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. 2022 Oct 4;17(1):370.
doi: 10.1186/s13023-022-02518-z.

Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy

F Eichler  1   2 , Caroline Sevin  3 , M Barth  4 , F Pang  5 , K Howie  6 , M Walz  6 , A Wilds  6 , C Calcagni  6 , C Chanson  7 , L Campbell  7
Affiliations

Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy

F Eichler et al. Orphanet J Rare Dis. .

Abstract

Background: Metachromatic leukodystrophy (MLD), a relentlessly progressive and ultimately fatal condition, is a rare autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme arylsulfatase A (ARSA). Historically management has been palliative or supportive care. Hematopoietic stem cell transplantation is poorly effective in early-onset MLD and benefit in late-onset MLD remains controversial. Hematopoietic stem cell gene therapy, Libmeldy (atidarsagene autotemcel), was recently approved by the European Medicines Agency for early-onset MLD. Treatment benefit is mainly observed at an early disease stage, indicating the need for early diagnosis and intervention. This study contributes insights into the caregiver language used to describe initial MLD symptomatology, and thereby aims to improve communication between clinicians and families impacted by this condition and promote a faster path to diagnosis.

Results: Data was collected through a moderator-assisted online 60-min survey and 30-min semi-structured follow-up telephone interview with 31 MLD caregivers in the United States (n = 10), France (n = 10), the United Kingdom (n = 5), and Germany (n = 6). All respondents were primary caregivers of a person with late infantile (n = 20), juvenile (n = 11) or borderline late infantile/juvenile (n = 1) MLD (one caregiver reported for 2 children leading to a sample of 32 individuals with MLD). Caregivers were asked questions related to their child's initial signs and symptoms, time to diagnosis and interactions with healthcare providers. These results highlight the caregiver language used to describe the most common initial symptoms of MLD and provide added context to help elevate the index of suspicion of disease. Distinctions between caregiver descriptions of late infantile and juvenile MLD in symptom onset and disease course were also identified.

Conclusions: This study captures the caregiver description of the physical, behavioral, and cognitive signs of MLD prior to diagnosis. The understanding of the caregiver language at symptom onset sheds light on a critical window of often missed opportunity for earlier diagnosis and therapeutic intervention in MLD.

Keywords: Caregiver experience; Caregiver language; Diagnostic delay; Disease onset; Early-onset; Initial symptoms; Juvenile; Late infantile; MLD; Metachromatic leukodystrophy.

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Conflict of interest statement

Data presented in this paper was collected as part of a study sponsored and funded by Orchard Therapeutics, Ltd., London, UK and was designed through a collaboration among the sponsor and Magnolia Innovation, LLC, Hoboken, NJ. Data was collected by Magnolia Innovation. Dr. Eichler has previously served on an advisory board for Orchard Therapeutics but has no current conflicts of interest with Orchard nor Magnolia Innovation. Dr. Sevin and Dr. Barth have no current conflicts of interest with Orchard nor Magnolia Innovation. Mr. Pang, Ms. Chanson, and Dr. Campbell are previous or current employees of sponsor, Orchard Therapeutics, Ltd. Mr. Calcagni, Mr. Howie, Mr. Walz, and Ms. Wilds are previous or current employees of Magnolia Innovation, LLC.

Figures

Fig. 1
Fig. 1
Constellations of caregiver-reported initial symptoms by onset type
Fig. 2
Fig. 2
Time from symptom onset to first medical consult
See this image and copyright information in PMC

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