Leukodystrophies and Lysosomal Storage Disorders

Escolar, Maria L.; Aldenhoven, Mieke

doi:10.1007/978-1-4614-8357-1_4

Cited by 3 publications

(3 citation statements)

References 408 publications

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“…While ERT has been found to result in reductions in hepatosplenomegaly, urinary GAG excretion and sleep apnea, as well as improvements in growth, physical endurance, and joint range of motion 7 , HCT has resulted in better GAG clearance and metabolic correction than with ERT 11 . Outcome of successful HCT includes improved multi-system functioning 3 , 9 , 10 , 24 , 28 , such that GAG are reduced in soft tissue such as the liver, spleen, lungs, airway, marrow, facies, and the vascular system. Although guidelines recommend HCT for MPS IH, often ERT is used as an adjunctive therapy to improve the health status of patients prior to HCT, and ERT in the peri-transplant period has been used with the intent of decreasing morbidity and mortality associated with HCT 18 , 29 , 30 .…”

Section: Discussionmentioning

confidence: 99%

“…With more favorable HCT outcomes being made possible by newborn screening, there are still challenges associated with transplant. First, it is recognized that metabolic correction is not uniformly distributed among organ systems, as differential delivery of enzyme to the target organs is difficult to measure, and problems remain, particularly in the skeletal, nervous, and cardiac systems, despite full engraftment of enzyme competent donor hematopoietic cells following transplantation 3 , 10 , 24 , 35 , 36 . Thus many transplanted children show continued cognitive and physical impairments, with severity related to age at HCT 3 , 9 , 24 , 34 .…”

Section: Discussionmentioning

confidence: 99%

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Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison

Eisengart

Rudser

Xue

et al. 2018

Genetics in Medicine

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Purpose Early treatment is critical for mucopolysaccharidosis type I (MPS I), justifying its incorporation into newborn screening. Enzyme replacement therapy (ERT) treats MPS I, yet presumptions that ERT cannot penetrate the blood-brain barrier (BBB) support recommendations that hematopoietic cell transplantation (HCT) treat the severe, neurodegenerative form (Hurler syndrome). Ethics preclude randomized comparison of ERT to HCT, but insight into this comparison is presented with an international cohort of patients with Hurler syndrome who received long-term ERT from a young age. Methods Long-term survival and neurologic outcomes were compared among three groups of patients with Hurler syndrome: 18 treated with ERT monotherapy (ERT group), 54 who underwent HCT (HCT group), and 23 who received no therapy (Untreated). All were followed starting before age 5 years. A sensitivity analysis restricted age below 3 years. Results Survival was worse when comparing ERT versus HCT, and Untreated versus ERT. The cumulative incidences of hydrocephalus and cervical spinal cord compression were greater in ERT versus HCT. Findings persisted in the sensitivity analysis. Conclusion As newborn screening widens treatment opportunity for Hurler syndrome, this examination of early treatment quantifies some ERT benefit, supports presumptions about BBB impenetrability, and aligns with current guidelines to treat with HCT.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison

Eisengart

Rudser

Xue

et al. 2018

Genetics in Medicine

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“…Due to strong evidence that earlier intervention leads to more favorable outcomes in MPS I [ 1 – 3 , 6 ], it was added to the Recommended Uniform Screening Panel (RUSP) for newborn screening. However, it is accepted that currently approved therapies are not perfect, and that people with MPS IH experience significant persisting disease burden [ 1 , 2 , 20 , 23 , 27 – 29 ]. This foundation of research and the addition of MPS I to the RUSP have energized the proliferation of new therapies for MPS I, many of which are currently in trial.…”

Section: Discussionmentioning

confidence: 99%

Beneath the floor: re-analysis of neurodevelopmental outcomes in untreated Hurler syndrome

Shapiro

Whitley

Eisengart

2018

Orphanet J Rare Dis

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BackgroundHurler syndrome (MPS IH), the severe, neurodegenerative form of type one mucopolysaccharidosis, is associated with rapid neurocognitive decline during toddlerhood and multi-system dysfunction. It is now standardly treated with hematopoietic cell transplantation (HCT), which halts accumulating disease pathology and prevents early death. While norm-based data on developmental functioning in untreated children have previously demonstrated neurocognitive decline, advances in methodology for understanding the cognitive functioning of children with neurodegenerative diseases have highlighted that the previous choice of scores to report results was not ideal. Specifically, the lowest possible norm-based score is 50, which obscures the complete range of cognitive functioning at more advanced stages of neurodeterioration. To a set of cognitive data collected on a sample of untreated children, we applied a modern method of score analysis, calculating a developmental quotient based on age equivalent scores, to reveal the full range of cognitive functioning beneath this cutoff of 50, uncovering new information about the rapidity of decline and the profound impairment in these children.ResultsAmong 39 observations for 32 patients with untreated Hurler syndrome, the full array of cognitive functioning below 50 includes many children in the severely to profoundly impaired range. The loss of skills per time unit was 14 points between age 1 and 2. There was a very large range of developmental quotients corresponding to the norm-based cutoff of 50.ConclusionsThis report enables clarification of functioning at levels that extend beneath the floor of 50 in previous work. At the dawn of newborn screening and amidst a proliferation of new therapies for MPS I, these data can provide crucial benchmark information for developing treatments, particularly for areas of the world where transplant may not be available.

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Niemann Peak Disease Type A in Necropsy of the Liver of a Four-Month-Old Female with Fe-ver and Pancytopenia

2021

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Leukodystrophies and Lysosomal Storage Disorders

Cited by 3 publications

References 408 publications

Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison

Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison

Beneath the floor: re-analysis of neurodevelopmental outcomes in untreated Hurler syndrome

Niemann Peak Disease Type A in Necropsy of the Liver of a Four-Month-Old Female with Fe-ver and Pancytopenia

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