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. 2025 Aug 4;20(1):399.
doi: 10.1186/s13023-025-03632-4.

Single large-scale mitochondrial DNA deletion syndromes: scientific and family conference optimizes the collection of rare disease research outcomes

Laura E MacMullen #  1 , Elizabeth Reynolds #  2 , Marissa Weis  1 , Ibrahim George-Sankoh  1 , Sara Nguyen  1 , Katelynn D Stanley  1 , Mariya Redko  1 , Maria Poblete  1 , Amy C Goldstein  1   3 , Rebecca D Ganetzky  4   5   6
Affiliations

Single large-scale mitochondrial DNA deletion syndromes: scientific and family conference optimizes the collection of rare disease research outcomes

Laura E MacMullen et al. Orphanet J Rare Dis. .

Abstract

Background: The SLSMDS Research Network is a collaborative network comprising patient advocates, researchers, clinicians, and affected families seeking to improve outcomes for individuals with single large-scale mitochondrial DNA deletion syndromes (SLSMDS). Building off of jointly developed research infrastructures, including a patient registry and natural history study, advocates and clinicians cohosted the SLSMDS Family and Scientific Conference, enabling the collection of patient data from an ultra-rare and geographically dispersed patient population. Here we describe the data collection procedures for single-time point laboratory assessments and patient reported outcomes for a subset of individuals with SLSMDS.

Results: Utilizing a reproducible model of rare disease data collection, we expand our understanding of the common psychiatric manifestations, describe variability in terms of self-care and quality of life, and emphasize potential biomarkers for individuals with SLSMDS.

Conclusion: Our study describes how efficient patient-researcher partnerships can develop and sustain novel mechanisms to collect rare disease data, improve our understanding of the natural history of these disorders, and support development of future treatments.

Keywords: Chronic progressive external ophthalmoplegia; Conference; Kearns Sayre syndrome; Patient-reported outcomes; Pearson syndrome; Rare disease; Single large‐scale mitochondrial deletion syndromes; mtDNA.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The research study was reviewed and approved by Castle Institutional Review Board (IRB) and accepted via Cooperative IRB Review by the Institutional Review Board at the Children’s Hospital of Philadelphia. Research was conducted in conformance with 45 CFR 46 standards for the protection of human participants. Consent for publication: Not applicable. Competing interests: ER declares she is the founder of The Champ Foundation and a parent of a child with Pearson syndrome. RDG declares that she receives consulting funds from Minovia Therapeutics and Nurture Genomics. LEM, MW, IGS, SN, KDS, MR, MP, and ACG have no competing interests to disclose.

Figures

Fig. 1
Fig. 1
Participant inclusion and completed assessments. Schematic outlining the process of conference registration and research consent. The number of participants involved at each stage is indicated to the left of the description
Fig. 2
Fig. 2
Z-scores for height. Z-scores were calculated using sex, age, height, and population averages from the U.S. Department of Health and Human Services Centers for Disease Control and Prevention. A Z-Score of zero represents the population mean and the shaded region indicates values that fall within 2 standard deviations above or below the population mean
Fig. 3
Fig. 3
EQ-5D-Y visual analog scale (EQ VAS) rating and neuro-QOL anxiety T-score. a EQ-5D-Y VAS Rating ranges from 0 (“worst health you can imagine) to 100 (“best health you can imagine”); b Neuro-QOL Anxiety scale T-Score with a normative mean of 50 and standard deviation of 10
Fig. 4
Fig. 4
MASC-2 total and sub-scale T-scores. Scores are normed on a T-Scale with a mean of 50 and standard deviation of 10. Scores are colored by T-Score severity classification
See this image and copyright information in PMC

References

    1. Goldstein A, Falk MJ. Mitochondrial DNA deletion syndromes. In: Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, editors. Adam MP. Seattle (WA): GeneReviews; 1993. - PubMed
    1. Broomfield A, Sweeney MG, Woodward CE, et al. Paediatric single mitochondrial DNA deletion disorders: an overlapping spectrum of disease. J Inherit Metab Dis. 2015;38(3):445–57. 10.1007/s10545-014-9778-4. - PMC - PubMed
    1. Roennow A, Sauve M, Welling J, et al. Collaboration between patient organisations and a clinical research sponsor in a rare disease condition: learnings from a community advisory board and best practice for future collaborations. BMJ Open. 2020;10(12):e039473. 10.1136/bmjopen-2020-039473. - PMC - PubMed
    1. Velvin G, Hartman T, Bathen T. Patient involvement in rare diseases research: a scoping review of the literature and mixed method evaluation of Norwegian researchers’ experiences and perceptions. Orphanet J Rare Dis. 2022;17(1):212. 10.1186/s13023-022-02357-y. - PMC - PubMed
    1. Reynolds E, Byrne M, Ganetzky R, et al. Pediatric single large-scale mtDNA deletion syndromes: the power of patient reported outcomes. Mol Genet Metab. 2021;134(4):301–8. 10.1016/j.ymgme.2021.11.004. - PubMed

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