Molecular Genetics and Metabolism Reports最新文献

{"title":"Case report of neuronopathic mucopolysaccharidosis type II: Early intracerebroventricular enzyme replacement therapy and hematopoietic cell transplantation with developmental outcomes up to 5 years of age","authors":"Azuma Ikari ,&nbsp;Asahito Hama ,&nbsp;Torayuki Okuyama","doi":"10.1016/j.ymgmr.2025.101254","DOIUrl":"10.1016/j.ymgmr.2025.101254","url":null,"abstract":"<div><div>Neuronopathic mucopolysaccharidosis type II (MPS II) is a severe lysosomal storage disorder associated with early-onset developmental regression and a poor prognosis. Although enzyme replacement therapy (ERT) and hematopoietic cell transplantation (HCT) have been employed to address systemic symptoms, they have not demonstrated sufficient efficacy in treating central nervous system (CNS) involvement. The intracerebroventricular administration of idursulfase beta has emerged as a novel approach for targeting CNS manifestations. Here, we report the clinical course of a male patient diagnosed with neuronopathic MPS II at 2 months of age, based on family history and genetic analysis. Intravenous ERT was initiated early, followed by the introduction of intracerebroventricular idursulfase beta at 10 months, and HCT at 23 months. Since then, only intracerebroventricular ERT has been continued. At 5 years of age, the patient exhibited age-appropriate neurodevelopment, stable cognitive function, and normal physical growth without signs of developmental regression. Imaging findings remained stable, and cerebrospinal fluid biomarkers normalized. Notably, the patient harbored a missense variant potentially associated with residual enzymatic activity, which may have contributed to favorable outcomes. To our knowledge, this is the first reported case in which normal development was maintained until 5 years of age in a patient with neuronopathic MPS II. This case highlights the potential benefits of early diagnosis and a multimodal therapeutic strategy, including intracerebroventricular ERT and HCT, for preserving neurodevelopment. It also holds significance as a rare but valuable example, suggesting the efficacy of a novel treatment paradigm for a condition traditionally associated with a poor prognosis.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101254"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic signatures in Gaucher disease subtypes: A systems biology perspective","authors":"Mohammad Elahimanesh ,&nbsp;Reza Ganjali ,&nbsp;Mohammad Najafi","doi":"10.1016/j.ymgmr.2025.101274","DOIUrl":"10.1016/j.ymgmr.2025.101274","url":null,"abstract":"<div><div>Gaucher disease (GD) is a lysosomal storage disorder caused by the failure of <em>GBA1</em> (Glucosylceramidase Beta 1). The aim of study was to analyze and enrich signaling pathways with transcriptomic profiles in cultured skin fibroblasts of GD subtypes (GD1, GD2, GD3) using GEO datasets. Differentially expressed genes (DEGs) were identified using the Limma package in R with a significance threshold (adjusted <em>p</em>-value &lt;0.05 and |log2FC| &gt; 1) and were used in gene networks constructed by Cytoscape. In GD1, up regulated genes (<em>TP53</em>, <em>COL4A1</em>) were found in mRNA splicing and ECM organization, while down regulated genes (<em>IL6</em>, <em>TGFBR2</em>) were linked to cytokine and TGF-β signaling pathways. GD2 showed upregulation of <em>MMP1</em>, <em>CXCL8</em>, and interferon-related genes (<em>ISG15</em>, <em>MX1</em>), associated with interleukin-4/13 signaling and ECM dysregulation, reflecting severe neuroinflammation. GD3 exhibited upregulation of <em>FOS</em>, <em>AKT1</em> (&gt;5 years), and <em>POSTN</em>, <em>EGR2</em> (&lt;5 years), found in PI3K/AKT and myelination signaling pathways, alongside down regulated <em>CXCL8</em> and <em>PTGS2</em> linked to receptor tyrosine kinase signaling pathway. Gene networks identified hub genes (<em>PSAP</em>, <em>CTSB</em> for GD1; <em>LAMP2</em>, <em>GAA</em> for GD2/GD3) and enriched pathways (glycosphingolipid metabolism, lysosomal function). Top 5 % DEGs, including KDM5D (GD1), MMP1 (GD2), and FOSB (GD3), were proposed as subtype-specific markers. The findings highlighted distinct molecular signatures between GD1 (immune/ECM-focused) and GD2/GD3 (neuroinflammatory/neurodevelopmental), informing targeted diagnostics.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101274"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and biochemical characterization of a patient with prolidase deficiency, a rare disorder of collagen metabolism","authors":"Troy K. Coody ,&nbsp;Irene De Biase ,&nbsp;Julie M. Porter ,&nbsp;Marzia Pasquali ,&nbsp;Brian J. Shayota","doi":"10.1016/j.ymgmr.2025.101258","DOIUrl":"10.1016/j.ymgmr.2025.101258","url":null,"abstract":"<div><div>Prolidase deficiency (PD) is an autosomal recessive inborn error of metabolism, with an estimated incidence of 1 per 1.25 million births. Prolidase is critical for the turnover of proline and hydroxyproline-rich proteins, such as collagen. Collagen metabolism is essential for matrix regeneration during cellular proliferation and complex bodily functions such as wound healing and immunological cell differentiation. PD clinical manifestations include persistent skin ulcerations and poor wound healing, hypertelorism, high arched palate, depressed nasal bridge, micrognathia, splenomegaly, intellectual disability, recurring infections, and hematological abnormalities. Biochemically, a diagnosis of PD is supported by increased urinary excretion of glycyl-proline and other proline-containing iminopeptides detected by amino acid analysis. There are no current targeted therapies, but suggested interventions have included topical proline-glycine ointment, manganese supplementation, topical and oral steroids, and immunomodulation with monoclonal antibodies.</div><div>Here, we describe a 30-year-old patient with PD whose clinical course has been characterized by recurrent skin ulcerations/cysts with secondary scarring, recurrent infections, anemia, thrombocytopenia, lymphopenia, elevated liver enzymes, hirsutism, and seemingly unrelated papillary thyroid cancer. Skin manifestations were particularly severe due to the added complication of a diagnosis of hidradenitis suppurativa. Quantitative analysis of amino acids and related compounds revealed markedly elevated glycyl-proline in urine and plasma. To further characterize the biochemical phenotype, untargeted metabolomic analysis was sent on both plasma and urine. An increase was noted in several metabolites from the prolidase-dependent dipeptide recycling pathways. A better understanding of the pathophysiological mechanisms involved in prolidase deficiency may prove useful as different therapeutic approaches are being considered.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101258"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical and clinical response to a sulfur-restricted diet in ethylmalonic encephalopathy","authors":"Steven H. Lang ,&nbsp;Andres Caceres Salgado ,&nbsp;Matthew T. Snyder ,&nbsp;Brandy Rawls-Castillo ,&nbsp;Aaron Williams ,&nbsp;Charul Gijavanekar ,&nbsp;Sarah H. Elsea ,&nbsp;Xia Wang ,&nbsp;Mary Elizabeth M. Tessier ,&nbsp;Claudia Soler-Alfonso ,&nbsp;Fernando Scaglia","doi":"10.1016/j.ymgmr.2025.101270","DOIUrl":"10.1016/j.ymgmr.2025.101270","url":null,"abstract":"<div><h3>Introduction</h3><div>Ethylmalonic encephalopathy (EE) is an often-severe inborn error of metabolism caused by biallelic variants in the <em>ETHE1</em> gene leading to impaired detoxification of hydrogen sulfide (H₂S). H₂S is produced both exogenously by anerobic intestinal bacteria as well as by the endogenous catabolism of the sulfur-containing amino acids methionine and cysteine. Existing therapies including metronidazole, <em>N</em>-acetylcysteine (NAC), and orthotopic liver transplantation (OLT) have been pursued with the objective of reducing or detoxifying exogenously produced H₂S. However, strategies to reduce endogenously produced H₂S using a methionine and cysteine restricted diet are an understudied therapeutic avenue.</div></div><div><h3>Methods</h3><div>We performed an open-label, single-arm study to evaluate the effects of dietary intervention with a methionine and cysteine restricted diet (20–30 mg/kg/day) on biochemical parameters and overall clinical trajectory in three patients with molecularly confirmed ethylmalonic encephalopathy (two with attenuated phenotypes, one classically affected). All three patients were receiving a combination of medical therapy with metronidazole and NAC and were status-post OLT at the time of diet initiation. Plasma butyrylcarnitine (C4) levels were measured at diagnosis, serially following initiation of medical therapy and OLT, and at regular follow-up visits in a metabolic clinic after diet initiation. Additionally, we obtained untargeted metabolomics studies and directly evaluated ethylmalonate, butyrylcarnitine, isobutyrylcarnitine, isovalerylcarnitine, 2-methylbutyrylcarnitine, glutarylcarnitine, and methylsuccinate levels in the pre- OLT/medical therapy, post- OLT/medical therapy, and post- sulfur-restricted diet states.</div></div><div><h3>Results</h3><div>We observed a 20–38 % reduction in plasma C4 levels in all three patients following OLT and combination medical therapy with NAC and metronidazole. An 8–10 % reduction in C4 was observed following the introduction of dietary therapy in the two patients with attenuated phenotypes and an 82 % increase in C4 was seen in the patient with the classical phenotype. The metabolic profile as assessed by untargeted metabolomics analysis was largely unchanged in the pre-OLT/medical therapy, post-OLT/medical therapy, and post-diet states.</div></div><div><h3>Conclusions</h3><div>The modest biochemical response to a sulfur-restricted diet observed in our cohort likely reflects the relatively minor contribution of endogenous sulfur-containing amino acid catabolism to overall H₂S production. Further work is needed to study the impact of dietary intervention on the natural history of EE including diet only trials in the animal model as well as in the pre-OLT period in human participants.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101270"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactic acidosis, rhabdomyolysis, and hyperammonemia: Atypical presentation in a new patient with PDE-ALDH7A1 defect","authors":"Marina Bottino ,&nbsp;Monica Boyer ,&nbsp;Maija R. Steenari ,&nbsp;Rebekah Barrick ,&nbsp;Jose E. Abdenur","doi":"10.1016/j.ymgmr.2025.101260","DOIUrl":"10.1016/j.ymgmr.2025.101260","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Pyridoxine-Dependent Epilepsy (PDE) is an autosomal recessive disorder caused by biallelic variants in ALDH7A1. The most common presentation is intractable seizures in the neonatal/early infantile period, which respond to pyridoxine. Other manifestations include perinatal asphyxia, hypoglycemia, and neuroimaging abnormalities. Despite early treatment, patients often have neurodevelopmental abnormalities. Treatment guidelines recommend triple therapy with pyridoxine, dietary lysine restriction, and arginine supplementation.&lt;/div&gt;&lt;div&gt;We report an individual presenting with laboratory abnormalities suggestive of mitochondrial disease. Born full-term, via NSVD, with normal Apgar scores and cord gases. At 30 min, grunting developed, and at 4 h of life, jerky movements with eye deviation were noted. Laboratory results revealed acidosis (pH 7.15) and increased lactate (11.4 mMol/L, rr &lt;2.1). The patient was started on IV fluids, given 1 mEq/kg of sodium bicarbonate, and transferred for higher-level care. Upon arrival, the evaluation was notable for hypotonia, non-rhythmic jerking movements, rapid eye blinking, and a critically low pH (6.92), high lactate (15.3 mMol/L), hyperammonemia (153 μMol/L, rr &lt; 75), and a creatine kinase level of 15,742 U/L (rr 35–230). A single dose of phenobarbital was given, and the baby was intubated and ventilated. Video electroencephalogram (vEEG) showed a discontinuous background with abnormal, sharply contoured bursts alternating with suppression, with no clinical correlation. The patient was treated with continuous sodium bicarbonate drip and IV fluids, restricting glucose. Abnormal movements, lactic acidosis, and hyperammonemia resolved within 24 h. An electroencephalogram (EEG) at 5 days of life (DOL) showed a mildly discontinuous background with no epileptic activity, and MRI showed a thin corpus callosum, cysts, and cerebellar hypoplasia. Creatine kinase peaked at 30,995 U/L and normalized on DOL 8. Organic acids revealed significant increases in lactate, 2-OH-butyrate, pyruvate, 3-OH-butyrate, 2-OH-isovalerate, and a mild increase in Krebs-cycle intermediates.&lt;/div&gt;&lt;div&gt;Rapid whole genome sequence (rWGS) was available on DOL 9, disclosing two variants in &lt;em&gt;ALDH7A1&lt;/em&gt;: c.1559C &gt; T p.Ser520Phe, previously reported, and c.1540 A &gt; G p.Lys514Glu, considered a VUS. Treatment with pyridoxine started at 30 mg/kg/day. Pre-treatment biomarkers were consistent with the diagnosis of PDE-ALDH7A1: urine Pipecolate 117.8 mMol/mol, RR ≤10, 6-oxo-Pipecolate 8.4 mMol/mol, RR ≤2.0 and plasma alpha-aminoadipic semialdehyde (AASA) 5.2 uMol/L, RR &lt;0.4. Treatment with arginine was added on DOL 10 (200 mg/kg/day) and a lysine-restricted diet on DOL 12, after TPN was discontinued. Clinical exam improved, no seizures were observed, and EEG normalized. PDE biomarkers decreased, and the patient was discharged home on DOL 25.&lt;/div&gt;&lt;div&gt;Elevated lactic acid has been reported in up to 70.3 % of PDE-ALDH7A1 patients ","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101260"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term neuromuscular, cardiac and liver outcomes in an adult man affected with Chanarin-Dorfman syndrome","authors":"Kinza Noman ,&nbsp;Andreas Tridimas ,&nbsp;James B. Lilleker ,&nbsp;Gaetano Nucifora ,&nbsp;Peter Woolfson ,&nbsp;Daniel du Plessis ,&nbsp;Alison Woodall ,&nbsp;Andrew Oldham ,&nbsp;Mark E. Roberts ,&nbsp;John Bassett ,&nbsp;Federico Roncaroli ,&nbsp;Simon A. Jones ,&nbsp;Stefan Coassin ,&nbsp;Florian Kronenberg ,&nbsp;Karolina M. Stepien","doi":"10.1016/j.ymgmr.2025.101265","DOIUrl":"10.1016/j.ymgmr.2025.101265","url":null,"abstract":"<div><div>Chanarin-Dorfman syndrome (CDS) is an ultra-rare autosomal recessive subtype of neutral lipid storage disorder (NLSD); it is characterised by ichthyosis and intracytoplasmic accumulation of lipid droplets containing triglycerides, most commonly in granulocytes, muscle fibres, skin and liver. Several pathogenic variants in the <em>ABHD5</em>/CGI-58 gene have been described. Clinical manifestations include steatohepatitis, myopathy, ophthalmic disease, developmental delay. Liver involvement is an important cause of morbidity and mortality.</div><div>We present a case of a 26-year-old male diagnosed with ichthyotic NLSD in childhood, who developed progressive myopathy and cardiac fibrosis in adulthood. He was treated with a combination of low-fat diet, MCT oil and co-enzyme Q10 which resulted in an initial improvement in muscle strength and stabilisation of muscle symptoms and well-being.</div><div>Synopsis: Medical and dietetic management of liver and muscle complications in Chanarin-Dorfman syndrome.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101265"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Full recovery of vision following early and intensive hemodialysis in an 18-year-old woman with methylmalonic acidemia-related optic neuropathy","authors":"Alicia Guertin ,&nbsp;Raoul Kanav Khanna ,&nbsp;Marine Tardieu ,&nbsp;Maud François ,&nbsp;Hélène Blasco ,&nbsp;Isabelle Benz de Bretagne ,&nbsp;Jean-François Benoist ,&nbsp;Adrien Bigot ,&nbsp;Nathalie Tressel ,&nbsp;François Maillot ,&nbsp;François Labarthe","doi":"10.1016/j.ymgmr.2025.101279","DOIUrl":"10.1016/j.ymgmr.2025.101279","url":null,"abstract":"<div><h3>Background</h3><div>Methylmalonic acidemia (MMA) caused by complete or partial deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase (mut⁰ or mut- enzymatic subtype, respectively) leads to the accumulation of toxic organic acids, causing severe organ dysfunction and life-threatening complications. Despite appropriate treatment, optic neuropathy has been reported as a vision-threatening complication of MMA, often resulting in debilitating sequelae.</div></div><div><h3>Case report</h3><div>We present the case of an 18-year-old woman with isolated mut° MMA and with chronic kidney disease stage 3 who presented with a rapid decline in distance and near visual acuity in both eyes. Goldmann visual field perimetry revealed bilateral central relative scotomas with preserved peripheral vision. Visual evoked potentials were unstructured in both eyes, despite normal retinal imaging, indicating optic neuropathy. Metabolic testing revealed elevated levels of methylmalonic acid in both plasma and urine, and increased lactate levels in the plasma and cerebrospinal fluid. Based on the hypothesis of subacute toxicity from methylmalonic acid metabolites, intensive intermittent hemodialysis was initiated, which rapidly decreased the patient's plasma methylmalonic acid level. We also added an oral supplement of coenzyme Q10 and vitamin E. With this treatment, the patient's vision rapidly recovered, and visual function normalized five months later. No progression of optic neuropathy occurred in the eight years follow up after a combined liver/kidney transplant procedure.</div></div><div><h3>Conclusion</h3><div>Optic neuropathy is a rare long-term complication of isolated MMA, presumably due to the chronic or subacute accumulation of toxic methylmalonic acid metabolites. This case report highlights the importance of early and intensive hemodialysis in achieving favorable visual outcomes by reducing toxic metabolite levels in both blood and central nervous system. In the long-term, liver or combined liver-kidney transplantation should be discussed.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101279"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world experience of switching to taliglucerase among patients with Gaucher disease in Québec: A case series","authors":"Angelo Rizzolo ,&nbsp;Marie-Claude Miron ,&nbsp;Jean-François Delisle ,&nbsp;Nathalie Alos ,&nbsp;Philippe M. Campeau ,&nbsp;François Mercier","doi":"10.1016/j.ymgmr.2025.101257","DOIUrl":"10.1016/j.ymgmr.2025.101257","url":null,"abstract":"<div><div>Enzyme replacement therapy (ERT) for Gaucher disease (GD) effectively prevents skeletal, visceral, and hematologic complications of this inherited, lysosomal storage disorder. Taliglucerase is one of the three commercially available ERT products and became the recommended first-line therapy in Québec, Canada in 2016. Thus, 19 patients were switched from imiglucerase to taliglucerase, but more than a quarter experienced significant side effects. Here, we summarize these patients' clinical course and describe 6 suspected product-related adverse-effects.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101257"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietetic management of adults with Classical Galactosaemia in the UK: A care consensus document","authors":"Louise Robertson ,&nbsp;Simon Tapley ,&nbsp;Alexa Sparks ,&nbsp;Joy McDonald ,&nbsp;Ellen Condie ,&nbsp;Sarah Bailey","doi":"10.1016/j.ymgmr.2025.101277","DOIUrl":"10.1016/j.ymgmr.2025.101277","url":null,"abstract":"<div><div>Classical Galactosaemia is a rare, inherited metabolic disorder requiring lifelong dietary management. Despite increasing numbers of adults living with this condition, there is currently no formalised training or standardised guidance for United Kingdom (UK) dietitians managing adult patients. In response to this gap, a group of experienced UK dietitians specialising in inherited metabolic disorders collaboratively developed the first UK consensus document for the dietetic management of adults with Classical Galactosaemia. The guidance was formulated over a 12-month period through structured virtual meetings, with the objective of promoting consistency in clinical practice, supporting equitable service provision, and enhancing patient outcomes. Key areas addressed include dietary interventions, nutritional adequacy, bone health, dietary management with cognitive impairment, and reproductive health. The document also highlights critical gaps in the evidence base, particularly regarding individual galactose tolerance, the identification of sensitive biomarkers for monitoring, and the potential for dietary liberalisation in adulthood. This consensus guidance serves as a foundational resource for clinical practice and professional development, aiming to improve the quality and consistency of dietetic care for adults with Classical Galactosaemia across the UK.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101277"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreatic involvement in EPG5-related disorders","authors":"Dennis T. Famili ,&nbsp;Gehad Elghazali ,&nbsp;Emanuela Argili ,&nbsp;Russell P. Saneto ,&nbsp;Michael Harris ,&nbsp;Oleg Gerasimenko ,&nbsp;Julia Gerasimenko ,&nbsp;Manolis Fanto ,&nbsp;Hormos Salimi Dafsari ,&nbsp;Heinz Jungbluth","doi":"10.1016/j.ymgmr.2025.101273","DOIUrl":"10.1016/j.ymgmr.2025.101273","url":null,"abstract":"<div><div>Vici syndrome is a severe neurodevelopmental multisystem disorder characterized by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and hypopigmentation. There may be additional variable involvement of other organs. <em>VS</em> is caused by recessive mutations in <em>EPG5</em>, encoding a tethering factor with important roles in autophagy, an essential cellular homeostatic mechanism involved in metabolic adaptation, infection defence and quality control of proteins and organelles.</div><div>Acute pancreatitis is an inflammatory syndrome caused by an acute injury resulting in failure of safeguarding mechanisms preventing autodigestion. Chronic pancreatitis is characterized by replacement of pancreatic parenchyma with fibrotic tissue following repeated injury, resulting in endocrine and exocrine insufficiency. In addition to common causes such as excessive ethanol consumption, gallstones and pharmacological factors, there are likely to be additional genetic contributors.</div><div>Here we report 3 patients with <em>EPG5</em>-related Vici syndrome and not previously recognized pancreatic involvement, ranging from otherwise asymptomatic amylase elevations to acute pancreatitis and pancreatic insufficiency. A topical literature review on the role of autophagy and autophagy-related genes in the pancreas suggested that autophagy defects may affect critical pathological events involved in pancreatitis, in particular abnormal vacuole formation in acinar cells, inappropriate intra-acinar trypsinogen activation, mitochondrial dysfunction and disturbed calcium homeostasis.</div><div>These findings illustrate the importance of <em>EPG5</em> and other autophagy-related genes in normal pancreatic function and expand the phenotypical spectrum of <em>EPG5</em>-related disorders.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101273"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}