Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May:166:81-87.
doi: 10.1016/j.pediatrneurol.2025.02.011. Epub 2025 Feb 27.

POLR3-Related Leukodystrophy: A Qualitative Study on Parents' Experiences With the Health Care System

Adam Le  1 , Kelly-Ann Thibault  2 , Pouneh Amir Yazdani  2 , Enrico Bertini  3 , Francesco Nicita  3 , Daniela Pohl  4 , Sunita Venkateswaran  5 , Stephanie Keller  6 , Deborah Renaud  7 , Dolores Gonzales Moron  8 , Marcelo Kauffman  8 , Danilo De Assis Pereira  9 , Adeline Vanderver  10 , Maxime Morsa  11 , Geneviève Bernard  12
Affiliations

POLR3-Related Leukodystrophy: A Qualitative Study on Parents' Experiences With the Health Care System

Adam Le et al. Pediatr Neurol. 2025 May.

Abstract

Background: POLR3-related hypomyelinating leukodystrophy (POLR3-HLD) is a rare, inherited neurodegenerative disorder affecting white matter development of the central nervous system. This disorder is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism (4H leukodystrophy). Patients with POLR3-HLD require complex and specialized care; however, due to its rarity and limited awareness, parents often assume additional roles as experts and advocates for their child(ren). We aimed to understand parents' experiences navigating the health care landscape and to identify potential targets for improvement.

Methods: Research team members conducted semi-structured interviews with parents of patients with POLR3-HLD. Interview questions focused on the diagnostic odyssey, availability and access to care, and the perceived quality of care. Interviews were recorded, transcribed, coded, and analyzed using reflexive thematic analysis, and themes surrounding parents' health care experiences were developed.

Results: Nineteen semi-structured interviews were conducted with an international cohort of 24 parents between March and October 2023. Four themes were developed: existing barriers in accessing care, limited knowledge in diagnosis and care, parents as experts and advocates of their child(ren)'s care, and perceived superior care by leukodystrophy specialists. Many parents expressed feeling alone and uncertain, with little guidance provided to them. They also identified perceived gaps in care and challenges faced but found comfort when treated by leukodystrophy experts in specialty clinics.

Conclusions: This study will help better inform health care providers, administrators, and policymakers to expand and improve access to quality care for patients with POLR3-HLD and their families. These conclusions may also be generalizable to other rare diseases.

Keywords: Access to care; Health care experiences; POLR3-related leukodystrophy; Parents/caregivers; Quality of care; Rare disease; Thematic analysis.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest Dr. Bertini serves on the Medical and Scientific Advisory Board of the United Leukodystrophy Foundation and the European Leukodystrophy Association and is a member of the Vanishing White Matter Consortium. He is on the editorial board of Neuromuscular Disorders and is a site investigator for the Alexander disease trial of Ionis (2021 to present). He is a consultant for Roche, Orchard Therapeutics, Biogen, PTC, and Pfizer. Dr. Keller is/was a consultant for Veristat, LLC (2021); Orchard Therapeutics (2023); and the Applied Therapeutics (2024). She is/was a site investigator for the Alexander disease trial of Ionis (2021 to present) and the Pelizaeus-Merzbacher disease trial of Ionis (2024 to present). She serves on the Board of Directors for the United Leukodystrophy Foundation. She is the site PI for the NIH-funded GLIA-CTN (2019 to present) and the Aicardi-Goutières syndrome outcomes study. She was also an ad hoc consultant for the FDA Cellular, Tissue and Gene Therapeutics Committee. Dr. Vanderver receives grant and in-kind support for translational research without personal compensation from Affinia, Biogen, Boehringer Ingelheim, Eli Lilly, Illumina, Ionis, Homology, Myrtelle, Orchard Therapeutics, Passage Bio, Sana, Sanofi, Synaptixbio, and Takeda. Dr. Bernard is/was a consultant for Calico (2023-present), Orchard Therapeutics (2023), Passage Bio Inc (2020-2022), and Ionis (2019). She is/was a site investigator for the Alexander disease trial of Ionis (2021 to present), Metachromatic leukodystrophy of Shire/Takeda (2020 to 2021), Krabbe (2021 to 2023) and GM1 gene therapy trials of Passage Bio (2021 to 2024), GM1 natural history study from the University of Pennsylvania sponsored by Passage Bio (2021 to present), and Adrenoleukodystrophy/hematopoietic stem cell transplantation natural history study of Bluebird Bio (2019) and a site subinvestigator for the MPS II gene therapy trial of Regenxbio (2021 to present) and the MPS II clinical trial of Denali (2022 to present). She has received unrestricted educational grants from Takeda (2021 to 2022). She serves on the Scientific Advisory Board of the Pelizaeus-Merzbacher Foundation, the Yaya Foundation Scientific and Clinical Advisory Council, and is the Chair of the Medical and Scientific Advisory Board of the United Leukodystrophy Foundation. She is a member of the Vanishing White Matter Consortium, the H-ABC Clinical Advisory Board, and MLC Clinical Expert Consortium, and the Chair of the POLR3-related (4H) Leukodystrophy Consortium. She is on the editorial boards of Neurology Genetics, Frontiers in Neurology – Neurogenetics, and Journal of Medical Genetics. All other authors have no conflicts of interest relevant to this article to disclose.

Similar articles

See all similar articles

References

    1. Vanderver A, Prust M, Tonduti D, et al. Case definition and classification of leukodystrophies and leukoencephalopathies. Mol Genet Metab. 2015;114:494–500. - PMC - PubMed
    1. van der Knaap MS, Bugiani M. Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms. Acta Neuropathol. 2017;134:351–382. - PMC - PubMed
    1. Vrij-van den Bos S, Hol JA, La Piana R, et al. 4H leukodystrophy: a brain magnetic resonance imaging scoring system. Neuropediatrics. 2017;48:152–160. - PubMed
    1. Bernard G, Chouery E, Putorti ML, et al. Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy. Am J Hum Genet. 2011;89:415–423. - PMC - PubMed
    1. Tetreault M, Choquet K, Orcesi S, et al. Recessive mutations in POLR3B, encoding the second largest subunit of Pol III, cause a rare hypomyelinating leukodystrophy. Am J Hum Genet. 2011;89:652–655. - PMC - PubMed

Substances

LinkOut - more resources