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A cross-sectional study of 21 GA1 patients (15 high excretor, 6 low excretor) compared clinical evaluation, cerebral MRI, neurophysiology, and MR-neurography of the sciatic nerve with magnetization transfer imaging and DTI against 21 age-matched controls, showing frequent neuropathic changes and subtype-dependent 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involvement?",{"text":71,"@type":63},"Clinical evaluation, cerebral MRI, neurophysiology, and MR-neurography of the sciatic nerve were performed, including magnetization transfer imaging and diffusion tensor imaging, with quantitative metrics such as MTR and fractional anisotropy.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},438612,1790716916,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & 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Phenotype in Glutaric Aciduria Type 1  \nFabian Preisner1 | Sven F. Garbade2  | Inga Harting1  | Saskia B. Wortmann3 | Chris Mühlhausen4 | Sabine Heiland1 | Martin Bendszus1 | Stefan Kölker2 | Nikolas Boy2,5  \n1Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany | 2Division of Pediatric Neurology and Metabolic Medicine, Department of Pediatrics I, Heidelberg University Hospital and Heidelberg University, Medical Faculty of Heidelberg, Heidelberg, Germany | 3University Children's Hospital, Paracelsus Medical University, Salzburg, Austria | 4Department of Paediatrics and Adolescent Medicine, University Medical Centre Göttingen, Georg-August University, Göttingen, Germany | 5Clinic for Child Neurology and Social Pediatrics, Children Centre Maulbronn, Maulbronn, Germany  \nCorrespondence: Fabian Preisner (fabian.preisner@med.uni-heidelberg.de)  \nReceived: 13 October 2025 | Revised: 17 December 2025 | Accepted: 23 December 2025  \nAcademic Editor: Johan Van Hove  \nKeywords: biochemical subtype | glutaric acidemia type 1 | glutaric aciduria type 1 | MR neurography | MRI | neurophysiology | polyneuropathy  \nABSTRACT  \nGlutaric aciduria type 1 (GA1) is a neurometabolic disorder characterized by striatal injury in infancy and extrastriatal central nervous system abnormalities, the latter depending on the biochemical subtype. Whether the peripheral nervous system (PNS) is also affected has not been systematically studied. Therefore, we conducted a cross-sectional study of 21 GA1 patients (15 high excretor [HE], 6 low excretor [LE]), identified either by newborn screening (NBS, n = 11) or targeted metabolic diagnostics (TMD, n = 10). All underwent clinical evaluation, cerebral MRI, neurophysiology, and MR-neurography (MRN) of the sciatic nerve with magnetization transfer imaging and diffusion tensor imaging (DTI) . Nerve magnetization transfer ratio (MTR) was analyzed across subgroups and against 21 age-matched controls, while fractional anisotropy (FA) was assessed within the patient cohort. MRN revealed frequent abnormalities in GA1, particularly among HE patients, who showed lower MTR and FA values, indicating neuropathic changes. These alterations correlated with age, extrastriatal MRI abnormalities, and subependymal nodules, but not with striatal lesions or movement disorder. Clinical neuropathic symptoms were rare (4/15 HE patients) yet consistently associated with abnormal MRN. In HE patients exclusively, neurophysiology demonstrated reduced compound motor action potentials, slowed nerve conduction, and prolonged tibial somatosensory evoked potential latencies. Within the HE subgroup, NBS-identified patients showed higher MTR values than those identified by targeted metabolic diagnostics, suggesting less severe nerve involvement. These results expand the GA1 phenotype by demonstrating frequent, predominantly subclinical PNS involvement in HE patients, linked to chronic metabolic toxicity. They underscore the need for further research into long-term complications and therapeutic strategies for HE individuals.  \n\n| Abbreviations: 3-OH-GA, 3-hydroxyglutaric acid; AEC, acute encephalopathic crisis; CMAP, compound muscle action potential; DTI, diffusion tensor imaging; FA, fractional anisotropy; GA, glutaric acid; GA1, glutaric aciduria type 1; GCDH, glutaryl-CoA dehydrogenase; HE, high excretor; LDA, linear discriminant analysis; LE, low excretor; MD, movement disorder; MRI, magnetic resonance imaging; MRN, magnetic resonance neurography; MTI, magnetization transfer imaging; MTR, magnetization transfer ratio; NBS, newborn screening; NCV, nerve conduction velocity; PNS, peripheral nervous system; SEP, somatosensory evoked potential; SNAP, sensory nerve action potential; TMD, targeted metabolic diagnostics.\u003Cbr>Stefan Kölker and Nikolas Boy contributed equally to this work. |\n| --- |\n| This i","cbCaii9krc5l0fGX","https://ap.wps.com/l/cbCaii9krc5l0fGX","pdf",941332,11,"English","# Introduction\n## Peripheral neuropathy in GA1: study rationale\n## Biochemical subtypes and clinical background","[{\"question\":\"What was the main goal of this study in GA1 patients?\",\"answer\":\"To determine whether the peripheral nervous system is also affected in glutaric aciduria type 1 and whether peripheral changes relate to biochemical subtype.\"},{\"question\":\"How were patients and subtypes identified in the study?\",\"answer\":\"Twenty-one GA1 patients were classified as high excretor (HE) or low excretor (LE) based on newborn screening or targeted metabolic diagnostics.\"},{\"question\":\"What imaging and neurophysiology methods were used to assess peripheral involvement?\",\"answer\":\"Clinical evaluation, cerebral MRI, neurophysiology, and MR-neurography of the sciatic nerve were performed, including magnetization transfer imaging and diffusion tensor imaging, with quantitative metrics such as MTR and fractional anisotropy.\"}]","Peripheral Neuropathy Expands the Neurological Phenotype in Glutaric Aciduria Type 1 | PDF",1790685883,28]