Incomplete biomarker response in mucopolysaccharidosis type I after successful hematopoietic cell transplantation

Kuiper, Gé Ann; Hasselt, Peter M. van; Boelens, Jaap Jan; Wijburg, Frits A.; Langereis, Eveline J.

doi:10.1016/j.ymgme.2017.05.009

Cited by 4 publications

(2 citation statements)

References 29 publications

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“…Total urinary GAG levels were within normal ranges in all patients (except in one). However, there were abnormal fractions of heparan and dermatan sulfate present as reported by others [52], and serum IDUA levels were below normal ranges in the majority of patients despite total chimerism. It should be noted that serum IDUA activity takes years to normalize.…”

Section: Discussionsupporting

confidence: 67%

Long term disease burden post-transplantation: three decades of observations in 25 Hurler patients successfully treated with hematopoietic stem cell transplantation (HSCT)

Guffon

Pettazzoni

Pangaud

et al. 2021

Orphanet J Rare Dis

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Background Mucopolysaccharidosis type I-Hurler syndrome (MPSI-H) is a lysosomal storage disease characterized by severe physical symptoms and cognitive decline. Early treatment with hematopoietic cell transplant (HSCT) is critical to the survival of these patients. While survival rates and short-term outcomes are known to be improved by HSCT, the long-term cognitive, adaptive and psychosocial functional outcomes of children with (MPSI-H) post-HSCT are not well documented. This manuscript focuses on retrospective long-term follow-up (7–33 years) of 25 MPSI-H patients, transplanted between 1986 and 2011. Results The median age at transplantation was 21 months (range 12–57 months). Except for one death, all successfully transplanted MPSI-H patients surviving at least 1 year after HSCT are alive to-date, with a median age of 21 years (range 8–36 years) at the last follow-up evaluation. A majority of HSCT grafts were bone marrow transplants (BMT), resulting in durable full chimerism in 18 (72%). Pre-HSCT, the onset of first symptoms occurred very early, at a median age of 3 months (range birth-16 months). The most prevalent symptoms before MPSI-H diagnosis involved progressive dysostosis multiplex; almost all patients suffered from hip dysplasia and thoracolumbar spine Kyphosis. Despite HSCT, considerable residual disease burden and ensuing corrective surgical interventions were observed in all, and at every decade of follow-up post HSCT. Late-onset psychiatric manifestations were significant (n = 17 patients; 68%), including depression in 13 patients at a median onset age of 18 years (range 13–31 years), hyperactivity and attention deficit disorder (n = 4), and multiple acute psychotic episodes (APE), independent of depression observed (n = 3) at a median onset age of 18 years (range 17–31 years). The adult Welscher Intelligence Scale results (n = 16) were heterogenous across the four scale dimensions; overall lower scores were observed on both working memory index (median WMI = 69.5) and processing speed index (median PSI = 65), whereas verbal comprehension index (median VCI = 79) and perceptual reasoning index (median PRI = 74) were higher. Conclusion With advanced treatment options, MPSI-H are living into 3rd and 4th decades of life, however not disease free and with poor adaptation. Residual disease (loss of mobility, limited gross and fine motor skills; low cognitive ability; suboptimal cardiopulmonary function, vision and hearing) negatively impacts the quality of life and psychosocial functioning of affected individuals.

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Section: Discussionsupporting

confidence: 67%

Long term disease burden post-transplantation: three decades of observations in 25 Hurler patients successfully treated with hematopoietic stem cell transplantation (HSCT)

Guffon

Pettazzoni

Pangaud

et al. 2021

Orphanet J Rare Dis

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“…HSCT is considered the primary treatment for MPS IH and can increase the life span of patients, especially at below two years of age and prior to the onset of cognitive impairment [ 140 , 141 , 142 ]. HSCT decreases HS and DS concentrations in the blood and urine [ 143 ], but CSF HS concentrations after HSCT have not been evaluated. However, post-HSCT intrathecal ERT with a recombinant iduronidase decreases CSF HS concentrations in patients with MPS IH, and the percent decrease in a certain species of HS was positively associated with the percent change in IQ score from baseline to two years, indicating a link between the treatment response of CSF HS and neurocognitive outcomes in MPS IH [ 132 ].…”

Section: Hs As a Biomarker For Mpssmentioning

confidence: 99%

Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses

Minami

Morimoto

Morioka

et al. 2022

IJMS

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Heparan sulfate (HS) is an essential glycosaminoglycan (GAG) as a component of proteoglycans, which are present on the cell surface and in the extracellular matrix. HS-containing proteoglycans not only function as structural constituents of the basal lamina but also play versatile roles in various physiological processes, including cell signaling and organ development. Thus, inherited mutations of genes associated with the biosynthesis or degradation of HS can cause various diseases, particularly those involving the bones and central nervous system (CNS). Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders involving GAG accumulation throughout the body caused by a deficiency of GAG-degrading enzymes. GAGs are stored differently in different types of MPSs. Particularly, HS deposition is observed in patients with MPS types I, II, III, and VII, all which involve progressive neuropathy with multiple CNS system symptoms. While therapies are available for certain symptoms in some types of MPSs, significant unmet medical needs remain, such as neurocognitive impairment. This review presents recent knowledge on the pathophysiological roles of HS focusing on the pathogenesis of MPSs. We also discuss the possible use and significance of HS as a biomarker for disease severity and therapeutic response in MPSs.

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Incidence of Bloodstream Infections after Hematopoietic Stem Cell Transplantation for Hurler Syndrome

Dunseath,

O’Connor,

Mahulkar

et al. 2023

Transplantation and Cellular Therapy

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Incomplete biomarker response in mucopolysaccharidosis type I after successful hematopoietic cell transplantation

Cited by 4 publications

References 29 publications

Long term disease burden post-transplantation: three decades of observations in 25 Hurler patients successfully treated with hematopoietic stem cell transplantation (HSCT)

Long term disease burden post-transplantation: three decades of observations in 25 Hurler patients successfully treated with hematopoietic stem cell transplantation (HSCT)

Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses

Incidence of Bloodstream Infections after Hematopoietic Stem Cell Transplantation for Hurler Syndrome

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