Progression of Hip Dysplasia in Mucopolysaccharidosis Type I Hurler After Successful Hematopoietic Stem Cell Transplantation

Langereis, Eveline J.; Os, Matthijs M. den; Breen, Catherine; Jones, Simon A.; Knaven, O.C.; Mercer, Jean; Miller, Weston P.; Kelly, Paula M.; Kennedy, Jim; Ketterl, Tyler G.; O’Meara, Anne; Orchard, Paul J.; Lund, Troy C.; Rijn, Rick R. van; Sakkers, R. J. B.; White, Klane K.; Wijburg, Frits A.

doi:10.2106/jbjs.o.00601

Cited by 27 publications

(28 citation statements)

References 26 publications

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“…In MPS I, the medical treatment (ERT as well as bone marrow transplant [BMT]) does not modifies the natural history of the skeletal deformities [12] , [13] . In MPS I, II or VI, apart when the treatment is administered in the very first weeks of life, ERT or BMT can improve the joint mobility through decreasing the infiltration of GAGs into ligaments, tendons, joint capsules, and other soft tissues; these treatments, however, never influence the outcome of bone morphology [14] , [15] , [16] .…”

Section: Discussionmentioning

confidence: 99%

30 months follow-up of an early enzyme replacement therapy in a severe Morquio A patient: About one case

Cao¹,

Wiedemann²,

Quinaux³

et al. 2016

Molecular Genetics and Metabolism Reports

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Patients under 5 years were not evaluated in the phase-3 study for enzyme replacement therapy (ERT) in MPS IV A. Here we describe the evolution of a severe Morquio A pediatric patient who was diagnosed at 19 months old and treated by ERT at 21 months old for the next 30 months.Applying the standard ERT protocol on this very young patient appeared to reduce his urinary excretion of glycosaminoglycans (GAGs); the improvements in both the 6 minute-walk test (6MWT) and the stair climb test, however, were no different than those reported in the nature history study. Additionally, this young patient experienced many ERT-associated side effects, and as a result a specific corticosteroid protocol (1 mg/kg of betamethasone the day before and 1 h before the ERT infusion) was given to avoid adverse events. Under these treatments, the height of this patient increased during the first year of the ERT although no more height gain was observed thereafter for 18 months. However, despite of ERT, his bone deformities (including severe pectus carinatum) actually worsened and his medullar cervical spine compression showed no improvement (thus needed decompression surgery).Conclusion: early ERT treatment did not improve the bone outcome in this severe MPS IV A patient after the 30 months-long treatment. A longer term follow up is required to further assess the efficacy of ERT on both the motor and the respiratory function of the patient.

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Section: Discussionmentioning

confidence: 99%

30 months follow-up of an early enzyme replacement therapy in a severe Morquio A patient: About one case

Cao¹,

Wiedemann²,

Quinaux³

et al. 2016

Molecular Genetics and Metabolism Reports

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“…Although isolated DDH can be diagnosed in healthy individuals, there are cases when extensive genetic mutations cause teratologic or syndromic DDH [2,3], which occurs prenatally. In syndromic types, DDH can be a part of many or only a sole manifestation of skeletal dysplasia [4][5][6], or it may be present in conjunction with other malformations, e.g., pes equinovarus and acetabular labrum abnormalities. Syndromic dysplasia exists also in association with different pathologies such as Down's syndrome and neurogenic [7], renal or cardiovascular abnormalities.…”

Section: Introductionmentioning

confidence: 99%

Developmental Dysplasia of the Hip: A Review of Etiopathogenesis, Risk Factors, and Genetic Aspects

Harsanyi¹,

Zamborský²,

Krajčíová³

et al. 2020

Medicina

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As one of the most frequent skeletal anomalies, developmental dysplasia of the hip (DDH) is characterized by a considerable range of pathology, from minor laxity of ligaments in the hip joint to complete luxation. Multifactorial etiology, of which the candidate genes have been studied the most, poses a challenge in understanding this disorder. Candidate gene association studies (CGASs) along with genome-wide association studies (GWASs) and genome-wide linkage analyses (GWLAs) have found numerous genes and loci with susceptible DDH association. Studies put major importance on candidate genes associated with the formation of connective tissue (COL1A1), osteogenesis (PAPPA2, GDF5), chondrogenesis (UQCC1, ASPN) and cell growth, proliferation and differentiation (TGFB1). Recent studies show that epigenetic factors, such as DNA methylation affect gene expression and therefore could play an important role in DDH pathogenesis. This paper reviews all existing risk factors affecting DDH incidence, along with candidate genes associated with genetic or epigenetic etiology of DDH in various studies.

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“…On the other hand, a recent evaluation of radiographic parameters in 52 patients with MPS I-H demonstrated progressive hip dysplasia over time, despite successful HSCT being performed at a median age of 12 months (range 3–30 months) [26]. …”

Section: Introductionmentioning

confidence: 99%

“…An accurate digitally scored radiographic assessment was used to validate a correlation between radiographic parameters and clinical progression of hip dysplasia [26]. Lower enzyme activity was correlated with poor development of the craniocervical junction, due to dens hypoplasia, in a retrospective study of MPS I-H patients who underwent HSCT [25].…”

Section: Introductionmentioning

confidence: 99%

Open issues in Mucopolysaccharidosis type I-Hurler

Parini

Deodato

Rocco

et al. 2017

Orphanet J Rare Dis

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Mucopolysaccharidosis I-Hurler (MPS I-H) is the most severe form of a metabolic genetic disease caused by mutations of IDUA gene encoding the lysosomal α-L-iduronidase enzyme. MPS I-H is a rare, life-threatening disease, evolving in multisystem morbidity including progressive neurological disease, upper airway obstruction, skeletal deformity and cardiomyopathy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the gold standard for the treatment of MPS I-H in patients diagnosed and treated before 2-2.5 years of age, having a high rate of success. Beyond the child's age, other factors influence the probability of treatment success, including the selection of patients, of graft source and the donor type employed. Enzyme replacement therapy (ERT) with human recombinant laronidase has also been demonstrated to be effective in ameliorating the clinical conditions of pre-transplant MPS I-H patients and in improving HSCT outcome, by peri-transplant co-administration. Nevertheless the long-term clinical outcome even after successful HSCT varies considerably, with a persisting residual disease burden. Other strategies must then be considered to improve the outcome of these patients: one is to pursue early pre-symptomatic diagnosis through newborn screening and another one is the identification of novel treatments. In this perspective, even though newborn screening can be envisaged as a future attractive perspective, presently the best path to be pursued embraces an improved awareness of signs and symptoms of the disorder by primary care providers and pediatricians, in order for the patients' timely referral to a qualified reference center. Furthermore, sensitive new biochemical markers must be identified to better define the clinical severity of the disease at birth, to support clinical judgement during the follow-up and to compare the effects of the different therapies. A prolonged neuropsychological follow-up of post-transplant cognitive development of children and residual disease burden is needed. In this perspective, the reference center must guarantee a multidisciplinary followup with an expert team. Diagnostic and interventional protocols of reference centers should be standardized whenever possible to allow comparison of clinical data and evaluation of results. This review will focus on all these critical issues related to the management of MPS I-H.

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Progression of Hip Dysplasia in Mucopolysaccharidosis Type I Hurler After Successful Hematopoietic Stem Cell Transplantation

Cited by 27 publications

References 26 publications

30 months follow-up of an early enzyme replacement therapy in a severe Morquio A patient: About one case

30 months follow-up of an early enzyme replacement therapy in a severe Morquio A patient: About one case

Developmental Dysplasia of the Hip: A Review of Etiopathogenesis, Risk Factors, and Genetic Aspects

Open issues in Mucopolysaccharidosis type I-Hurler

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