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The infantile GM2 phenotype is characterized by delays in milestones by 6 months of age, followed by rapid loss of motor, cognitive, and visual function. Advancements in early diagnosis and pharmacotherapies provide promise for improved outcomes. However, the lack of feasible and clinically meaningful clinical outcome assessments for GM2 poses a challenge to characterizing GM2 natural history and selecting clinical trial endpoints. The purpose of this study was to develop a remotely administered infantile GM2 rating scale to measure health-related function in children with infantile GM2. A 2-phase mixed methods design was employed. In phase 1 of the study, 8 families of children with Infantile GM2 completed a natural history survey and a 1:1 semistructured interview to provide caregiver perspectives on the impacts of GM2 on health-related function. In phase 2 of the study, 8 expert clinicians provided feedback via surveys and participated in videoconference-hosted focus groups to refine scale administration and scoring procedures. These methods guided the development of 16 scale items to assess function in 5 health-related function domains: vision, hand and arm use, communication, gross motor, and feeding. This study used caregiver perspectives and expert clinician feedback to develop a remotely administered clinical outcome assessment of clinically meaningful health-related function in children with infantile GM2. Future studies will further evaluate the feasibility, reliability, and validity of the Infantile GM2 Clinical Rating Scale.<\/jats:p>","DOI":"10.1177\/08830738241246703","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T03:40:36Z","timestamp":1714016436000},"page":"161-170","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Development of an Infantile GM2 Clinical Rating Scale: Remote Assessment of Clinically Meaningful Health-Related Function"],"prefix":"10.1177","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0891-2592","authenticated-orcid":false,"given":"Michael","family":"Kiefer","sequence":"first","affiliation":[{"name":"Department of Physical Therapy, College of Health Professions, Virginia Commonwealth University, Richmond, VA, USA"},{"name":"School of Health and Rehabilitation Sciences, MGH Institute of Health Professions, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meg","family":"Simione","sequence":"additional","affiliation":[{"name":"Division of General Academic Pediatrics, Mass General Hospital for Children, Boston, MA, USA"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian S.","family":"Eichler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise L.","family":"Townsend","sequence":"additional","affiliation":[{"name":"School of Health and Rehabilitation Sciences, MGH Institute of Health Professions, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,4,25]]},"reference":[{"key":"bibr1-08830738241246703","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2021.136195"},{"key":"bibr2-08830738241246703","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-0078"},{"key":"bibr3-08830738241246703","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176213"},{"key":"bibr4-08830738241246703","unstructured":"Sehgal DA. Phase 1\/2, open-label clinical study to evaluate the safety and efficacy of intrathecal TSHA-101 gene therapy for treatment of infantile onset GM2 gangliosidosis. clinicaltrials.gov; 2021. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04798235. Accessed November 21, 2021."},{"key":"bibr5-08830738241246703","unstructured":"Sio Gene Therapies. A two-stage, dose-escalation and safety & efficacy study of bilateral intraparenchymal thalamic and intracisternal\/intrathecal administration of AXO-AAV-GM2 in Tay-Sachs or Sandhoff disease. clinicaltrials.gov; 2021. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04669535. Accessed August 18, 2021."},{"key":"bibr6-08830738241246703","doi-asserted-by":"publisher","DOI":"10.3390\/ijns4030024"},{"key":"bibr7-08830738241246703","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2016-0340"},{"key":"bibr8-08830738241246703","unstructured":"World Health Organization. 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