The Clinical Outcome of Hurler Syndrome after Stem Cell Transplantation

Abstract

Hurler syndrome (HS) is a severe inborn error of metabolism causing progressive multi-system morbidity and death in early childhood. At present, stem cell transplantation (SCT) is the only available treatment that can prevent central nervous system disease progression in HS patients. Although SCT has been shown to be effective for several important clinical outcome parameters, the reported clinical outcome after successful SCT is variable among HS patients and there are still some major limitations. This review will focus on the clinical outcome of HS patients after successful SCT, with particular emphasis on the long-term outcome and complications. In addition, factors that are suggested to contribute to the variable outcome are outlined, as well as the limitations of SCT in HS patients.

Long-Term Cognitive and Functional Outcomes in Children with Mucopolysaccharidosis (MPS)-IH (Hurler Syndrome) Treated with Hematopoietic Cell Transplantation

“…These studies suggest that, when performed early enough in the disease process, HCT improved or stabilized neurocognitive development and adaptive skills in most children, particularly in combination with enzyme replacement therapy, preventing progressive deterioration (Malm et al 2008;Bjoraker et al 2006;Eisengart et al 2013). Nonetheless, the neurocognitive and adaptive outcomes after HCT for Hurler syndrome are highly variable (Aldenhoven et al 2008). Several factors are suspected to play a role in this heterogeneity, including genotype, age at transplantation, graft source, and demographic factors, but their relative contributions have been incompletely studied (Grewal et al 2003;Prasad and Kurtzberg 2010;Peters et al 1998).…”

Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and Hurler syndrome

“…There is consensus about the efficacy of HSCT when performed early in life for MPS-IH 9,13,14 and at early stages in CALD 6,7,12,15 . Case reports suggested that HSCT might reduce demyelination in juvenile (onset between two and 14 years) and adult forms of MLD when performed as early as possible 3,4,5,16 .…”

Long-Term Functional Outcomes of Children with Hurler Syndrome Treated with Unrelated Umbilical Cord Blood Transplantation

“…Insufficient enzyme delivery to poorly vascularized tissues is thought to account for musculoskeletal deterioration after transplantation, similar to that of untreated children (Weisstein et al 2004;Aldenhoven 2008). Although HSCT may improve ventricular hypertrophy and ventricular function, cardiac valve disease persists , and hearing impairment, persistent corneal clouding, and noninfectious pulmonary complications (e.g., diffuse alveolar hemorrhage, idiopathic pneumonia syndrome) after transplantation are also common (Souillet et al 2003;Kharbanda et al 2006).…”

“…Since enzyme replacement therapy (ERT) is not capable of crossing the blood-brain barrier, HSC transplantation is the treatment of choice for Hurler syndrome. Clinical outcomes include reversal of organomegaly, preservation of neurocognitive development, and improved hearing, vision, and cardiopulmonary function in most transplanted patients (Guffon et al 1998;Whitley et al 1993;Shapiro et al 1995;Peters et al 1996;Vellodi et al 1997;Peters et al 1998;Souillet et al 2003;Aldenhoven et al 2008;Malm et al 2008). However, outcomes are highly variable, and manifestations in certain organ systems continue to progress.…”