_036525.1:p.Glu228_Ser230 in-frame deletion. C2 is a 20-year-old female with a homozygous NP_036525.1:p.Asn264Lys substitution. These amino acid changes are predicted to affect the structural stability of PFAS. Accordingly, C1 skin fibroblasts showed decreased PFAS content and activity, with impaired purinosome formation that was restored by transfection with pTagBFP_PFAS_wt. The enzymatic activities of the corresponding recombinant mutant PFAS proteins were also reduced, and none of them, after transfection, corrected the elevated FGAR/r levels in PFAS-deficient HeLa cells. While genetic defects in purine de novo synthesis are typically considered in patients with severe neurological impairment, these disorders, especially PFAS deficiency, should also be considered in milder phenotypes.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Treatment Strategy for Patients With Urea Cycle Disorders: Pharmacological Chaperones Enhance Enzyme Stability and Activity in Patient-Derived Liver Disease Models","authors":"Adhuresa Ramosaj,&nbsp;Mariia Borsuk,&nbsp;Jarl Underhaug,&nbsp;Déborah Mathis,&nbsp;Shirou Matsumoto,&nbsp;Adrian Keogh,&nbsp;Vanessa Banz,&nbsp;Amit V. Pandey,&nbsp;Nadine Gougeard,&nbsp;Vicente Rubio,&nbsp;Aurora Martinez,&nbsp;Gabriella Allegri,&nbsp;Martin Poms,&nbsp;Beat Thöny,&nbsp;Johannes Häberle,&nbsp;Alexander Laemmle","doi":"10.1002/jimd.70043","DOIUrl":"https://doi.org/10.1002/jimd.70043","url":null,"abstract":"<p>Urea cycle disorders (UCDs) are inherited diseases causing recurrent life-threatening metabolic decompensations due to impaired hepatic ammonia detoxification and decreased ureagenesis. Ornithine transcarbamylase (OTC) deficiency (OTCD) is X-linked and the most common and often fatal UCD. In male hemizygous patients, disease severity primarily depends on the pathogenic sequence variant, while in heterozygous females, disease severity also depends on the X-chromosomal inactivation (XCI) pattern. Females with unfavorable XCI predominantly expressing the mutant OTC protein may be severely affected. Here, we investigated a novel treatment strategy for OTCD since there is an unmet need for better therapies. In the first step, we performed a high throughput screening (HTS) using a diversity library with 10 000 chemical compounds to identify pharmacological chaperone (PC) candidates that stabilize purified wild-type OTC. Stratification of our HTS results revealed five potential PCs, which were selected for further experimentation in cellular systems using primary human hepatocytes (PHHs) and human induced pluripotent stem cell (hiPSC)-derived hepatocytes (hiPSC-Heps) from healthy controls and OTCD patients. Two PCs—PC1 and PC4—increased OTC protein stability and activity in control hiPSC-Heps, while PC4 in addition increased OTC activity in patient-derived PHHs from a female OTCD patient with unfavorable XCI. Finally, PC1 and PC4 both significantly increased ureagenesis in patient-derived PHHs. To conclude, we identified two PCs that stabilized wild-type OTC and enhanced enzyme activity and ureagenesis. Our work suggests that PCs could provide a novel treatment strategy for OTCD specifically in females with unfavorable XCI.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis of Inherited Metabolic Disease in Older Patients: A Systematic Literature Review","authors":"Maria-Rita Moio,&nbsp;Julia Cordeiro Milke,&nbsp;Yannick Moutapam-Ngamby-Adriaansen,&nbsp;Arthur Minas Alberti,&nbsp;Marie Gernay,&nbsp;Eduardo Schütz,&nbsp;Ida Vanessa Doederlein Schwartz,&nbsp;François Maillot","doi":"10.1002/jimd.70038","DOIUrl":"https://doi.org/10.1002/jimd.70038","url":null,"abstract":"<p>Inherited metabolic diseases (IMDs) are genetic disorders that disrupt biochemical processes in the human body, due to pathogenic variants in genes encoding enzymes or transporters. While IMDs are mostly diagnosed in infancy or childhood, there is an increasing number of diagnoses in adult patients. Delayed diagnosis, particularly in older patients, may reflect the diagnostic odyssey usually observed in rare diseases' patients and can result in complications and reduced quality of life for patients and their families. The aim of the study was to better characterize the diagnosis of IMDs in older patients (≥ 65 years). We conducted a systematic literature review (SLR) to examine the diagnosis and clinical presentation of IMDs in patients aged 65 and older. We searched databases like PubMed, Embase, and Lilacs for relevant studies from 1965 to 2023. A total of 260 articles were included, representing 293 patients with a median age of 69 years at diagnosis. From this SLR, 67 different diagnoses have been reported. The most frequently reported diseases were Fabry disease, alkaptonuria, Gaucher disease, mitochondrial disorders, and glycogen storage disease type V. Median diagnostic delay was 14.5 years with a wide range of 1–91 years. Musculoskeletal symptoms were the most frequently reported, followed by neurological and cardiovascular symptoms. Our findings underscore the importance of recognizing IMDs in older patients and the need for awareness among healthcare providers to improve diagnosis and patient care. Future guidelines and teaching programs should incorporate metabolic investigations for older patients presenting with symptoms suggestive of IMDs.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glut1 Deficiency Syndrome: Novel Pathomechanisms, Current Concepts, and Challenges","authors":"Joerg Klepper","doi":"10.1002/jimd.70044","DOIUrl":"https://doi.org/10.1002/jimd.70044","url":null,"abstract":"<p>Glut1 Deficiency Syndrome (Glut1DS) has emerged as a treatable, but complex entity. Increasing data on pathogenic mechanisms, phenotype, genotype, and ketogenic dietary therapies (KDT) are available, as summarized in this review. Many challenges remain: novel symptoms emerge and vary with age. In Glut1DS, KDT in pregnancy and the clinical features in neonates and adults are poorly understood. KDT are ineffective in some patients for reasons yet unknown. Research reaches beyond the concept of brain energy depletion by impaired GLUT1-mediated glucose transfer across the blood–brain barrier. Novel concepts investigate alternative substrates, transport mechanisms, and metabolic interactions of different brain cell types. Future, yet currently unavailable prospects are neonatal screening for Glut1DS, reliable biomarkers, predictors for outcome, and alternative therapies, along with and beyond KDT.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenosine Kinase: An Epigenetic Modulator and Drug Target","authors":"Uchenna Peter-Okaka,&nbsp;Detlev Boison","doi":"10.1002/jimd.70033","DOIUrl":"https://doi.org/10.1002/jimd.70033","url":null,"abstract":"<p>Adenosine kinase (ADK, EC: 2.7.1.20) is an evolutionarily ancient ribokinase, which acts as a metabolic regulator by transferring a phosphoryl group to adenosine to form AMP. The enzyme is of interest as a therapeutic target because its inhibition is one of the most effective means to raise the levels of adenosine and hence adenosine receptor activation. For these reasons, ADK has received significant attention in drug discovery efforts in the early 2000s for indications such as epilepsy, chronic pain, and inflammation; however, the report of adverse events regarding cardiovascular and hepatic function as well as instances of microhemorrhage in the brain of preclinical models prevented further development efforts. Recent findings emphasize the importance of compartmentalization of the adenosine system reflected by two distinct isoforms of the enzyme, ADK-S and ADK-L, expressed in the cytoplasm and the cell nucleus, respectively. Newly identified adenosine receptor independent functions of adenosine as a regulator of biochemical transmethylation reactions, which include DNA and histone methylation, identify ADK-L as a distinct therapeutic target for the regulation of the nuclear methylome. This newly recognized role of ADK-L as an epigenetic regulator points toward the potential disease-modifying properties of the next generation of ADK inhibitors. Continued efforts to develop therapeutic strategies to separate nuclear from extracellular functions of adenosine would enable the development of targeted therapeutics with reduced adverse event potential. This review will summarize recent advances in the discovery of novel ADK inhibitors and discuss their potential therapeutic use in conditions ranging from epilepsy to cancer.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin B6 Status in Hypophosphatasia: Association With Clinical Severity, Diagnostic Utility, and Effects on Vitamin B6 Metabolism by Supplementation and Enzyme Replacement Therapy","authors":"Tomoyuki Akiyama,&nbsp;Takuo Kubota,&nbsp;Kei Murayama,&nbsp;Makoto Fujiwara,&nbsp;Yasuhisa Ohata,&nbsp;Keiichi Ozono,&nbsp;Makiko Tajika,&nbsp;Keiko Ichimoto,&nbsp;Yohei Sugiyama,&nbsp;Mari Akiyama,&nbsp;Takashi Shibata,&nbsp;Hiroki Tsuchiya","doi":"10.1002/jimd.70036","DOIUrl":"https://doi.org/10.1002/jimd.70036","url":null,"abstract":"<div>\u0000 \u0000 <p>This study reports the concentrations of major vitamin B6 (VB6) vitamers (pyridoxal 5′-phospate [PLP], pyridoxal [PL], and 4-pyridoxic acid [PA]) in over 100 hypophosphatasia (HPP) cases to explore clues for clinical severity, to improve diagnostic sensitivity, and to examine VB6 changes by supplementation and enzyme replacement therapy. Serum samples were collected from HPP and non-HPP patients. When available, cerebrospinal fluid (CSF) samples were also analyzed to determine PLP, PL, and PA concentrations. Serum PLP concentrations, PLP-to-PL ratios, and PLP-to-PA ratios were higher in untreated HPP patients compared to non-HPP patients and reflected clinical severity. Perinatal severe HPP showed lower PL concentrations than perinatal benign HPP and the lowest PA concentrations among all clinical forms. Combining PLP-to-PL ratios with PLP concentrations improved diagnostic sensitivity. Under VB6 therapy, PLP concentrations and PLP-to-PL ratios remained higher in HPP patients than in non-HPP patients. VB6 changes produced by ERT were most clearly reflected by the reduction of PLP-to-PL ratios. CSF PLP concentrations and PLP-to-PL ratios were higher in untreated HPP patients than in non-HPP patients, while CSF PL concentrations were higher in patients on ERT compared to those not on ERT. Co-evaluation of serum PLP, PL, and PA concentrations may help understand clinical severity, can improve diagnostic sensitivity, and can demonstrate the effect of ERT on VB6 metabolism more effectively than the assay of PLP concentrations alone. Altered VB6 status in the CSF suggests that tissue-nonspecific alkaline phosphatase plays a key role in VB6 transport from peripheral blood to the brain via the blood–CSF barrier.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic Form of Dihydrolipoamide Dehydrogenase Deficiency (DLDD): Phenotypic Spectrum, Laboratory Findings, and Therapeutic Approaches in 52 Patients","authors":"Nicole Hammann,&nbsp;Christian Staufner,&nbsp;Lea Dewi Schlieben,&nbsp;Antal Dezsőfi-Gottl,&nbsp;René G. Feichtinger,&nbsp;Johannes Häberle,&nbsp;Norman Junge,&nbsp;Vassiliki Konstantopoulou,&nbsp;Robert Kopajtich,&nbsp;Valérie McLin,&nbsp;Daisy Rymen,&nbsp;Christoph Slavetinsky,&nbsp;Ekkehard Sturm,&nbsp;Johannes A. Mayr,&nbsp;Matias Wagner,&nbsp;Stefan Kölker,&nbsp;Holger Prokisch,&nbsp;Georg F. Hoffmann,&nbsp;Dominic Lenz","doi":"10.1002/jimd.70035","DOIUrl":"https://doi.org/10.1002/jimd.70035","url":null,"abstract":"<p>Dihydrolipoamide dehydrogenase deficiency (MIM 246900/DLDD) is an autosomal recessive mitochondrial disease with three clinical subgroups. The hepatic form leads to recurrent metabolic decompensations often accompanied by elevated levels of liver transaminases (ELT) in blood, sometimes progressing to acute liver failure (ALF). Genetically, it is linked to the p.G229C variant in the <i>DLD</i> gene, which has been reported in the Ashkenazi Jewish and Arabic population. In this study, we analyzed phenotypic diversity, therapeutic management, and outcome in novel symptomatic individuals with hepatic DLDD identified by whole exome sequencing (<i>n</i> = 7) in Central Europe as well as in previously reported cases (<i>n</i> = 45). Fifty-one of 52 DLDD patients carried the p.G229C variant (39 in a homozygous state). During decompensations, precipitated by febrile infectious disease or fasting, affected individuals presented with nausea, vomiting, abdominal pain, hepatomegaly, hypoglycemia, and lactic acidosis. In individuals homozygous for the p.G229C variant, neurologic manifestations were rare, whereas mild neurologic symptoms were found in individuals (<i>n</i> = 8) carrying a different <i>DLD</i> variant <i>in trans</i>. During decompensation, levels of specific plasma amino acids like citrulline or branched-chain amino acids, and urinary organic acids, like 2-oxoglutaric acid, were frequently elevated. However, known biomarkers—with the exception of lactate—were not consistently elevated during these episodes and typically normal in the interval, highlighting the usefulness of early genetic testing in all children with unexplained ELT or ALF to reduce the time to diagnosis. While there exists consensus for rescue therapy with intravenous glucose during decompensations and maintenance therapy with riboflavin, therapies with thiamine and antioxidants (e.g., N-acetylcysteine) were reported to be useful in single individuals with recurrent decompensations.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep Learning Study of Alkaptonuria Spinal Disease Assesses Global and Regional Severity and Detects Occult Treatment Status","authors":"Kendall A. Flaharty,&nbsp;Vibha Chandrasekar,&nbsp;Irene J. Castillo,&nbsp;Dat Duong,&nbsp;Carlos R. Ferreira,&nbsp;Suzanna Ledgister Hanchard,&nbsp;Ping Hu,&nbsp;Rebekah L. Waikel,&nbsp;Francis Rossignol,&nbsp;Wendy J. Introne,&nbsp;Benjamin D. Solomon","doi":"10.1002/jimd.70042","DOIUrl":"https://doi.org/10.1002/jimd.70042","url":null,"abstract":"<p>Deep learning (DL) is increasingly used to analyze medical imaging, but is less refined for rare conditions, which require novel pre-processing and analytical approaches. To assess DL in the context of rare diseases, this study focused on alkaptonuria (AKU), a rare disorder that affects the spine and involves other sequelae; treatments include the medication nitisinone. Since assessing x-rays to determine disease severity can be a slow, manual process requiring considerable expertise, this study aimed to determine whether these DL methods could accurately identify overall spine severity at specific regions of the spine and whether patients were receiving nitisinone. DL performance was evaluated versus clinical experts using cervical and lumbar spine radiographs. DL models predicted global severity scores (30-point scale) within 1.72 ± 1.96 points of expert clinician scores for cervical and 2.51 ± 1.96 points for lumbar radiographs. For region-specific metrics, the degrees of narrowing, calcium, and vacuum disc phenomena at each intervertebral space (IVS) were assessed. The model's narrowing scores were within 0.191–0.557 points from clinician scores (6-point scale), calcium was predicted with 78%–90% accuracy (present, absent, or disc fusion), and vacuum disc phenomenon predictions were less consistent (41%–90%). Intriguingly, DL models predicted nitisinone treatment status with 68%–77% accuracy, while expert clinicians appeared unable to discern nitisinone status (51% accuracy) (<i>p</i> = 2.0 × 10⁻⁹). This highlights the potential for DL to augment certain types of clinical assessments in rare disease, as well as identifying occult features like treatment status.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"State of the Art and Consensus Statements by Healthcare Providers, Patients, and Caregivers on Continuous Glucose Monitoring in Liver Glycogen Storage Diseases","authors":"Terry G. J. Derks,&nbsp;Ruben J. Overduin,&nbsp;Sarah C. Grünert,&nbsp;Alessandro Rossi,&nbsp;CGM GSD Collaborators Group","doi":"10.1002/jimd.70040","DOIUrl":"https://doi.org/10.1002/jimd.70040","url":null,"abstract":"<p>Continuous glucose monitoring (CGM) is increasingly used although not officially registered for the management of people living with liver glycogen storage diseases (GSDs). The aims of this study were twofold: (a) to investigate the current experiences of healthcare providers (HCPs), patients, and caregivers using CGM to monitor glucose concentrations in liver GSDs, and (b) to formulate consensus statements. Two web-based questionnaires were distributed, one for HCPs and one for patients and/or their caregivers. The questionnaires collected data on demographics and epidemiology, current use of CGM, and opinions and statements about CGM in GSDs. For the statements, respondents rated their agreement on a 5-point Likert scale, and the consensus level was set at 75%. One Hundred Fourteen HCPs (including 87 physicians and 26 dietitians) from 28 countries responded, representing care of approximately 3800 liver GSD patients. Additionally, 148 GSD patients and/or their caregivers from 21 countries responded, mainly representing GSD Ia (<i>n</i> = 50), GSD Ib (<i>n</i> = 56), GSD III (<i>n</i> = 14), and GSD IX (<i>n</i> = 18). The median age to consider starting to use CGM was 6 and 2 months for HCPs and GSD families, respectively. Out of 16 statements common to the two questionnaires, HCPs and patients/caregivers reached consensus on 12 statements in both groups. Use of CGM is considered standard of care by both HCPs and GSD families, but reimbursement of CGM devices is challenging. Compared to diabetes mellitus, CGM should be applied differently in liver GSDs. Consensus guidelines are warranted on the use of CGM in liver GSDs, both in routine healthcare and in clinical trials.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of Gaucher Disease in France: Trends in Incidence, Mortality, Management, and Complications Over Three Decades","authors":"Yann Nguyen,&nbsp;Maxime Beydon,&nbsp;Karima Yousfi,&nbsp;Samira Zebiche,&nbsp;Dalil Hamroun,&nbsp;Anaïs Brassier,&nbsp;Samia Pichard,&nbsp;Laure Swiader,&nbsp;Thierry Billette de Villemeur,&nbsp;Bénédicte Héron,&nbsp;Florence Dalbies,&nbsp;Bérengère Cador,&nbsp;Anne-Sophie Guemann,&nbsp;Francis Gaches,&nbsp;Bénédicte Hivert,&nbsp;Vanessa Leguy-Seguin,&nbsp;Agathe Masseau,&nbsp;Robin Deshayes,&nbsp;Yves-Marie Pers,&nbsp;Magali Pettazzoni,&nbsp;Soumeya Bekri,&nbsp;Catherine Caillaud,&nbsp;Edouard Le Guillou,&nbsp;Marie Szymanowski,&nbsp;Leonardo Astudillo,&nbsp;Wladimir Mauhin,&nbsp;Yann Nadjar,&nbsp;Christine Serratrice,&nbsp;Marc G. Berger,&nbsp;Fabrice Camou,&nbsp;Nadia Belmatoug,&nbsp;Jérôme Stirnemann,&nbsp;French Evaluation of Gaucher Disease Treatment Committee","doi":"10.1002/jimd.70037","DOIUrl":"https://doi.org/10.1002/jimd.70037","url":null,"abstract":"<p>Gaucher disease (GD) is a rare autosomal-recessive lysosomal disorder caused by glucocerebrosidase deficiency. In this study, we described the epidemiology of GD in France over more than three decades. The French GD registry (FGDR) includes all known patients with GD in France. We described patients' characteristics, and estimated the incidence, prevalence, and standardized mortality ratios of GD. We compared the evolution of diagnostic methods, diagnosis delays, and treatment over time, and assessed the incidence of bone events, malignancies, and Parkinson's disease. Between 1980 and 2024, 706 confirmed GD were included. In 2024, 447 patients were alive (413 type 1, 34 type 3). GD incidence was 0.21/1 000 000 PY, and GD prevalence was 0.61 and 0.05/100 000 inhabitants for type 1 and 3, respectively. The standardized mortality ratio was 0.70 for type 1 GD and 16.23 for type 3 GD. Over time, we observed a decrease in the delay between first symptoms and diagnosis (5.4 years before 2000; 0.8 after 2020; <i>p</i> = 0.001), with enzyme assays becoming the primary diagnostic method, a reduction in splenectomies, and a gradual increase in the use of substrate reduction therapy in type 1 GD. The incidences of bone events, malignancies, and Parkinson's disease were 23, 2.7, and 1.07 per 1000 person-years, respectively. This study provides updated epidemiological data on GD in France, showing improvements in disease knowledge, faster and less invasive diagnoses, and reassuring outcomes for type 1 GD, with lower mortality and a relatively low incidence of malignancies and Parkinson's disease.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 3","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}