{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:18:43Z","timestamp":1788445123016,"version":"build-2803163510"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>\n                    Parkinson's disease (PD) is a common neurodegenerative disorder, and pathogenic variants in\n                    <jats:italic>GBA1<\/jats:italic>\n                    are among its most frequent genetic risk factors. Biallelic pathogenic\n                    <jats:italic>GBA1<\/jats:italic>\n                    variants cause Gaucher Disease (GD). In patients with parkinsonism and two detected\n                    <jats:italic>GBA1<\/jats:italic>\n                    variants, the absence of biochemical confirmation and allele phasing may make it difficult to determine whether the neurological presentation occurs in the context of GD or represents\n                    <jats:italic>GBA1<\/jats:italic>\n                    -associated PD. We report a 35-year-old man with a 7-months history of progressive, asymmetric parkinsonism. Dopamine transporter PET\/CT showed reduced bilateral striatal uptake, more pronounced on the right. Abdominal CT showed asplenia, and laboratory eveluation revealed mild thrombocytopenia, marked hyperferritinemia, polyclonal hypergammaglobulinemia, proteinuria, and microscopic hematuria. Whole-exome sequencing followed by Sanger validation identified two heterozygous\n                    <jats:italic>GBA1<\/jats:italic>\n                    variants classified as pathogenic: c.1448T&amp;gt;C (p.Leu483Pro; legacy name L444P) and c.1342G&amp;gt;C (p.Asp448His; legacy name D409H). Family testing supported the familial occurrence of both variants but did not establish their allelic phase. Because glucocerebrosidase activity and GD biomarkers were not measured, type 1 Gaucher disease (GD1) remained suspected rather than confirmed. During hospitalization, dopaminergic therapy was associated with clinical improvement, with the OFF-state UPDRS-III score decreasing from 21 at admission to 10 at discharge. The clinical value of this case lies in the convergence of early-onset parkinsonism, remote visceral and hematologic findings, the co-occurrence of p.Leu483Pro and p.Asp448His with unresolved allelic phase, and the familial occurrence of both variants. It underscores the need for biochemical confirmation,\n                    <jats:italic>GBA1<\/jats:italic>\n                    -specific phase-resolved testing, and longitudinal multisystem assessment before the diagnosis of GD1 and the associated familial risks can be reliably defined.\n                  <\/jats:p>","DOI":"10.3389\/fnins.2026.1920271","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:58:51Z","timestamp":1788443931000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Early-onset parkinsonism as a presenting feature of suspected type 1 Gaucher disease with two pathogenic GBA1 variants: a case report"],"prefix":"10.3389","volume":"20","author":[{"given":"Yuqin","family":"Sun","sequence":"first","affiliation":[{"name":"The Affiliated Hospital of Guizhou Medical University, Guiyang","place":["Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihan","family":"Ni","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Guizhou Medical University, Guiyang","place":["Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunli","family":"Yu","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Guizhou Medical University, Guiyang","place":["Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","article-title":"Parkinson's disease","volume":"397","author":"Bloem","year":"2021","journal-title":"Lancet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.3390\/genes16121496","article-title":"Underlying mechanisms of GBA1 in parkinson's disease and dementia with lewy bodies: narrative review","volume":"16","author":"Bougea","year":"2025","journal-title":"Genes"},{"key":"B3","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s10545-010-9055-0","article-title":"The risk of parkinson's disease in type 1 Gaucher disease","volume":"33","author":"Bultron","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"973","DOI":"10.3760\/cma.j.cn113694-20200331-00233","volume":"53","year":"2020"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1007\/s00415-018-8908-6","article-title":"The motor and cognitive features of parkinson's disease in patients with concurrent Gaucher disease over 2 years: a case series","volume":"265","author":"Collins","year":"2018","journal-title":"J. Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"S12","DOI":"10.1002\/ajh.24063","article-title":"Gaucher disease types 1 and 3: Phenotypic characterization of large populations from the ICGG Gaucher registry","volume":"90","author":"Grabowski","year":"2015","journal-title":"Am. J. Hematol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1002\/humu.20676","article-title":"LaMarca ME, Scott CR, Sidransky E. Gaucher disease: mutation and polymorphism spectrum in the Glucocerebrosidase Gene (GBA)","volume":"29","author":"Hruska","year":"2008","journal-title":"Hum. Mutat."},{"key":"B8","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1136\/jnnp.2007.131045","article-title":"Parkinson's disease: clinical features and diagnosis","volume":"79","author":"Jankovic","year":"2008","journal-title":"J Neurol. Neurosurg. Psychiatry"},{"key":"B9","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/s41531-025-01060-6","article-title":"Classification of GBA1 variants and their impact on parkinson's disease: an in silico score analysis","volume":"11","author":"Lanore","year":"2025","journal-title":"NPJ Parkinsons Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e0188","DOI":"10.1097\/MD.0000000000010188","article-title":"Type I Gaucher disease with bullous pemphigoid and Parkinson disease: a case report","volume":"97","author":"Le Peillet","year":"2018","journal-title":"Medicine"},{"key":"B11","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1016\/j.kint.10","article-title":"Executive summary of the KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease: known knowns and known unknowns","volume":"105","author":"Levin","year":"2023","journal-title":"Kidney Int."},{"key":"B12","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1007\/s10571-015-0176-8","article-title":"Gaucher-associated parkinsonism","volume":"35","author":"Li","year":"2015","journal-title":"Cell Mol. Neurobiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1186\/s12882-023-03163-9","article-title":"Gaucher disease in a patient with membranoproliferative glomerulonephritis: case report","volume":"24","author":"Liang","year":"2023","journal-title":"BMC Nephrol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/8904_2011_48","article-title":"A 12-year follow-up study on a case of early-onset parkinsonism preceding clinical manifestation of Gaucher disease","volume":"3","author":"Machaczka","year":"2012","journal-title":"JIMD Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1038\/s41531-022-00397-6","article-title":"Lysosomal lipid alterations caused by glucocerebrosidase deficiency promote lysosomal dysfunction, chaperone-mediated-autophagy deficiency, and alpha-synuclein pathology","volume":"8","author":"Navarro-Romero","year":"2022","journal-title":"NPJ Parkinsons Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1203\/01.PDR.0000049515.79882.94","article-title":"LaMarca ME, Stubblefield BK, et al. Myoclonic epilepsy in Gaucher disease: genotype-phenotype insights from a rare patient subgroup","volume":"53","author":"Park","year":"2003","journal-title":"Pediatr. Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1006\/bmme.1996.0077","article-title":"The glucocerebrosidase D409H mutation in Gaucher disease","volume":"59","author":"Pasmanik-Chor","year":"1996","journal-title":"Biochem. Mol. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.3760\/cma.j.cn112137-20200222-00405","article-title":"Expert consensus on diagnosis and treatment of adult Gaucher disease in China","volume":"100","year":"2020","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"B19","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.jbspin.12","article-title":"Prevalence of autoantibodies in the course of Gaucher disease type 1: a multicenter study comparing Gaucher disease patients to healthy subjects","volume":"85","author":"Serratrice","year":"2016","journal-title":"Joint Bone Spine"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e70087","DOI":"10.1111\/jcmm.70087","article-title":"Old disease-New reflections: Gaucher, immunity, and inflammation","volume":"28","author":"Soroglu","year":"2024","journal-title":"J. Cell Mol. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"441","DOI":"10.3390\/ijms18020441","article-title":"A review of Gaucher disease pathophysiology, clinical presentation and treatments","volume":"18","author":"Stirnemann","year":"2017","journal-title":"Int J Mol Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1006\/mgme.2001.3201","article-title":"Gaucher disease and parkinsonism: a phenotypic and genotypic characterization","volume":"73","author":"Tayebi","year":"2001","journal-title":"Mol. Genet. Metab."},{"key":"B23","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/S1096-7192(03)00071-4","article-title":"Gaucher disease with parkinsonian manifestations: does glucocerebrosidase deficiency contribute to a vulnerability to parkinsonism?","volume":"79","author":"Tayebi","year":"2003","journal-title":"Mol Genet Metab."},{"key":"B24","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1038\/s42003-022-03610-7","article-title":"Comprehensive short and long read sequencing analysis for the Gaucher and parkinson's disease-associated GBA gene","volume":"5","author":"Toffoli","year":"2022","journal-title":"Commun. Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/S1474-4422(21)00030-2","article-title":"Challenges in the diagnosis of parkinson's disease","volume":"20","author":"Tolosa","year":"2021","journal-title":"Lancet Neurol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1007\/s00702-022-02531-3","article-title":"Glucocerebrosidase mutations and parkinson disease","volume":"129","author":"Vieira","year":"2022","journal-title":"J. Neural. Transm."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2144","DOI":"10.1002\/mds.30006","article-title":"Consensus guidance for genetic counseling in GBA1 variants: a focus on parkinson's disease","volume":"39","author":"Vieira","year":"2024","journal-title":"Move Dis."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1920271\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:58:54Z","timestamp":1788443934000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1920271\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":27,"alternative-id":["10.3389\/fnins.2026.1920271"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2026.1920271","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"article-number":"1920271"}}