Journal of Inherited Metabolic Disease最新文献

{"title":"Spermidine Treatment Improves GRIN2B Loss-Of-Function, A Primary Disorder of Glutamatergic Neurotransmission","authors":"A. Santos-Gómez,&nbsp;N. Juliá-Palacios,&nbsp;A. Rejano-Bosch,&nbsp;R. Marí-Vico,&nbsp;F. Miguez-Cabello,&nbsp;M. Masana,&nbsp;D. Soto,&nbsp;M. Olivella,&nbsp;À. García-Cazorla,&nbsp;X. Altafaj","doi":"10.1002/jimd.70015","DOIUrl":"https://doi.org/10.1002/jimd.70015","url":null,"abstract":"<p>GRIN-related disorders (GRD) developmental and epileptic encephalopathies (DEEs) display a clinical spectrum including developmental delay, hypotonia, intellectual disability, epilepsy, and autistic traits. The presence of de novo pathogenic variants in the <i>GRIN</i> genes alters the <i>N</i>-methyl D-aspartate receptor (NMDAR) function, with a genotype-phenotype relationship. Despite recent advances to elucidate GRD pathophysiological mechanisms and to find treatments, to date, GRD therapeutic arms are still scarce and with limited efficacy. Herein, we investigated whether the natural polyamine spermine—positive allosteric modulators of GluN2B subunit-containing NMDARs—or its precursor spermidine might rescue NMDAR hypofunctionality. In heterologous cell systems, administration of spermine potentiated wild-type and loss-of-function (LoF) NMDAR-mediated currents and attenuated synaptic density deficits. Functionally, the putative therapeutic benefit of spermidine (spermine precursor) was assessed in constitutive <i>Grin2b</i>^+/− heterozygous mice, a GRIN2B-LoF genetic murine model recapitulating GRD-like synaptic, motor, and cognitive alterations. Chronic spermidine administration in young adult <i>Grin2b</i>^+/− mice partially rescued hippocampal long-term potentiation deficits in hippocampal slices of <i>Grin2b</i>^+/− mice, supporting the cognitive improvement observed in behavioral phenotyping. Based on these preclinical findings, a case study was conducted in two pediatric patients harboring mild GRIN2B-LoF variants. Importantly, in line with preclinical findings, 18 months of spermidine treatment resulted in the amelioration of adaptive behavior (notably in the younger treated patient), with the absence of noticeable side effects. Overall, our findings provide both preclinical and clinical data supporting the benefit of spermidine for the treatment of GRD in individuals harboring GRIN2B-LoF variants.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530056","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":"Phosphoinositide Metabolism: Biochemistry, Physiology and Genetic Disorders","authors":"Francis Rossignol,&nbsp;Foudil Lamari,&nbsp;Grant A. Mitchell","doi":"10.1002/jimd.70008","DOIUrl":"https://doi.org/10.1002/jimd.70008","url":null,"abstract":"<p>Phosphatidylinositol, a glycerophospholipid with a <i>myo</i>-inositol head group, can form seven different phosphoinositides (PItds) by phosphorylation at inositol carbons 3, 4 and/or 5. Over 50 kinases and phosphatases participate in PItd metabolism, creating an interconnected PItd network that allows for precise temporal and spatial regulation of PItd levels. We review paradigms of PItd action, including (1) the establishment of subcellular organelle identity by the acquisition of specific PItd signatures, permitting regulation of key processes of cell biology including trafficking (exocytosis, clathrin-dependent and -independent endocytosis, formation and function of membrane contact sites, cytoskeletal remodeling), (2) signaling through phospholipase C cleavage of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate and DAG, and (3) roles of PItds in molecular transport at membrane contact sites. To date, variants in 34 genes of PItd metabolism account for at least 41 distinguishable monogenic conditions. Clinical presentations of these disorders produce a broad and often multisystemic spectrum of effects. The nervous system is often involved, and muscular, immunological, skeletal, renal, ophthalmologic and dermatologic features occur in several conditions. Some syndromes involving PItd metabolism can be distinguished clinically, but most diagnoses currently result from broad molecular diagnostic testing performed for the patient's presenting clinical complaint. Genetic disorders of PItd metabolism are a broad, expanding and challenging category of inborn errors. Challenges include improved documentation of the clinical spectra, development of broad biochemical diagnostic methods for these conditions and better understanding of the PItd networks in different cells and subcellular compartments necessary for the development of disease-specific therapies.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530057","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":"“Trafficking Disorders: Phenotypical Similarities and Differences With Other IMDs”","authors":"Ángeles García-Cazorla,&nbsp;Eva Morava,&nbsp;Jean-Marie Saudubray","doi":"10.1002/jimd.70004","DOIUrl":"https://doi.org/10.1002/jimd.70004","url":null,"abstract":"<div>\u0000 \u0000 <p>Cell trafficking disorders (CTD) are genetic defects in complex molecules and correspond to the largest category of IEM with mutations in more than 370 genes described. They are still poorly recognized as a global entity but rather seen as isolated rare diseases by non-metabolic specialists. Complex lipid metabolism (mostly phospholipids, sphingolipids, and non-mitochondrial fatty acids) is tightly associated with cell trafficking and interactions between organelles at the membrane contact sites. Accordingly, from a clinical point of view CTD presents with multisystem manifestations that may overlap and mimic mitochondrial and other complex molecule disorders such as peroxisomal, lysosomal defects, CDG, or autophagy disorders. The nervous system is especially vulnerable and neurological presentations are prominent, but CTD targets any organ at any age. Interestingly the involvement of the immune system is particularly characteristic of CTD and rarely (or at least little described so far) in other categories of IEM. Most CTD are progressive disorders, except for CDG. They may have “metabolic crises” mimicking disorders of intermediary and energy metabolism for which emergency protocols have been developed. They are generally diagnosed by exome sequencing. Relatively few biomarkers are available.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466293","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":"Effectiveness of Kidney Transplantation in Treating Alkaptonuric Skin Ochronosis","authors":"Aude Belbézier,&nbsp;Mathilde Tardieu,&nbsp;Nathalie Sturm,&nbsp;Julie Charles,&nbsp;Marie-Thérèse Leccia","doi":"10.1002/jimd.70012","DOIUrl":"https://doi.org/10.1002/jimd.70012","url":null,"abstract":"","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455944","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":"Amino Acid Metabolism and Immune Dysfunction in Urea Cycle Disorders: T and B Cell Perspectives","authors":"Betul Gemici Karaaslan,&nbsp;Ayca Kiykim,&nbsp;Nihan Burtecene,&nbsp;Meltem Gokden,&nbsp;Mehmet Serif Cansever,&nbsp;Duhan Hopurcuoglu,&nbsp;Gökçe Nuran Cengiz,&nbsp;Birol Topcu,&nbsp;Tanyel Zubarioğlu,&nbsp;Ertugrul Kiykim,&nbsp;Haluk Cokuğras,&nbsp;Ayse Cigdem Aktuglu Zeybek","doi":"10.1002/jimd.70009","DOIUrl":"https://doi.org/10.1002/jimd.70009","url":null,"abstract":"<p>Urea cycle disorders (UCDs) are a group of genetic metabolic conditions characterized by enzyme deficiencies responsible for detoxifying ammonia. Hyperammonemia, the accumulation of intermediate metabolites, and a deficiency of essential amino acids—due to a protein-restrictive diet and the use of ammonia scavengers—can increase the risk of infections, particularly during metabolic crises. While the underlying mechanisms of immune suppression are still being fully elucidated, hyperammonemia may impair the function of immune cells, particularly T cells and macrophages, inhibiting the proliferation of T cells and cytokine production. Arginine, which is essential for T-cell activation and function, may also be limited in these patients, and its depletion can increase their vulnerability to infections. Twenty-four UCD patients and 31 healthy donors were recruited for the study. Peripheral lymphocyte subset analysis, intracellular protein and cytokine staining, and proliferation assays were performed by flow cytometry. Amino acid levels were measured using the HPLC method. The UCD patients exhibited low lymphocyte-proliferation capacity in both proximal and distal defects in response to phytohaemagglutinin (PHA) and anti-CD2, anti-CD3, and anti-CD28 (CD-mix), which was lower than healthy controls. Proximal-UCD patients exhibited a significantly higher response for IFN-γ compared to both distal-UCD patients and healthy controls. The different amino acids in the culture medium were changed significantly in the groups. This study highlights significant immune dysfunctions in UCD patients, particularly impaired T-cell proliferation and altered amino acid metabolism. Proximal UCD patients exhibited a higher IFN-γ response, indicating a potential for hyperinflammation. Despite this, infection rates did not significantly differ between proximal UCD and distal UCD patients, although distal UCD patients had higher hospitalization rates. Amino acid analysis revealed distinct metabolic disruptions, emphasizing the complex interplay between metabolism and immune function. These findings suggest that UCDs cause profound immune alterations, necessitating further research to develop targeted therapeutic strategies.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423728","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":"Emergency Management of Intoxication-Type Inherited Metabolic Disorders","authors":"J. Dexter Tarr,&nbsp;Andrew A. M. Morris","doi":"10.1002/jimd.70007","DOIUrl":"https://doi.org/10.1002/jimd.70007","url":null,"abstract":"<p>In many intoxication-type inherited metabolic disorders, the accumulation of the toxic chemical can cause acute life-threatening emergencies. Sometimes this is the inevitable consequence of a severe metabolic defect, but it is often triggered by catabolism. In this article, we consider the acute management when these conditions cause encephalopathy, seizures, stroke-like episodes, thromboses, liver failure, cardiac failure, arrhythmias and rhabdomyolysis. Treatment is available for most intoxication-type disorders, though it is seldom entirely satisfactory. The emergency management involves general measures for the immediate problem (such as liver failure, thrombosis or an arrhythmia) and specific treatment for the metabolic disorder. The latter usually aims to reduce the accumulation of the toxic small molecule. Often this involves preventing or reversing catabolism. Sometimes the formation of the toxic chemical can be reduced by removing dietary precursors, by diverting precursors to alternative pathways, or by inhibiting an earlier step in the affected pathway. Another strategy is to remove the toxic chemical by binding it to a drug or by extracorporeal blood purification. Occasionally, the block in the pathway can be ameliorated and some disorders, specific treatment may prevent the consequences of the accumulating chemical. Despite all these treatment strategies, outcomes are often disappointing, particularly if an intoxication disorder first presents as an emergency. Newborn screening has greatly improved the prognosis for some disorders. For others, outcomes can only be improved by earlier recognition and treatment.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423800","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":"Reshaping the Treatment Landscape of a Galactose Metabolism Disorder","authors":"M. Estela Rubio-Gozalbo,&nbsp;E. Naomi Vos,&nbsp;Isabel Rivera,&nbsp;Kent Lai,&nbsp;Gerard T. Berry","doi":"10.1002/jimd.70013","DOIUrl":"https://doi.org/10.1002/jimd.70013","url":null,"abstract":"<p>The Leloir pathway was elucidated decades ago, unraveling how galactose is metabolized in the body. Different inborn errors of metabolism in this pathway are known, the most frequent and well-studied being Classic Galactosemia (CG) (OMIM 230400) due to pathogenic variants in the <i>GALT</i> gene. Substrate reduction using dietary restriction of galactose is currently the only available treatment option. Although this burdensome diet resolves the life-threatening clinical picture in neonates, patients still face long-term complications, including cognitive and neurological deficits as well as primary ovarian insufficiency. Emerging therapies aim to address these challenges on multiple fronts: (1) restoration of GALT activity with nucleic acid therapies, pharmacological chaperones, or enzyme replacement; (2) influencing the pathological cascade of events to prevent accumulation of metabolites (Galactokinase 1 (GALK1) inhibitors, aldose reductase inhibitors), address myo-inositol deficiency, or alleviate cellular stress responses; (3) substrate reduction with synthetic biotics or galactose uptake inhibitors to eliminate the need for lifelong diet; and (4) novel approaches to mitigate existing symptoms, such as non-invasive brain stimulation and reproductive innovations. Early, personalized intervention remains critical for optimizing patient outcomes. We review the advances in the development of different treatment modalities for CG and reflect on the factors that need to be considered and addressed to reshape the landscape of treatment.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423971","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":"C1GALT1C1-Associated Mosaic Disorder of Glycosylation in a Female","authors":"Rajindra P. Aryal,&nbsp;Aditya Ramanujan,&nbsp;Camille Bucci,&nbsp;Christian Neckelmann,&nbsp;Jamie Heimburg-Molinaro,&nbsp;Sandra F. Cummings,&nbsp;Florian Erger,&nbsp;Bodo B. Beck,&nbsp;Laurie H. Seaver,&nbsp;Richard D. Cummings","doi":"10.1002/jimd.70006","DOIUrl":"https://doi.org/10.1002/jimd.70006","url":null,"abstract":"<p>Cosmc, encoded by the X-linked <i>C1GALT1C1</i>, is a molecular chaperone in the endoplasmic reticulum and a master regulator of O-glycosylation of mammalian glycoproteins. Recently, we described a germline mutation in <i>C1GALT1C1</i> in two male patients, giving rise to a congenital disorder of glycosylation—<i>COSMC</i>-CDG. Here, we have identified a female patient with a <i>de novo</i> mosaic variant in <i>C1GALT1C1</i> (c.202C&gt;T, p.Arg68*), which results in a truncated and nonfunctional form of Cosmc (Cosmc-R68). The patient is mosaic, as ~27% of her buccal cells carry the mutation. The patient is now a 5-year old who presented with nonimmune hydrops fetalis. As Cosmc is essential for the generation of normal O-glycans through regulating T-synthase activity, thereby enabling the formation of the universal Core 1 O-glycan Galβ1-3GalNAcα1-Ser/Thr (T-antigen), the loss of Cosmc leads to the expression of the unusual precursor O-glycan termed Tn-antigen (CD175) (GalNAcα1-Ser/Thr). Owing to the mutational mosaicism, only a significant minority of cells would exhibit abnormal O-glycosylation. Analysis of red blood cells (RBCs), leukocytes, and serum from this patient indicated reduced expression of Cosmc and T-synthase proteins and lower T-synthase activity. Consistent with these findings, we observed reduced normal O-glycans in serum glycoproteins and RBCs from the patient, along with elevated expression of the Tn-antigen in serum glycoproteins compared to controls. This case represents the first description of a true mosaic loss-of-function variant in <i>C1GALT1C1</i>, that is, one that occurred postzygotically during embryogenesis, and raises interesting questions about the role of O-glycosylation during fetal development and its consequences on the clinical presentation.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404536","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":"Human Milk Feeding in Inherited Metabolic Disorders: A Systematic Review of Growth, Metabolic Control, and Neurodevelopment Outcomes","authors":"Fatma Ilgaz,&nbsp;Alexander Höller,&nbsp;Cyril Marsaux,&nbsp;Sandra Banta-Wright,&nbsp;Turgay Coşkun,&nbsp;Kelly A. Dingess,&nbsp;Monika Jörg-Streller,&nbsp;Camille Newby,&nbsp;Rani Singh,&nbsp;Bernd Stahl,&nbsp;Clare Szwec,&nbsp;Annemiek van Wegberg,&nbsp;Willie Woestenenk,&nbsp;Anita MacDonald,&nbsp;Daniela Karall","doi":"10.1002/jimd.70001","DOIUrl":"https://doi.org/10.1002/jimd.70001","url":null,"abstract":"<p>Human milk (HM) is the optimal source of nutrition for infants. Yet the suitability of HM macronutrient composition, paired with the challenge of regulating HM intake, may deserve some consideration for infants with inherited metabolic disorders (IMDs) requiring restrictive and controlled dietary management. Except for classic galactosemia, HM feeding is expected to be feasible, allowing infants to maintain metabolic stability, while growing and developing optimally. However, information about HM feeding in nonphenylketonuria (PKU) literature is scarce. In this systematic review, 52 studies were included, representing 861 infants (86% PKU) receiving HM after IMD diagnosis (mean duration 4–10 months depending on the IMD). For non-PKU IMDs (e.g., other amino acidopathies, urea cycle disorders, organic acidemias, fatty acid oxidation disorders), outcomes of HM feeding were available for few infants, except for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (<i>n</i> = 48). In PKU, HM feeding combined with phenylalanine-free formula, led to adequate metabolic control (25 studies), growth (15 studies), and neurodevelopment (10 studies). For other IMDs, more evidence is required, but the limited data suggest that HM feeding is possible, with attentive monitoring and disease-specific formula supplementation where applicable. In MCAD deficiency, ensuring adequate HM intake is essential, as symptoms were more frequently reported in exclusively breastfed infants. No IMD-specific articles were found on the relationship between HM feeding and many other outcomes of interest (e.g., immune status or comorbidity risk later in life). With the exception of galactosemia, HM feeding is expected to benefit infants with IMD. More data should be published for IMDs other than PKU.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248883","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":"The Frequencies of Different Inborn Errors of Metabolism in Adult Metabolic Centres: 10 Years Later, Another Report From the SSIEM Adult Metabolic Physicians Group","authors":"Michel Tchan,&nbsp;Anna Lehman,&nbsp;Laura van Dussen,&nbsp;Janneke G. Langendonk,&nbsp;Mirian C. H. Janssen,&nbsp;Mirjam Langeveld,&nbsp;Elaine Murphy,&nbsp;Bryony Ryder,&nbsp;Emma Glamuzina,&nbsp;Martin Merkel,&nbsp;Annalisa Sechi,&nbsp;Jean-Baptiste Arnoux,&nbsp;Fanny Mochel,&nbsp;Gonnie Alkemade,&nbsp;Francois Maillot,&nbsp;Elsa Kaphan,&nbsp;Karin Mazodier,&nbsp;Quentin Thomas,&nbsp;Vanessa Leguy-Seguin,&nbsp;Cecilia Marelli","doi":"10.1002/jimd.70005","DOIUrl":"https://doi.org/10.1002/jimd.70005","url":null,"abstract":"<div>\u0000 \u0000 <p>There are still few centres, which specialise in the care of adults with inborn errors of metabolism (IEM). All physicians who participated in the SSIEM adult metabolic physicians group paper in 2014 were contacted to provide updated data on their IEM patients. Fifteen adult centres responded to our survey with information on their patients. Nine thousand, six hundred fifty-one patients were included in the final cohort, compared with 6 182 in the previous analysis. There were 394 separate diagnoses. The most common diseases were phenylketonuria (19.6%), mitochondrial disorders (12.3%) and lysosomal storage disorders such as Fabry disease (20.1% of LSD's), Pompe disease (3.1%), and Gaucher disease (2.8%). Among the disorders that can present with acute metabolic decompensation, the urea cycle disorders (4.0%), were most common (ornithine transcarbamylase deficiency 2.6%), followed by maple syrup urine disease (1.1%) and glycogen storage disease type I (0.7%). Patients were frequently diagnosed as adults, particularly those with mitochondrial disease and lysosomal storage disorders. Many patients are only diagnosed in adulthood (&gt; 40%) and the cohort is increasing substantially with 9 651 patients included in the final analysis (34% increase compared to our original paper). Thus reinforcing the need for adult specialists to be trained in this area.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248884","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}