{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:55:23Z","timestamp":1785387323292,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Adenylosuccinate synthase 1 (ADSS1)\u2010deficient myopathy is an ultra\u2010rare disease characterized by progressive muscle dysfunction. The objective of this investigation was to employ a noninvasive biomarker approach to phenotype (fine\u2010)motor skills, communication and cognition in adults with ADSS1\u2010deficient myopathy. Five individuals with ADSS1\u2010deficient myopathy and five age\u2010sex\u2010matched healthy controls (HCs) underwent a multimodal evaluation. Assessments included, (i) evaluation of motor performance, (ii) speech and voice production and cognitive test batteries, (iii) patient\u2010reported outcomes, (iv) electrical impedance myography (EIM), (v) musculoskeletal magnetic resonance imaging (MRI), and (vi) plasma proteomics. ADSS1\u2010deficient myopathy participants vs. HCs demonstrated reduced performance on the 9\u2010Hole Peg and grip strength tests as well as lower self\u2010reported mobility. Analysis of speech and voice performance revealed asthenia (vocal weakness) (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02), lower intelligibility (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008), and worse voice quality during the sustained vowel task (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03) in the ADSS1\u2010deficient myopathy cohort. Cognitive functioning remained unaffected in patients with ADSS1\u2010deficient myopathy. On EIM, ADSS1\u2010deficient myopathy participants vs. HCs, demonstrated a pattern of higher resistance and lower reactance and phase across upper\u2010 and lower\u2010extremity measurements, indicative of poorer muscle health, with large effect sizes (Cliff's\n                    <jats:italic>\u03b4<\/jats:italic>\n                    \u2009=\u20090.5\u20130.9). MRI revealed intramuscular fat infiltration, particularly in posterior compartments of the upper leg (e.g., biceps femoris). Proteomics indicated reduced (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04) Neurotrophin\u20103 (NTF3; implicated in neuronal development, survival, and differentiation) levels in the ADSS1\u2010deficient myopathy cohort relative to HCs. Lower NTF3 levels associated with poorer performance on hand\u2010motor tasks as well as higher resistance and lower reactance and phase on EIM. This study highlighted the value of multimodal phenotyping for quantifying disease expression and advancing monitoring strategies in ADSS1\u2010deficient myopathy. This multimodal investigation demonstrates that integrating electrical impedance myography with quantitative motor, speech, musculoskeletal imaging, and proteomic assessments provides a sensitive and noninvasive research framework for capturing neuromuscular dysfunction and functional disease burden in patients with ADSS1\u2010deficient myopathy, thereby supporting the current biomarker strategy for refined phenotyping and longitudinal disease monitoring in this ultra\u2010rare condition.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70193","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T12:57:37Z","timestamp":1776949057000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multimodal Noninvasive Biomarker Characterization of Structural and Functional Alterations in\n                    <scp>ADSS1<\/scp>\n                    \u2010Deficient Myopathy"],"prefix":"10.1002","volume":"49","author":[{"given":"Merve Ko\u00e7","family":"Yeked\u00fcz","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Pediatric Metabolism Ankara University, Faculty of Medicine  Ankara T\u00fcrkiye"},{"name":"Rare Diseases Application and Research Center Ankara University  Ankara T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"van Gool","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Neurology Mental Health and Neuroscience Research Institute, Maastricht University  Maastricht Limburg the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2636-221X","authenticated-orcid":false,"given":"Hanne","family":"van der Heijden","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buket Sonbas","family":"Cobb","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Electrical and Electronic Engineering Harran University  Sanliurfa T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nehal","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Radiology, Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0583-8945","authenticated-orcid":false,"given":"Georgina","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Audiology and Speech Pathology The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara A.","family":"Timpani","sequence":"additional","affiliation":[{"name":"Inherited and Acquired Myopathies Program Australian Institute for Musculoskeletal Science  St Albans Victoria Australia"},{"name":"Department of Medicine\u2010Western Health Melbourne Medical School, the University of Melbourne  St Albans Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5530-9692","authenticated-orcid":false,"given":"Julie","family":"Shulman","sequence":"additional","affiliation":[{"name":"Department of Physical and Occupational Therapy Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Rameh","sequence":"additional","affiliation":[{"name":"Department of Radiology, Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan E.","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Immunology, Boston Children's Hospital Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"LeSon","sequence":"additional","affiliation":[{"name":"Division of Immunology, Boston Children's Hospital Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pui Y.","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Immunology, Boston Children's Hospital Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam P.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Audiology and Speech Pathology The University of Melbourne  Parkville Victoria Australia"},{"name":"Redenlab Ltd  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8967-8640","authenticated-orcid":false,"given":"Walla","family":"Al\u2010Hertani","sequence":"additional","affiliation":[{"name":"Division of Metabolic Disorders Children's Hospital of Orange County (CHOC) Rady Children's Health  Orange California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4165-8901","authenticated-orcid":false,"given":"Hyung Jun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yonsei University College of Medicine Gangnam Severance Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Rybalka","sequence":"additional","affiliation":[{"name":"Inherited and Acquired Myopathies Program Australian Institute for Musculoskeletal Science  St Albans Victoria Australia"},{"name":"Department of Medicine\u2010Western Health Melbourne Medical School, the University of Melbourne  St Albans Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6375-3312","authenticated-orcid":false,"given":"Seward B.","family":"Rutkove","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaymin","family":"Upadhyay","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School  Boston 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