Journal of Inherited Metabolic Disease最新文献

{"title":"Efficacy and safety of sapropterin before and during pregnancy: Final analysis of the Kuvan® Adult Maternal Paediatric European Registry (KAMPER) maternal and Phenylketonuria Developmental Outcomes and Safety (PKUDOS) PKU-MOMs sub-registries","authors":"François Feillet,&nbsp;Can Ficicioglu,&nbsp;Florian B. Lagler,&nbsp;Nicola Longo,&nbsp;Ania C. Muntau,&nbsp;Alberto Burlina,&nbsp;Friedrich K. Trefz,&nbsp;Francjan J. van Spronsen,&nbsp;Jean-Baptiste Arnoux,&nbsp;Kristin Lindstrom,&nbsp;Joshua Lilienstein,&nbsp;Gillian E. Clague,&nbsp;Richard Rowell,&nbsp;Barbara K. Burton,&nbsp;the KAMPER and PKUDOS investigators","doi":"10.1002/jimd.12724","DOIUrl":"10.1002/jimd.12724","url":null,"abstract":"<p>Infants born to mothers with phenylketonuria (PKU) may develop congenital abnormalities because of elevated phenylalanine (Phe) levels in the mother during pregnancy. Maintenance of blood Phe levels between 120 and 360 μmol/L reduces risks of birth defects. Sapropterin dihydrochloride helps maintain blood Phe control, but there is limited evidence on its risk–benefit ratio when used during pregnancy. Data from the maternal sub-registries—KAMPER (NCT01016392) and PKUDOS (NCT00778206; PKU-MOMs sub-registry)—were collected to assess the long-term safety and efficacy of sapropterin in pregnant women in a real-life setting. Pregnancy and infant outcomes, and the safety of sapropterin were assessed. Final data from 79 pregnancies in 57 women with PKU are reported. Sapropterin dose was fairly constant before and during pregnancy, with blood Phe levels maintained in the recommended target range during the majority (82%) of pregnancies. Most pregnancies were carried to term, and the majority of liveborn infants were reported as ‘normal’ at birth. Few adverse and serious adverse events were considered related to sapropterin, with these occurring in participants with high blood Phe levels. This report represents the largest population of pregnant women with PKU exposed to sapropterin. Results demonstrate that exposure to sapropterin during pregnancy was well-tolerated and facilitated maintenance of blood Phe levels within the target range, resulting in normal delivery. This critical real-world data may facilitate physicians and patients to make informed treatment decisions about using sapropterin in pregnant women with PKU and in women of childbearing age with PKU who are responsive to sapropterin.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.12724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021907","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":"Longitudinal volumetric analysis of gray matter atrophy in metachromatic leukodystrophy","authors":"Murtadha L. Al-Saady,&nbsp;Hristina Galabova,&nbsp;Daphne H. Schoenmakers,&nbsp;Shanice Beerepoot,&nbsp;Caroline Lindemans,&nbsp;Peter M. van Hasselt,&nbsp;Marjo S. van der Knaap,&nbsp;Nicole I. Wolf,&nbsp;Petra J. W. Pouwels","doi":"10.1002/jimd.12725","DOIUrl":"10.1002/jimd.12725","url":null,"abstract":"<p>Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disorder characterized by arylsulfatase A (ASA) deficiency, leading to sulfatide accumulation and myelin degeneration in the central nervous system. While primarily considered a white matter (WM) disease, gray matter (GM) is also affected in MLD, and hematopoietic stem cell transplantation (HSCT) may have limited effect on GM atrophy. We cross-sectionally and longitudinally studied GM volumes using volumetric MRI in a cohort of 36 (late-infantile, juvenile and adult type) MLD patients containing untreated and HSCT treated subjects. Cerebrum, cortical GM, (total) CSF, cerebellum, deep gray matter (DGM) (excluding thalamus) and thalamus volumes were analyzed. Longitudinal correlations with measures of cognitive and motor functioning were assessed. Cross-sectionally, juvenile and adult type patients (infantiles excluded based on limited numbers) were compared with controls at earliest scan, before possible treatment. Patients had lower cerebrum, cortical GM, DGM and thalamus volumes. Differences were most pronounced for adult type patients. Longitudinal analyses showed substantial and progressive atrophy of all regions and increase of CSF in untreated patients. Similar, albeit less pronounced, effects were seen in treated patients for cerebrum, cortical GM, CSF and thalamus volumes. Deterioration in motor performance (all patients) was related to atrophy, and increase of CSF, in all regions. Cognitive functioning (data available for treated patients) was related to cerebral, cortical GM and thalamus atrophy; and to CSF increase. Our findings illustrate the importance of recognizing GM pathology as a potentially substantial, clinically relevant part of MLD, apparently less amenable to treatment.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.12725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012741","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":"Nucleotide metabolism, leukodystrophies, and CNS pathology","authors":"Francesco Gavazzi,&nbsp;Carlos Dominguez Gonzalez,&nbsp;Kaley Arnold,&nbsp;Meghan Swantkowski,&nbsp;Lauren Charlton,&nbsp;Nicholson Modesti,&nbsp;Asif A. Dar,&nbsp;Adeline Vanderver,&nbsp;Mariko Bennett,&nbsp;Laura A. Adang","doi":"10.1002/jimd.12721","DOIUrl":"10.1002/jimd.12721","url":null,"abstract":"<p>The balance between a protective and a destructive immune response can be precarious, as exemplified by inborn errors in nucleotide metabolism. This class of inherited disorders, which mimics infection, can result in systemic injury and severe neurologic outcomes. The most common of these disorders is Aicardi Goutières syndrome (AGS). AGS results in a phenotype similar to “TORCH” infections (<i>Toxoplasma gondii</i>, Other [Zika virus (ZIKV), human immunodeficiency virus (HIV)], Rubella virus, human Cytomegalovirus [HCMV], and Herpesviruses), but with sustained inflammation and ongoing potential for complications. AGS was first described in the early 1980s as familial clusters of “TORCH” infections, with severe neurology impairment, microcephaly, and basal ganglia calcifications (Aicardi &amp; Goutières, <i>Ann Neurol</i>, 1984;15:49–54) and was associated with chronic cerebrospinal fluid (CSF) lymphocytosis and elevated type I interferon levels (Goutières et al., <i>Ann Neurol</i>, 1998;44:900–907). Since its first description, the clinical spectrum of AGS has dramatically expanded from the initial cohorts of children with severe impairment to including individuals with average intelligence and mild spastic paraparesis. This broad spectrum of potential clinical manifestations can result in a delayed diagnosis, which families cite as a major stressor. Additionally, a timely diagnosis is increasingly critical with emerging therapies targeting the interferon signaling pathway. Despite the many gains in understanding about AGS, there are still many gaps in our understanding of the cell-type drivers of pathology and characterization of modifying variables that influence clinical outcomes and achievement of timely diagnosis.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990304","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":"From skin lesions to tyrosinemia type II diagnosis","authors":"Inês S. F. da Silva,&nbsp;Inês Sopa,&nbsp;Daniel Gomes,&nbsp;Lígia Peixoto,&nbsp;Anabela Oliveira","doi":"10.1002/jimd.12720","DOIUrl":"10.1002/jimd.12720","url":null,"abstract":"","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972157","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":"A phenylalanine-free recombinant nutritional protein for the dietary management of phenylketonuria","authors":"Yvonne Mücke,&nbsp;Natalia Jablonka,&nbsp;Nicole Rimann,&nbsp;Hiu Man Grisch-Chan,&nbsp;Bernhard Hoffmann,&nbsp;Stefan Schillberg,&nbsp;Beat Thöny,&nbsp;Stefan Rasche","doi":"10.1002/jimd.12719","DOIUrl":"10.1002/jimd.12719","url":null,"abstract":"<p>Phenylketonuria (PKU) is a congenital metabolic disorder that causes the systemic elevation of phenylalanine (Phe), which is neurotoxic and teratogenic. PKU is currently incurable, and management involves lifelong adherence to an unpalatable protein-restricted diet based on Phe-free amino acid mixtures. Seeking a palatable dietary alternative, we identified a <i>Bacillus subtilis</i> protein (GSP16O) with a well-balanced but low-Phe amino acid profile. We optimized the sequence and expressed a modified Phe-free version (GSP105) in <i>Pseudomonas fluorescens</i>, achieving yields of 20 g/L. The purified GSP105 protein has a neutral taste and smell, is highly soluble, and remains stable up to 80°C. Homozygous <i>enu2</i> mice, a model of human PKU, were fed with diets containing either GSP105 or normal protein. The GSP105 diet led to normalization of blood Phe levels and brain monoamine neurotransmitter metabolites, and prevented maternal PKU. The GSP105 diet thus provides an alternative and efficacious dietary management strategy for PKU.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.12719","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931492","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":"Impact of citrulline substitution on clinical outcome after liver transplantation in carbamoyl phosphate synthetase 1 and ornithine transcarbamylase deficiency","authors":"Denise Aldrian,&nbsp;Birgit Waldner,&nbsp;Georg F. Vogel,&nbsp;Areeg H. El-Gharbawy,&nbsp;Patrick McKiernan,&nbsp;Jerard Vockley,&nbsp;Yuval E. Landau,&nbsp;Fuad Al Mutairi,&nbsp;Karolina M. Stepien,&nbsp;Anne Mei-Kwun Kwok,&nbsp;Yılmaz Yıldız,&nbsp;Tomas Honzik,&nbsp;Silvie Kelifova,&nbsp;Carolyn Ellaway,&nbsp;Allan M. Lund,&nbsp;Mari Mori,&nbsp;Sarah C. Grünert,&nbsp;Sabine Scholl-Bürgi,&nbsp;Thomas Zöggeler,&nbsp;Rupert Oberhuber,&nbsp;Stefan Schneeberger,&nbsp;Thomas Müller,&nbsp;Daniela Karall","doi":"10.1002/jimd.12717","DOIUrl":"10.1002/jimd.12717","url":null,"abstract":"<p>Carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) deficiencies are rare urea cycle disorders, which can lead to life-threatening hyperammonemia. Liver transplantation (LT) provides a cure and offers an alternative to medical treatment and life-long dietary restrictions with permanent impending risk of hyperammonemia. Nevertheless, in most patients, metabolic aberrations persist after LT, especially low plasma citrulline levels, with questionable clinical impact. So far, little is known about these alterations and there is no consensus, whether <span>l</span>-citrulline substitution after LT improves patients' symptoms and outcomes. In this multicentre, retrospective, observational study of 24 patients who underwent LT for CPS1 (<i>n</i> = 11) or OTC (<i>n</i> = 13) deficiency, 25% did not receive <span>l</span>-citrulline or arginine substitution. Correlation analysis revealed no correlation between substitution dosage and citrulline levels (CPS1, <i>p</i> = 0.8 and OTC, <i>p</i> = 1). Arginine levels after liver transplantation were normal after LT independent of citrulline substitution. Native liver survival had no impact on mental impairment (<i>p</i> = 0.67). Regression analysis showed no correlation between <span>l</span>-citrulline substitution and failure to thrive (<i>p</i> = 0.611) or neurological outcome (<i>p</i> = 0.701). Peak ammonia had a significant effect on mental impairment (<i>p</i> = 0.017). Peak plasma ammonia levels correlate with mental impairment after LT in CPS1 and OTC deficiency. Growth and intellectual impairment after LT are not significantly associated with <span>l</span>-citrulline substitution.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.12717","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905833","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":"Plasma lipidomics analysis reveals altered profile of triglycerides and phospholipids in children with Medium-Chain Acyl-CoA dehydrogenase deficiency","authors":"Inês M. S. Guerra,&nbsp;Helena B. Ferreira,&nbsp;Tatiana Maurício,&nbsp;Marisa Pinho,&nbsp;Luísa Diogo,&nbsp;Sónia Moreira,&nbsp;Laura Goracci,&nbsp;Stefano Bonciarelli,&nbsp;Tânia Melo,&nbsp;Pedro Domingues,&nbsp;M. Rosário Domingues,&nbsp;Ana S. P. Moreira","doi":"10.1002/jimd.12718","DOIUrl":"10.1002/jimd.12718","url":null,"abstract":"<p>Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most prevalent mitochondrial fatty acid β-oxidation disorder. In this study, we assessed the variability of the lipid profile in MCADD by analysing plasma samples obtained from 25 children with metabolically controlled MCADD (following a normal diet with frequent feeding and under <span>l</span>-carnitine supplementation) and 21 paediatric control subjects (CT). Gas chromatography–mass spectrometry was employed for the analysis of esterified fatty acids, while high-resolution C18-liquid chromatography-mass spectrometry was used to analyse lipid species. We identified a total of 251 lipid species belonging to 15 distinct lipid classes. Principal component analysis revealed a clear distinction between the MCADD and CT groups. Univariate analysis demonstrated that 126 lipid species exhibited significant differences between the two groups. The lipid species that displayed the most pronounced variations included triacylglycerols and phosphatidylcholines containing saturated and monounsaturated fatty acids, specifically C14:0 and C16:0, which were found to be more abundant in MCADD. The observed changes in the plasma lipidome of children with non-decompensated MCADD suggest an underlying alteration in lipid metabolism. Therefore, longitudinal monitoring and further in-depth investigations are warranted to better understand whether such alterations are specific to MCADD children and their potential long-term impacts.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735444","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":"Fatal cervical myelopathy in a child with glutaric aciduria type 1","authors":"Eline Chauvet,&nbsp;Diana Ribeiro,&nbsp;Ilse Kern,&nbsp;Joel Fluss","doi":"10.1002/jimd.12716","DOIUrl":"10.1002/jimd.12716","url":null,"abstract":"<p>We report the case of a Syrian female refugee with late diagnosis of glutaric aciduria type 1 characterised by massive axial hypotonia and quadriplegia who only started adequate diet upon arrival in Switzerland at the age of 4 years, after a strenuous migration journey. Soon after arrival, she died from an unexpected severe upper cervical myelopathy, heralded by acute respiratory distress after a viral infection. This was likely due to repeated strains on her hypotonic neck and precipitated by an orthotopic os odontoideum who led to atlanto-axial subluxation. This case reminds us not to omit handling patients with insufficient postural control and hypotonia with great care to avoid progressive cervical myelopathy.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.12716","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702666","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 effect of intrathecal recombinant arylsulfatase A therapy on structural brain magnetic resonance imaging in children with metachromatic leukodystrophy","authors":"Samuel Groeschel,&nbsp;Shanice Beerepoot,&nbsp;Lucas Bastian Amedick,&nbsp;Ingeborg Krӓgeloh-Mann,&nbsp;Jing Li,&nbsp;David A. H. Whiteman,&nbsp;Nicole I. Wolf,&nbsp;John D. Port","doi":"10.1002/jimd.12706","DOIUrl":"10.1002/jimd.12706","url":null,"abstract":"<p>This study aimed to evaluate the effect of intrathecal (IT) recombinant human arylsulfatase A (rhASA) on magnetic resonance imaging (MRI)-assessed brain tissue changes in children with metachromatic leukodystrophy (MLD). In total, 510 MRI scans were collected from 12 intravenous (IV) rhASA-treated children with MLD, 24 IT rhASA-treated children with MLD, 32 children with untreated MLD, and 156 normally developing children. Linear mixed models were fitted to analyze the time courses of gray matter (GM) volume and fractional anisotropy (FA) in the posterior limb of the internal capsule. Time courses for demyelination load and FA in the centrum semiovale were visualized using locally estimated scatterplot smoothing regression curves. All assessed imaging parameters demonstrated structural evidence of neurological deterioration in children with MLD. GM volume was significantly lower at follow-up (median duration, 104 weeks) in IV rhASA-treated versus IT rhASA-treated children. GM volume decline over time was steeper in children receiving low-dose (10 or 30 mg) versus high-dose (100 mg) IT rhASA. Similar effects were observed for demyelination. FA in the posterior limb of the internal capsule showed a higher trend over time in IT rhASA-treated versus children with untreated MLD, but FA parameters were not different between children receiving the low doses versus those receiving the high dose. GM volume in IT rhASA-treated children showed a strong positive correlation with 88-item Gross Motor Function Measure score over time. In some children with MLD, IT administration of high-dose rhASA may delay neurological deterioration (assessed using MRI), offering potential therapeutic benefit.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.12706","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697689","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":"Disorders of vesicular trafficking presenting with recurrent acute liver failure: NBAS, RINT1, and SCYL1 deficiency.","authors":"Bianca Peters, Tal Dattner, Lea D Schlieben, Tian Sun, Christian Staufner, Dominic Lenz","doi":"10.1002/jimd.12707","DOIUrl":"https://doi.org/10.1002/jimd.12707","url":null,"abstract":"<p><p>Among genetic disorders of vesicular trafficking, there are three causing recurrent acute liver failure (RALF): NBAS, RINT1, and SCYL1-associated disease. These three disorders are characterized by liver crises triggered by febrile infections and account for a relevant proportion of RALF causes. While the frequency and severity of liver crises in NBAS and RINT1-associated disease decrease with age, patients with SCYL1 variants present with a progressive, cholestatic course. In all three diseases, there is a multisystemic, partially overlapping phenotype with variable expression, including liver, skeletal, and nervous systems, all organ systems with high secretory activity. There are no specific biomarkers for these diseases, and whole exome sequencing should be performed in patients with RALF of unknown etiology. NBAS, SCYL1, and RINT1 are involved in antegrade and retrograde vesicular trafficking. Pathomechanisms remain unclarified, but there is evidence of a decrease in concentration and stability of the protein primarily affected by the respective gene defect and its interaction partners, potentially causing impairment of vesicular transport. The impairment of protein secretion by compromised antegrade transport provides a possible explanation for different organ manifestations such as bone alteration due to lack of collagens or diabetes mellitus when insulin secretion is affected. Dysfunction of retrograde transport impairs membrane recycling and autophagy. The impairment of vesicular trafficking results in increased endoplasmic reticulum stress, which, in hepatocytes, can progress to hepatocytolysis. While there is no curative therapy, an early and consequent implementation of an emergency protocol seems crucial for optimal therapeutic management.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567139","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}