Caregiver Perspective on The Initial Signs and Symptoms of Metachromatic Leukodystrophy

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 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 a caregiver perspective of 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-minute survey and 30-minute semi-structured follow-up telephone interview with 21 MLD caregivers in the United States (n = 10), the United Kingdom (n = 5), and Germany (n = 6). All respondents were primary caregivers of a person with late infantile (n = 13), juvenile (n = 7) or borderline late infantile/juvenile (n = 1) 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, which can be summarized as developmental stagnation, difficulty walking/running, and clonus/tremors, in the absence of notable prior history. Distinctions between late infantile versus juvenile MLD in symptom onset and disease course were also identified. Conclusions This study captures the most frequent caregiver-reported physical, behavioral, and cognitive signs of MLD leading up to diagnosis. The understanding of the caregiver experience at symptom onset sheds light on a critical window of often missed opportunity for earlier diagnosis and therapeutic intervention in MLD.

An international study of caregiver-reported burden and quality of life in metachromatic leukodystrophy

“…As Kehrer, et al, 2011 described, the natural course of MLD typically starts with a period of developmental stagnation, followed by variable periods of plateaus and rapid disease progression, ultimately leading to a point of stabilization at a minimal functional level [22,23]. This path was described by caregivers who participated in this study and is illustrated through the differences in caregiver-reported burden at different points in the individual's disease progression.…”