Practical Approaches and Knowledge Gaps in the Care for Children With Leukodystrophies

Keller, Stephanie; Mallack, Eric J.; Rubin, Jennifer; Accardo, Jennifer; Brault, Jennifer; Corre, Camille; Elizondo, Camila; Garafola, Jennifer; Jackson-Garcia, April C.; Rhee, Jullie; Seeger, Elisa; Shullanberger, Kaprice C.; Tourjee, Amanda; Trovato, Melissa; Waldman, Amy; Wallace, Jenna L.; Wallace, Michael R.; Werner, Klaus; White, Angela; Ess, Kevin C.; Becker, Catherine; Eichler, Florian

doi:10.1177/0883073820946154

Cited by 12 publications

(5 citation statements)

References 83 publications

(174 reference statements)

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“…The mainstay of management is early neurorehabilitative therapy and symptomatic management, including seizure control (Keller et al ., 2021; Shukla et al ., 2021). Fingolimod (FTY720) was explored as a possible treatment for DEGS1 -related HLD (Pant et al ., 2019).…”

Section: Discussionmentioning

confidence: 99%

DEGS1-related leukodystrophy: a clinical report and review of literature

Wong

Thomas

Lim

et al. 2023

Clinical Dysmorphology

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Background: Leukodystrophies are a heterogeneous group of disorders affecting the white matter of the central nervous system, with or without affecting the peripheral nervous system. Biallelic variants in DEGS1, coding for desaturase 1 (Des1) protein, were recently reported to be associated with hypomyelinating leukodystrophy (HLD), a subclass of leukodystrophies where the formation of the myelin sheath is affected.Methods Genomic sequencing was performed on our index patient with severe developmental delay, severe failure to thrive, dystonia, seizures, and hypomyelination on brain imaging. Sphingolipid analysis was performed and dihydroceramide/ceramide (dhCer/Cer) ratios were obtained by the measurement of ceramide and dihydroceramide species.Results A homozygous missense variant was identified in DEGS1 (c.565A > G:p Asn189Asp). The identified DEGS1 variant has been annotated as "conflicting reports of pathogenicity" on ClinVar. Follow-up sphingolipid analysis on our patient showed significantly raised dhCer/ Cer and this was consistent with dysfunction of the Des1 protein, providing additional evidence to support the pathogenicity of this variant. ConclusionWhile rare, pathogenic variants in DEGS1 should be considered in patients with HLD phenotype. To date, 25 patients have been reported across four studies on DEGS1-related HLD, and, in this report, we summarize the literature. More such reports will enable deeper phenotypic characterization of this disorder.

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Section: Discussionmentioning

confidence: 99%

DEGS1-related leukodystrophy: a clinical report and review of literature

Wong

Thomas

Lim

et al. 2023

Clinical Dysmorphology

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“…Respondents dedicate the vast majority of their time caring for their child with MLD. In addition to the time spent on outpatient and hospital visits, caregiving may also involve addressing activities of daily living such as bathing, dressing, or feeding the child with MLD [19], and tending to the medical needs of their child, which could include administering medications and frequently repositioning of a bed-ridden child [20]. These activities together can consume nearly two-thirds or more of a caregiver's day, or six additional hours of care outside of the normal responsibilities of caring for a child.…”

Section: Time Investmentmentioning

confidence: 99%

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

Sevin¹,

Barth

Wilds

et al. 2022

Orphanet J Rare Dis

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Background Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder caused by mutations in the arylsulfatase A gene. Until now, there has been little information on the burden of MLD on patients and their caregivers. This multinational study aims to quantify caregiver-related impacts of MLD across several key domains including symptoms, treatment burden, time investment, social and emotional well-being, and professional and financial impact. Results Data were collected through moderator-assisted web survey and telephone interviews. The survey was developed with extensive input from clinical experts and MLD patient advocacy groups. The EQ-5D-5L questionnaire was administered during follow-up interviews. The total sample consisted of parents of MLD patients in the US (n = 10), France (n = 10), Germany (n = 6), UK (n = 5), Belgium (n = 1), and Norway (n = 2). The impact of MLD is evident from the EQ-5D-5L scores, which indicate utility values for caregivers below respective national population norms and a higher proportion of caregivers reporting problems with anxiety/depression. Time involved for care was demonstrated by a mean of 4.1 inpatient and 29.6 outpatient hospital visits in the previous 12-month period. These commitments place stress on familial relationships with 50% of caregivers reporting their child’s MLD diagnosis had negatively impacted their relationship with their spouse/partner. Professionally, 76.5% of caregivers stopped working or switched to part-time employment following their child’s MLD diagnosis, and most acknowledged caring for their child had affected their potential for career progression or promotion. Differences are also observed based on late infantile versus juvenile onset MLD, time since diagnosis, and for transplanted patients versus those who received palliative care only. Conclusions This multinational study demonstrates that MLD consistently negatively affects many aspects of caregivers’ lives including health, relationships, and professional status, irrespective of location. We expect that the results of this study are generalizable to other countries. This study enhances our understanding of MLD caregiver impacts, which could improve patient care and assist in identifying support for individuals with MLD and their families.

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“…Leukodystrophies (LDs) are a heterogeneous group of disorders with widely varying clinical manifestations and pathological mechanisms, afflicting the brain's white matter, with or without peripheral nervous system involvement [1]. These are rare diseases, affecting approximately [1] in 7500 individuals [2].…”

Section: Introductionmentioning

confidence: 99%

Occupational Therapy Intervention in the Child with Leukodystrophy: Case Report

Simeon,

Berardi,

Valente

et al. 2023

Children

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Background: There are many different types of Leukodystrophies. Specifically, children with hypomyelination and congenital cataract syndrome (HCC) in addition to motor retardation development, hypotonia and progressive spastic paraplegia, associated with cerebellar ataxia and peripheral neuropathy, have early bilateral cataracts and intellectual disability as pathognomonic symptoms. HCC rehabilitation treatment is not well defined, but a significant amount of evidence in the literature has demonstrated the effectiveness of occupational therapy (OT) treatment in children with similar symptomatology. For this reason, the aim of this study was to describe the improvement in the autonomies and social participation of a child with HCC following OT treatment. Methods: A.E. was a 9-year-old child with HCC with severe intellectual disability. OT intervention lasted 3 months biweekly and each session lasted 45 min. Each session was divided into two parts: The first part aimed to increase the child’s active involvement through activities; the second part involved training in Activities of Daily living (ADL). The outcome measures were: ABILHAND-Kids; Pediatric Evaluation of Disability Inventory; Comprehensive OT Evaluation Scale; ADL and Instrumental Activities of Daily Living. Results: A.E.’s outcome measure reported an improvement from an autonomy standpoint and in the child’s general activity participation; there was also an increase in A.E.’s interpersonal skills. Conclusion: OT treatment improved A.E.’s autonomy.

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Practical Approaches and Knowledge Gaps in the Care for Children With Leukodystrophies

Cited by 12 publications

References 83 publications

DEGS1-related leukodystrophy: a clinical report and review of literature

DEGS1-related leukodystrophy: a clinical report and review of literature

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

Occupational Therapy Intervention in the Child with Leukodystrophy: Case Report

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