Journal of Inherited Metabolic Disease最新文献

{"title":"Positive Clinical, Neuropsychological, and Metabolic Impact of Liver Transplantation in Patients With Argininosuccinate Lyase Deficiency","authors":"Barbara Siri,&nbsp;Benedetta Greco,&nbsp;Diego Martinelli,&nbsp;Sara Cairoli,&nbsp;Alessia Guarnera,&nbsp;Daniela Longo,&nbsp;Antonio Napolitano,&nbsp;Chiara Parrillo,&nbsp;Lucilla Ravà,&nbsp;Raffaele Simeoli,&nbsp;Gionata Spagnoletti,&nbsp;Roberta Taurisano,&nbsp;Silvio Veraldi,&nbsp;Andrea Pietrobattista,&nbsp;Marco Spada,&nbsp;Carlo Dionisi-Vici","doi":"10.1002/jimd.12843","DOIUrl":"10.1002/jimd.12843","url":null,"abstract":"<p>Liver transplantation (LTx) is increasingly used in Urea Cycle Defects (UCDs) to prevent recurrent hyperammonemia and related neurological irreversible injury. Among UCDs, argininosuccinate lyase deficiency (ASLD) has a more complex phenotype than other UCDs, with long-term neurocognitive deficits. Therefore, the role of LTx in ASLD is still debated. The impact of LTx on nine patients with early-onset ASLD was assessed through pre- and post-LTx clinical, neuropsychological, MRI and biochemical evaluations. After LTx, no episodes of metabolic decompensations were reported. Neuropsychological evaluations documented significant improvement in cognitive/developmental functioning especially in patients transplanted in early childhood. Improvements were also highlighted in daily living skills and emotional-behavioral problems, with a reduction in attention disturbances and somatic complaints. Movement disorders resolved after LTx in patient transplanted in early childhood. Any patients developed epilepsy with stability of EEG alterations after LTx. A positive effect of LTx on other disease-related outcomes such as growth, diet, medications, hospitalizations, and long-term ASLD-related complications was highlighted. The primary biomarker argininosuccinic acid dramatically reduced in plasma after transplantation with a decreasing trend in CSF at long-term follow-up. Moreover, health-related quality of life improved after LTx, especially when assessed through MetabQoL, a tool designed for intoxication diseases such as ASLD. In conclusion, our study showed a global beneficial impact of LTx in early-onset ASLD patients to avoid episodes of hyperammonemia, and improve neurocognitive outcome, adaptive and behavioral deficits when performed in early childhood with a dramatic benefit in terms of quality of life.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950220","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 Insights Into Gyrate Atrophy of the Choroid and Retina (GACR): A Cohort Study","authors":"Berith M. Balfoort,&nbsp;Filip Van den Broeck,&nbsp;Camiel J. F. Boon,&nbsp;Martijn C. G. J. Brouwers,&nbsp;Roselie M. H. Diederen,&nbsp;Preet Dhillon,&nbsp;GACR “Bird's Eye View” Consortium,&nbsp;Peter M. van Hasselt,&nbsp;Bregje Jaeger,&nbsp;Jessica S. Karuntu,&nbsp;Alexander J. M. Rennings,&nbsp;Francjan J. van Spronsen,&nbsp;Corrie Timmer,&nbsp;Margreet A. E. M. Wagenmakers,&nbsp;Julie De Zaeytijd,&nbsp;Bart P. Leroy,&nbsp;Andreas Schulze,&nbsp;Clara D. van Karnebeek,&nbsp;Marion M. Brands","doi":"10.1002/jimd.12842","DOIUrl":"10.1002/jimd.12842","url":null,"abstract":"<p>Gyrate atrophy of the choroid and retina (GACR, OMIM #258870) is a rare inherited metabolic disorder characterized by progressive chorioretinal degeneration and hyperornithinemia. Current therapeutic modalities potentially slow disease progression but are not successful in preventing blindness. To allow for trial development, increased knowledge of the clinical phenotype and current therapeutic outcomes is required. In this study, we analyzed 27 patients with GACR. The median age at inclusion was 24 years (range 8–58), with a median age at diagnosis of 14 years (range 0–42). Symptoms began at a mean age of 9 years (range 0–21). Mixed-models analysis showed a significant association between dietary natural protein intake and plasma ornithine levels. Ornithine increased significantly with age, independent of dietary natural protein intake. We found no statistically significant association between ornithine levels and best-corrected visual acuity over time. Patients who started a natural protein-restricted diet below 10 years of age had better VF outcomes compared to patients that started at a later age. MR spectroscopy was used to asses cerebral creatine deficiency, which was present in 15/20 patients, of whom 10 were supplemented with creatine at the time. Finally, using the Michigan Retinal Degeneration Questionnaire, we provided a first insight into the vision-related disability reported by patients with GACR and showed that higher foveal sensitivity was associated with less perceived disability. To conclude, this study provides insights into the phenotype, genotype, biochemistry, and treatment effects of GACR, which can be used for care pathways and clinical trial design.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950217","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":"Diffusion tensor imaging with free-water correction reveals distinctions between severe and attenuated subtypes in Mucopolysaccharidosis type I","authors":"Alena Svatkova,&nbsp;Ofer Pasternak,&nbsp;Julie B. Eisengart,&nbsp;Kyle D. Rudser,&nbsp;Petr Bednařík,&nbsp;Bryon A. Mueller,&nbsp;Kathleen A. Delaney,&nbsp;Elsa G. Shapiro,&nbsp;Chester B. Whitley,&nbsp;Igor Nestrašil","doi":"10.1002/jimd.12830","DOIUrl":"10.1002/jimd.12830","url":null,"abstract":"<p>Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disorder leading to deleterious brain effects. While animal models suggested that MPS I severely affects white matter (WM), whole-brain diffusion tensor imaging (DTI) analysis was not performed due to MPS-related morphological abnormalities. 3T DTI data from 28 severe (MPS IH, treated with hematopoietic stem cell transplantation—HSCT), 16 attenuated MPS I patients (MPS IA) enrolled under the study protocol NCT01870375, and 27 healthy controls (HC) were analyzed using the free-water correction (FWC) method to resolve macrostructural partial volume effects and unravel differences in DTI metrics accounting for microstructural abnormalities. FWC analysis in MPS IH compared to HC revealed higher free-water fraction (FWF) in all WM regions with increased radial (RD) and mean diffusivity (MD). Higher RD, MD, and FWF in cingulate and FWF in temporal WM were observed in MPS IA relative to HC. FWF and RD in the corpus callosum (CC) were higher in MPS IH than in MPS IA. Reaction time was correlated with fractional anisotropy (FA) in frontal and parietal WM in MPS IH. FA in temporal and central WM correlated with d-prime in MPS IA. The HSCT age was related to FA in parietal WM and FWF in frontal WM in MPS IH. FWC delineated subtype-specific WM microstructural abnormalities linked to myelination that were more extensive in MPS IH than IA, with CC findings being a key differentiator between subtypes. Earlier age at HSCT was related to preserved WM microstructure in the brain of MPS IH patients. Free water-corrected DTI distinguishes severe and attenuated MPS I patients and reveals a relationship between attention, age at HSCT, and white matter microstructure.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950216","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":"Biological Basis of Cell Trafficking: A General Overview","authors":"Helena Gimeno-Agud,&nbsp;Yaiza Díaz-Osorio,&nbsp;Alfonso Oyarzábal","doi":"10.1002/jimd.12839","DOIUrl":"10.1002/jimd.12839","url":null,"abstract":"<p>Cell trafficking is a tightly regulated biological process for the exchange of signals and metabolites between cell compartments, including four main processes: membrane trafficking (transport of membrane-bound vesicles), autophagy, transport along the cytoskeleton, and membrane contact sites. These processes are cross-sectional to cellular functions, ranging from the transportation of membrane proteins, membranes, and organelles to the elimination of damaged proteins and organelles. In consequence, cell trafficking is crucial for cell survival and homeostasis, serving as a cornerstone for cellular communication and facilitating interactions both with the surrounding environment and between different organelles. Disorders of cell trafficking are clinically and pathophysiological diverse and complex and form the largest group in the recent International Classification of Inherited Metabolic Disorders (ICIMD). In this review, we explore the four categories of cell trafficking and the biological principles that drive these processes. Instead of delving profoundly into each pathway, as comprehensive reviews on those topics already exist, we offer a broad overview of the molecular mechanisms behind cell trafficking, providing a foundational understanding to ease their entry into this subject and enhance comprehension of the other articles featured in this Special Issue.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932148","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":"Valine Restriction Extends Survival in a Drosophila Model of Short-Chain Enoyl-CoA Hydratase 1 (ECHS1) Deficiency","authors":"Sarah Mele,&nbsp;Felipe Martelli,&nbsp;Christopher K. Barlow,&nbsp;Grace Jefferies,&nbsp;Sebastian Dworkin,&nbsp;John Christodoulou,&nbsp;Ralf B. Schittenhelm,&nbsp;Matthew D. W. Piper,&nbsp;Travis K. Johnson","doi":"10.1002/jimd.12840","DOIUrl":"10.1002/jimd.12840","url":null,"abstract":"<div>\u0000 \u0000 <p>Short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) is a rare genetic disorder caused by biallelic pathogenic variants in the <i>ECHS1</i> gene. ECHS1D is characterised by severe neurological and physical impairment that often leads to childhood mortality. Therapies such as protein and single nutrient-restricted diets show poor efficacy, whereas the development of new treatments is hindered by the low prevalence of the disorder and a lack of model systems for treatment testing. Here, we report on the establishment of a <i>Drosophila</i> model of ECHS1D. Flies carrying mutations in <i>Echs1</i> (CG6543) were characterised for their physical and metabolic phenotypes, and dietary intervention to improve fly model health was explored. The <i>Echs1</i> null larvae recapitulated human ECHS1D phenotypes including poor motor behaviour and early mortality and could be rescued by the expression of a human <i>ECHS1</i> transgene. We observed that both restriction of valine in isolation, or all branched-chain amino acids (BCAAs—leucine, isoleucine and valine) together, extended larval survival, supporting the idea that reducing BCAA pathway catabolic flux is beneficial in this disorder. Further, metabolic profiling revealed substantial changes to carbohydrate metabolism, suggesting that <i>Echs1</i> loss causes widespread metabolic dysregulation beyond valine metabolism. The similarities between <i>Drosophila</i> and human ECHS1D suggest that the fly model is a valuable animal system in which to explore mechanisms of pathogenesis and novel treatment options for this disorder.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895412","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":"Aldolase B Deficient Mice Are Characterized by Hepatic Nucleotide Sugar Abnormalities","authors":"Amée M. Buziau,&nbsp;Dirk J. Lefeber,&nbsp;D. Cassiman,&nbsp;M. Estela Rubio-Gozalbo,&nbsp;Hanneke Kwast,&nbsp;Dean R. Tolan,&nbsp;Casper G. Schalkwijk,&nbsp;Martijn C. G. J. Brouwers","doi":"10.1002/jimd.12836","DOIUrl":"10.1002/jimd.12836","url":null,"abstract":"<p>Hereditary fructose intolerance (HFI) is characterized by liver damage and a secondary defect in N-linked glycosylation due to impairment of mannose phosphate isomerase (MPI). Mannose treatment has been shown to be an effective treatment in a primary defect in MPI (i.e., MPI-CDG), which is also characterized by liver damage. Therefore, the aims of this study were to determine: (1) hepatic nucleotide sugar levels, and (2), the effect of mannose supplementation on hepatic nucleotide sugar levels and liver fat, in a mouse model for HFI. Aldolase B deficient mice (<i>Aldob</i>^{<i>−/−</i>}) were treated for four weeks with 5% mannose via the drinking water and compared to <i>Aldob</i>^{<i>−/</i>−} mice and wildtype mice treated with regular drinking water. We found that hepatic GDP-mannose and hepatic GDP-fucose were lower in water-treated <i>Aldob</i>^{<i>−/</i>−} mice when compared to water-treated wildtype mice (<i>p</i> = 0.002 and <i>p</i> = 0.002, respectively), consistent with impaired N-linked glycosylation. Of interest, multiple other hepatic nucleotide sugars not involved in N-linked glycosylation, such as hepatic UDP-glucuronic acid, UDP-xylose, CMP-<i>N</i>-acetyl-beta-neuraminic acid, and CDP-ribitol (<i>p</i> = 0.002, <i>p</i> = 0.003, <i>p</i> = 0.002, <i>p</i> = 0.002), were found to have altered levels as well. However, mannose treatment did not correct the reduction in hepatic GDP-mannose levels, nor was liver fat affected. <i>Aldob</i>^{<i>−/</i>−} mice are characterized by hepatic nucleotide sugar abnormalities, but these were not abrogated by mannose treatment. Future studies are needed to identify the underlying mechanisms responsible for the abnormal hepatic nucleotide sugar pattern and intrahepatic lipid accumulation in HFI.</p><p><b>Trial Registration:</b> PCT ID: PCTE0000340, this animal experiment is registered at (https://preclinicaltrials.eu/).</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895409","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":"Altered lipid profile and reduced neuronal support in human induced pluripotent stem cell-derived astrocytes from adrenoleukodystrophy patients","authors":"Roberto Montoro Ferrer,&nbsp;Yorrick R. J. Jaspers,&nbsp;Inge M. E. Dijkstra,&nbsp;Nicole Breeuwsma,&nbsp;Jan-Bert van Klinken,&nbsp;Cato Romero,&nbsp;Marc Engelen,&nbsp;Stephan Kemp,&nbsp;Vivi M. Heine","doi":"10.1002/jimd.12832","DOIUrl":"10.1002/jimd.12832","url":null,"abstract":"<p>X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder resulting from pathogenic variants in the <i>ABCD1</i> gene that primarily affects the nervous system and is characterized by progressive axonal degeneration in the spinal cord and peripheral nerves and leukodystrophy. Dysfunction of peroxisomal very long-chain fatty acid (VLCFA) degradation has been implicated in ALD pathology, but the impact on astrocytes, which critically support neuronal function, remains poorly understood. Fibroblasts from four ALD patients were reprogrammed to generate human-induced pluripotent stem cells (hiPSC). hiPSC-derived astrocytes were generated to study the impact of ALD on astrocytic fatty acid homeostasis. Our study reveals significant changes in the lipidome of ALD hiPSC-derived astrocytes, characterized by an enrichment of VLCFAs across multiple lipid classes, including triacylglycerols, cholesteryl esters, and phosphatidylcholines. Importantly, ALD hiPSC-derived astrocytes not only exhibit intrinsic lipid dysregulation but also affect the dendritic tree complexity of neurons in co-culture systems. These findings highlight the cell-autonomous effects of pathogenic variants in the ABCD1 protein on astrocytes and their microenvironment, shed light on potential mechanisms underlying ALD neuropathology, and underscore the critical role of astrocytes in neuronal health.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864572","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":"Beyond neuropsychological tests: AI speech analysis in PKU","authors":"Susan E. Waisbren,&nbsp;Raquel Norel,&nbsp;Carla Agurto,&nbsp;Shifali Singh,&nbsp;Zoe A. Connor,&nbsp;Marina G. Ebrahim,&nbsp;Guillermo A. Cecchi","doi":"10.1002/jimd.12831","DOIUrl":"10.1002/jimd.12831","url":null,"abstract":"<p>Phenylketonuria (PKU) is a rare inherited metabolic disorder characterized by toxic phenylalanine (Phe) concentrations in blood and brain. State-of-the-art analyses of speech detected a dimension of verbal discourse providing insights that extend beyond those captured by existing paradigms to measure performance associated with biochemical markers in PKU. The Cookie Theft Picture Task provided a standardized stimulus for eliciting spontaneous speech from 42 adults with PKU and 41 adults without PKU. Subtests measuring language and memory from the Wechsler Adult Intelligence Scale-Fourth Edition showed no differences between the groups and no correlations with biomarkers in PKU. In contrast, AI analyses of responses to the Cookie Theft Task revealed significant differences between the PKU and non-PKU groups on 23 linguistic features. Using multidimensional scaling (MDS), these features were aggregated into a single quantifiable Dimension 1 that significantly correlated with biomarkers. When extreme examples of Dimension 1 were presented to chatGPT, the differences noted reflected attention to detail, clarity in word choice, expression cohesion, contextual awareness and emotion recognition. We subsequently defined Dimension 1 as Proficiency in Verbal Discourse. This novel measure elucidated discourse styles possibly associated with suboptimal achievement and learning disabilities, often reported in PKU. In summary, AI captured a characteristic associated with metabolic status undetectable through traditional neuropsychological measures. Future studies will expand upon this novel paradigm, leveraging speech AI to quantify meaningful aspects of everyday functioning and possibly provide information for management decisions. Once validated, this measure holds promise for extension to other rare diseases and incorporation into clinical trials.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846772","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":"Diagnosis, treatment, management and monitoring of patients with tyrosinaemia type 1: Consensus group recommendations from the German-speaking countries","authors":"Anibh M. Das,&nbsp;Diana Ballhausen,&nbsp;Dorothea Haas,&nbsp;Johannes Häberle,&nbsp;Tobias Hagedorn,&nbsp;Cecilia Janson-Mutsaerts,&nbsp;Nils Janzen,&nbsp;Johannes Sander,&nbsp;Peter Freisinger,&nbsp;Daniela Karall,&nbsp;Uta Meyer,&nbsp;Eberhard Mönch,&nbsp;Susanne Morlot,&nbsp;Stefanie Rosenbaum-Fabian,&nbsp;Sabine Scholl-Bürgi,&nbsp;Stephan vom Dahl,&nbsp;Natalie Weinhold,&nbsp;Jiri Zeman,&nbsp;Karin Lange","doi":"10.1002/jimd.12824","DOIUrl":"10.1002/jimd.12824","url":null,"abstract":"<p>Hepatorenal tyrosinaemia (HT1) is an autosomal recessive disorder of tyrosine degradation resulting in hepatic and renal dysfunction, neurological sequelae may occur in some patients. The use of nitisinone (NTBC) has revolutionised treatment and outcome of this disorder. NTBC has to be combined with a low protein diet. While NTBC modulates the disease course in HT1 patients, several issues are open. Optimal dosage, doses per day, therapeutic range of NTBC concentration, mode of protein restriction and biomarkers are not well defined. HCC and neurocognitive deficits are long-term sequelae. Early diagnosis and treatment are essential to minimise the risk for these complications. Clinical guidance for management of HT1-patients is required. Randomised clinical studies are difficult in the presence of therapeutic options. We discussed these issues in a consensus group of 10 paediatricians, 1 adult hepatologist, 1 geneticist, 2 dieticians, 2 newborn screening specialists with experience in HT1, 1 psychologist and 2 representatives of a patient group from the German-speaking countries (DACH). Recommendations were based on scientific literature and expert opinion, also taking into account recent experience with newborn screening. There was strong consensus that newborn screening using succinylacetone (SA) and early treatment are essential for a good outcome. The dose of NTBC should be as low as possible without losing metabolic control. This has to be accompanied by a low protein diet, in some patients a simplified diet without calculation of protein intake. Specific education and psychosocial support are recommended. Indications for liver transplantation were defined. Monitoring shall include clinical findings, levels of SA, tyrosine, phenylalanine and NTBC in (dried) blood.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828943","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":"Executive and adaptive function impacts long-term outcomes for adults with maple syrup urine disease","authors":"Jessica I. Gold,&nbsp;Alanna Strong,&nbsp;Nina B. Gold,&nbsp;Marc Yudkoff,&nbsp;Dava Szalda,&nbsp;Sophia Jan,&nbsp;Lisa A. Schwartz,&nbsp;Rebecca Ganetzky","doi":"10.1002/jimd.12827","DOIUrl":"10.1002/jimd.12827","url":null,"abstract":"<p>Successful transition to independent adulthood requires intact executive and adaptive function. These neurocognitive domains are frequently impaired in inherited metabolic disorders (IMD), despite optimal management. For many IMDs, the impact of executive and adaptive dysfunction on long-term outcomes remains undefined. Standardized assessments linking neurocognitive status with functional outcomes are needed to improve prognostication and tailor support for affected emerging adults. Maple syrup urine disease (MSUD), a relatively prevalent IMD, is primarily diagnosed in the first week of life through newborn screening. Despite early intervention, executive and adaptive dysfunction persist. We designed a remote, interactive battery of neurocognitive and functional assessments for adults (≥21 years) with MSUD to correlate neurocognition and long-term outcomes. Participants were selectively recruited for racial, ethnic, socio-economic, and geographic diversity. Assessments completed by 28 adults with MSUD (82% diagnosed after symptom onset, 25% from minority communities) show a wide range in educational attainment, employment, and residence. Executive and adaptive function were significantly impaired in adults with MSUD compared to controls. Executive and adaptive deficits correlated negatively with educational attainment, employment, and obtaining skills needed for adult-oriented healthcare or independent living. Clinical history did not predict functional outcomes, but neurocognitive assessments suggest the benefits of pre-symptomatic diagnosis. Independent adulthood is attainable for individuals with MSUD. Routine assessment of neurocognition and interventions targeting executive and adaptive function may improve long-term functional outcomes in IMD.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801136","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}