JIMD reports最新文献

{"title":"Correction to “Sleep Quality in Children With Hepatic Glycogen Storage Diseases, a Prospective Observational Pilot Study”","authors":"","doi":"10.1002/jmd2.70004","DOIUrl":"https://doi.org/10.1002/jmd2.70004","url":null,"abstract":"<p>L. Agnoletto, M. Vandeleur, M. White, A-M. Adams, R. Halligan, H. Peters, “Sleep Quality in Children With Hepatic Glycogen Storage Diseases, a Prospective Observational Pilot Study,” <i>JIMD Reports</i> 66, no. 1 (2025): e12462, https://doi.org/10.1002/jmd2.12462.</p><p>In the article, there should be a note saying “Rebecca Halligan and Heidi Peters are contributed equally to this work and are co-last authors”.</p><p>We apologize for this error.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-[18F] FDG PET/CT in Rapid Late-Onset Multiple Acyl-CoA Dehydrogenase Deficiency: A Case Report","authors":"Astrid Høj,&nbsp;Sonja Holm-Yildiz,&nbsp;Thomas Krag,&nbsp;Danijela Dejanovic,&nbsp;Thomas van Overeem Hansen,&nbsp;Morten Dunø,&nbsp;Mette Cathrine Ørngreen,&nbsp;John Vissing,&nbsp;Nicoline Løkken","doi":"10.1002/jmd2.12469","DOIUrl":"https://doi.org/10.1002/jmd2.12469","url":null,"abstract":"<p>Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare inborn metabolic myopathy affecting fat and protein metabolism. Patients with late-onset MADD typically present with exercise intolerance and muscle weakness. We present a patient with an acute, very late-onset symptom debut at 52 years of age. Over 5 months, the patient deteriorated from asymptomatic to almost complete loss of ambulation. He had a substantial weight loss, head-drop, progressive proximal limb and chewing weakness. Due to the rapid progression, amyotrophic lateral sclerosis, myositis, myasthenia gravis and a paraneoplastic syndrome in relation to underlying malignancy were considered first. A 2-[¹⁸F] FDG PET/CT scan was performed to exclude a paraneoplastic syndrome. The scan revealed diffuse and symmetric, pathologically high 2-[¹⁸F] FDG-uptake in the patient's neck, shoulder, and paravertebral muscles, which was later suggested as a sign of a metabolic myopathy. Muscle biopsy (Oil Red O staining) and acylcarnitine profile (elevated C5-C18 acylcarnitines) findings suggested MADD, which was confirmed by genetic analysis showing biallelic variants in the <i>ETFDH</i> gene (c.1763A&gt;G, p.(His588Arg); c.897G&gt;A, p.(Leu299=)). After 1 month of dietary intervention and daily diet supplements (riboflavin 400 mg TID, levocarnitine 1 g TID, Q10 150 mg qD in two doses), the patient had almost recovered to his habitual level. A posttreatment muscle biopsy showed less disrupted ultrastructure of the myofibers. We learned from this case of rapid and late-onset MADD that 2-[¹⁸F] FDG PET/CT, with diffuse and symmetric 2-[¹⁸F] FDG-uptake in skeletal muscle, can be valuable in clarifying this rare diagnosis.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.12469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Expanding the Genetic and Clinical Spectrum of SLC25A42 Associated Disorders and Testing of Pantothenic Acid to Improve CoA Level In Vitro”","authors":"","doi":"10.1002/jmd2.70002","DOIUrl":"https://doi.org/10.1002/jmd2.70002","url":null,"abstract":"<p>\u0000 <span>K. Heckmann</span>, <span>A. Iuso</span>, <span>J. Reunert</span> et al., “ <span>Expanding the Genetic and Clinical Spectrum of SLC25A42-Associated Disorders and Testing of Pantothenic Acid to Improve CoA Level In Vitro</span>,” <i>JIMD Reports</i> <span>65</span> (<span>2024</span>): <span>417</span>–<span>425</span>, https://doi.org/10.1002/jmd2.12441.\u0000 </p><p>Affiliation of Eleonora Paradies was listed incorrectly. Correct affiliation is:</p><p>Katharina Heckmann¹, Arcangela Iuso^2,3, Janine Reunert¹, Marianne Grüneberg¹, Anja Seelhöfer¹, Stephan Rust¹, Giuseppe Fiermonte⁴, Eleonora Paradies⁵, Carmela Piazzolla⁴, Manoj Mannil⁶, Thorsten Marquardt¹.</p><p>¹ Department of General Pediatrics, University Hospital, Münster, Germany.</p><p>² Institute of Neurogenomics, Helmholtz Zentrum München, Neuherberg, Germany.</p><p>³ Institute of Human Genetics, Technical University of Munich, Germany.</p><p>⁴ Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Italy.</p><p>⁵ National Research Council, Institute of Biomembranes, Bioenergetics and Molecular Biotechnology (IBIOM), Bari, Italy.</p><p>⁶ Clinic of Radiology, University Hospital Münster, Münster, Germany.</p><p>We apologize for this error.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective Study of Clinical and Genetic Profiles of Alpha-Mannosidosis Patients From the UAE","authors":"Ali K. Saad,&nbsp;Tasneem Al-Hammadi,&nbsp;Shaikha Al-Ameri,&nbsp;Aisha Al-Shamsi,&nbsp;Noura Al-Dhaheri,&nbsp;Amal Al Tenaiji,&nbsp;Fatma Al Jasmi","doi":"10.1002/jmd2.70001","DOIUrl":"https://doi.org/10.1002/jmd2.70001","url":null,"abstract":"<p>Alpha-mannosidosis (AM; OMIM 248500) is a rare autosomal recessive lysosomal storage disorder caused by mutations in <i>MAN2B1</i>, which codes for the lysosomal alpha-mannosidase enzyme (LAMAN; EC:3.2.1.24). Clinical characteristics include developmental delay, hearing impairment, and recurrent infections. A retrospective analysis of nine case series of patients with AM (23 months–42 years) from six consanguineous families in the United Arab Emirates (UAE) was conducted. In two Emirati families, homozygous nonsense mutations were present: c.2368C&gt; T, p.(Gln790*) and c.2119C&gt; T, p.(Gln707*). Further, in the Emirati and Syrian families two splicing variants c.2356-2A&gt;G and c.1929-2A&gt;G were present, respectively. All patients had infantile-onset and common clinical features, including coarse facies, developmental delays, hearing loss, and recurrent infections. Macrocephaly was observed in all patients with documented head circumference, except one microcephalic patient who had a dual genetic diagnosis. Hepatosplenomegaly and autoimmune diseases were reported in one and three patients, respectively. Additionally, psychiatric manifestations were noted in two adult patients. The mean age of diagnosis was 14 years for adults (&gt; 16 years) and 2 years for pediatric patients (&lt; 16 years). Significant diagnostic delay comparing older and younger generations is likely due to the increasing awareness of genetic disorders and the availability of genetic testing. In terms of treatment, enzyme replacement therapy (ERT) was administered to two patients, alleviating recurrent infections. Two patients underwent hematopoietic stem cell transplantation (HSCT), whereas one patient underwent combined ERT and HSCT. This retrospective analysis identified different truncating mutations associated with early-onset AM. The clinical presentations of these mutations range from attenuated to moderate. Our analysis clearly highlights the high birth prevalence of AM in the UAE, indicating the need for awareness and genetic counseling for prevention.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver transplantation in glycogen storage disease type III: A case-series","authors":"Simon Gay,&nbsp;Adrien Bigot,&nbsp;Louis d'Alteroche,&nbsp;Fanny Dujardin,&nbsp;Gaëlle Fromont-Hankard,&nbsp;Nathalie Tressel,&nbsp;Ephrem Salame,&nbsp;François Maillot","doi":"10.1002/jmd2.12463","DOIUrl":"10.1002/jmd2.12463","url":null,"abstract":"<p>Glycogen storage disease type III (GSD III) is a rare metabolic disorder characterized by a deficiency of liver and muscle amylo-1,6-glucosidase. This condition presents with severe hepatic symptoms in childhood, mostly hepatomegaly, hypoglycemia in half of patients, while muscular complications may predominate in adulthood. Hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC) are common complications in older patients. Therefore, regular monitoring, including HCC screening, is essential for effective disease management. In some severe cases, liver transplantation (LT) may be necessary to treat life-threatening complications. Here, we report the cases of three adult patients who required LT during the course of GSD III. Case #1: Diagnosis of GSD III was made in childhood, with development of hepatocellular carcinoma requiring partial hepatectomy followed by LT due to post-operative complications. The patient recovered well and had favorable surveillance over a seven-year period. Case #2: Diagnosis of GSD III in early childhood, with progression to cirrhosis in adulthood. Severe hepatic encephalopathy necessitated urgent transplantation, with a favorable recovery, although muscular symptoms remained present. Case #3: Diagnosis of GSD III in childhood, followed by later development of hepatocellular adenocarcinoma requiring LT. The patient recovered well and did not exhibit post-transplant muscular symptoms. Post-LT outcome was positive for all three GSD III patients, with significant improvement in liver function and no complications related to immunosuppression. Long-term hepatic monitoring is essential for early detection of complications such as cirrhosis and HCC. LT indications should be individually evaluated, preferring less invasive options. These cases highlight the importance of a multidisciplinary approach to the effective management of GSD III, with particular attention to hepatic and muscular surveillance.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotypic Spectrum in a Cohort of Sri Lankan Patients With Homocystinuria","authors":"Hewa Warawitage Dilanthi,&nbsp;Kandana Liyanage Subhashinie Jayasena,&nbsp;Nambage Dona Priyani Dhammika,&nbsp;Neluwa Liyanage Ruwan Indika,&nbsp;Matara Mahavidanage Nishani De Silva,&nbsp;Imalke Kankananarachchi,&nbsp;Pushpa Malkanthi Gardiye Punchihewa,&nbsp;Dharma Irugalbandara,&nbsp;Sabine Schroeder,&nbsp;Kosala Karunaratne,&nbsp;Eresha Jasinge","doi":"10.1002/jmd2.12470","DOIUrl":"10.1002/jmd2.12470","url":null,"abstract":"<p>Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is a rare metabolic disorder inherited as an autosomal recessive trait. Spectrum of genetic variants in <i>CBS</i> gene and their correlation with the phenotypes of homocystinuria in Sri Lankan patients have not been reported to date. The objective of this study was to identify the genotypes and genotype–phenotype correlations in a cohort of Sri Lankan patients with homocystinuria due to CBS deficiency. We determined the variants in <i>CBS</i> gene in 14 Sri Lankan patients with homocystinuria, from 9 unrelated families. The clinical features and the biochemical response to pyridoxine were studied for further correlations. Among the 14 patients, the common clinical features were ectopia lentis (100%), intellectual disability (92%) and marfanoid features (78%) at presentation while three of them had developed osteoporosis (21%). Median age at diagnosis was 8 years (range 2–12). Three pathogenic variants (c.1006C&gt;T, c.785C&gt;T and c.19del) and two likely pathogenic variants (c.869C&gt;T, c.772G&gt;A) in <i>CBS</i> gene were identified. Thirteen patients with homozygous genotypes were non-responsive to pyridoxine while the only patient with the compound heterozygous genotype (c.869C&gt;T/c.772G&gt;A) responded to pyridoxine treatment. The genotypic spectrum observed in Sri Lankan patients is unique and mostly associated with pyridoxine non-responsiveness. The majority of the patients were identified clinically at a later stage of the disease due to lack of a screening programme in the country. Therefore, it is important to improve the awareness of the disease among the clinicians in the interest of early diagnosis and early commencement of metabolic treatment.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Single-Center Retrospective Cohort Study of Biopterin Metabolism Disorders in the United Arab Emirates","authors":"Omar Jarrah,&nbsp;Mahmood Nouri,&nbsp;Aisha Al Shamsi","doi":"10.1002/jmd2.12468","DOIUrl":"10.1002/jmd2.12468","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tetrahydrobiopterin (BH4) deficiencies comprise a group of five neurometabolic disorders caused by five genetic defects responsible for BH4 biosynthesis and regeneration. Their global prevalence remains unknown, and variance exists among different countries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To describe clinical, biochemical, molecular genetic data and follow-up of patients with BH4 deficiency seen in Tawam Hospital.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective study of all patients with BH4 disorders who were followed up between January 2010 and December 2023 in Tawam Hospital. All data were retrieved from patients' electronic charts, including baseline characteristics, developmental milestones, family history, and clinical examination. Radiological and laboratory investigations, including phenylalanine levels, prolactin levels, CSF study, urine and plasma pterin profiles, and molecular tests, were reviewed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ten patients with BH4 deficiencies were found. The youngest patient was diagnosed at 3- weeks, and the oldest was nine; 70% were male, consanguineous 80%, and 40% were Emirati. Prematurity was reported in two patients. Intrauterine growth restriction was found in 70%, and microcephaly in 40%. Eighty percent had developmental delay, and 2 patients had behavioral issues. Seizure and movement disorders were reported in five and three patients, respectively. Brain MRI showed cortical atrophic changes, corpus callosum hypoplasia, hyperintensities in the parieto-occipital region, and periventricular white matter. Abnormal Newborn screening was found in 60%, with initial high phenylalanine levels (&gt;120 μmol/L) in 80%. Prolactin level was high in all studied patients. Four patients' cerebrospinal fluid neurotransmitter metabolites were evaluated. Blood for DHPR screening and urine pterin profile were done on eight patients. Nine patients had molecular testing. DHPR deficiency was most commonly reported among studied patients (50%), with five novel variants in the <i>QDPR</i> gene. The second prevalent disorder was PTPS deficiency and only one patient with SR deficiency.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This cohort offers an in-depth clinical and genetic understanding of BH4 deficiencies from a single center in the UAE. It describes new genetic variants and addresses diagnostic challenges to enhance the patient's diagnosis ","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D,L-3-hydroxybutyrate in the treatment of glucose transporter 1 deficiency syndrome (Glut1DS)","authors":"Aya Amer,&nbsp;Kathryn Murrell,&nbsp;Liza Edmonds,&nbsp;Isaac Bernhardt,&nbsp;Rhonda Akroyd,&nbsp;Bryony Ryder,&nbsp;Callum Wilson,&nbsp;Emma Glamuzina","doi":"10.1002/jmd2.12461","DOIUrl":"10.1002/jmd2.12461","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Deficiency of the Glut1 transporter due to mono-allelic variants in <i>SLC2A1</i> causes hypoglycorrhachia, resulting in a neurological spectrum from neonatal epilepsy to adult-onset paroxysmal movement disorders (PMD). The brain utilises ketone bodies as an alternative energy source to glucose. Thus, early initiation of the ketogenic diet (KD) is standard care for Glut1 deficiency syndrome (Glut1DS). Commencement and adherence in older Glut1DS patients is difficult to achieve, leaving few treatment options. Oral D,L-3-hydroxybutyrate (D,L-3-HB) crosses the blood–brain barrier, making it a potential treatment for Glut1DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective case review of patients with Glut1DS under the Adult and Paediatric National Metabolic Service (APNMS) of New Zealand, treated with D,L-3-HB between 2012 and 2023 was performed. Clinical notes, standardised, neuropsychological assessments and subjective data on and off D,L-3-HB were obtained. The best on and off D,L-3-HB measures of working memory (WMI) and processing speed (PSI) were compared to assess the efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>D,L-3-HB was offered to 12 patients with Glut1DS (age 10–52 years). Compliance-dependent improvements in subjective, cognitive and adaptive function were reported by those who were reassessed on-treatment (9/12). Four reported improved PMD. Objective improvements were found in WM (9/9) and PS (6/9). Subjective improvements were reported in patients' health, wellbeing and independence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>KD remains standard of care for Glut1DS, but effective alternatives are lacking for those who do not tolerate this. D,L-3-HB was associated with improved WM, PS and perceived life quality in this small group of patients with Glut1DS, thus providing a potential treatment for this distinct group.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic variability and the gender paradox in the R363C variant of Fabry disease","authors":"Alison C. Leslie,&nbsp;Jeanine Jarnes,&nbsp;Alia Ahmed,&nbsp;Sofia Shrestha,&nbsp;Jeffrey Wang,&nbsp;Chester B. Whitley,&nbsp;Nishitha R. Pillai","doi":"10.1002/jmd2.12466","DOIUrl":"10.1002/jmd2.12466","url":null,"abstract":"<p>Fabry disease is an X-linked lysosomal disease caused by variants in the <i>GLA</i> gene. Although Fabry disease is X-linked, <i>GLA</i> gene variants in females can exhibit a wide range of symptoms, challenging the traditional view of Fabry as an X-linked recessive disease. A family is presented here with a 36-year-old female who is symptomatic with chronic kidney disease and her oligosymptomatic 70-year-old father, both of whom have a heterozygous and hemizygous GLA pathogenic variant, respectively, c.1087C&gt;T (p.R363C). Interestingly, the proband's Lyso-GL-3 levels were lower than her father's despite her more severe clinical presentation. The discordance between clinical severity and Lyso-GL-3 levels, particularly in the context of migalastat therapy, raises questions about the appropriate interpretation and use of this biomarker. The earlier and more severe symptom onset in the female proband suggests the potential role of genetic modifiers or other factors influencing disease expression. This report underscores the complexity of Fabry disease phenotypes and the limitations of current biomarkers in predicting disease severity, particularly in females. The observed paradox between clinical symptoms and biomarker levels suggests the need for a deeper understanding of the underlying mechanisms driving phenotypic variability in Fabry disease.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does p-lactate increase in patients with GSD1 after ingesting a meal with common-size sources of fructose and galactose? Observations from a prospective, non-blinded, crossover pilot study","authors":"Camilla Diana B. Caroee,&nbsp;Allan M. Lund","doi":"10.1002/jmd2.12457","DOIUrl":"10.1002/jmd2.12457","url":null,"abstract":"<p>Ingestion of fructose and galactose may result in elevated lactate concentrations in patients with glycogen storage disease type 1 (GSD1). In this randomized cross-over pilot study, 7 patients with GSD 1a (6) and GSD1b (1) orally consumed a common-size fructose and galactose from either 200 mL of skimmed milk, 200 mL juice or 200 mL water. This was given after a night with their usual dietary treatment using either cornstarch, glycosade or continuous feed. P-lactate and -glucose were measured 2 h before dosing (<i>T</i> = −120 min and −60 min). At baseline (<i>T</i> = 0), p-lactate, p-glucose, p-triglycerides, p-uric acid and p-alanine were measured just before dosing. P-lactate and p-glucose were measured every 30 min for 4 h. Four hours after the consumption (<i>T</i> = 240 min, end-of-test), levels of p-lactate, p-glucose, p-triglycerides, p-uric acid and p-alanine were measured. P-lactate increased in three patients with mean of 0.3 mmol/L (range 0.2–0.6 mmol/L) after consuming milk. The highest level was seen after 60 min. A decrease was seen in three patients. P-lactate increased in four patients with a mean increase at 1.3 mmol/L (range 0.2–2.2 mmol/L) after consuming 200 mL juice. A peak increase was seen after the first 30 min in two patients whereas the peak in the remaining two patients was at 60 min; all values decreased to baseline values after further 60 min. In two patients, p-lactate was unchanged, respectively, decreased after juice ingestion. Calculation of galactose and fructose AUC percentage change after challenge did not reveal consistent increase or decreases.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}