Open issues in Mucopolysaccharidosis type I-Hurler

Rossella Parini, Federica Deodato, Maja Di Rocco, Edoardo Lanino, Franco Locatelli, Chiara Messina, Attilio Rovelli, Maurizio Scarpa

Research output: Contribution to journalReview article

Abstract

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 follow-up 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.

Original languageEnglish
Article number112
JournalOrphanet Journal of Rare Diseases
Volume12
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Mucopolysaccharidosis I
Hematopoietic Stem Cell Transplantation
Transplants
Iduronidase
Newborn Infant
Enzyme Replacement Therapy
Inborn Genetic Diseases
Age Factors
Metabolic Diseases
Airway Obstruction
Therapeutics
Child Development
Cardiomyopathies
Patient Selection
Signs and Symptoms
Primary Health Care
Referral and Consultation
Biomarkers
Tissue Donors
Parturition

Keywords

  • Allogeneic hematopoietic stem cell transplantation
  • Enzyme replacement therapy
  • Hurler
  • Lysosomal storage
  • Metabolic disorder
  • Mucopolysaccharidosis I

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

Open issues in Mucopolysaccharidosis type I-Hurler. / Parini, Rossella; Deodato, Federica; Di Rocco, Maja; Lanino, Edoardo; Locatelli, Franco; Messina, Chiara; Rovelli, Attilio; Scarpa, Maurizio.

In: Orphanet Journal of Rare Diseases, Vol. 12, No. 1, 112, 01.01.2017.

Research output: Contribution to journalReview article

Parini, Rossella ; Deodato, Federica ; Di Rocco, Maja ; Lanino, Edoardo ; Locatelli, Franco ; Messina, Chiara ; Rovelli, Attilio ; Scarpa, Maurizio. / Open issues in Mucopolysaccharidosis type I-Hurler. In: Orphanet Journal of Rare Diseases. 2017 ; Vol. 12, No. 1.
@article{10d27542ed644bb5910debeeaa8b59fe,
title = "Open issues in Mucopolysaccharidosis type I-Hurler",
abstract = "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 follow-up 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.",
keywords = "Allogeneic hematopoietic stem cell transplantation, Enzyme replacement therapy, Hurler, Lysosomal storage, Metabolic disorder, Mucopolysaccharidosis I",
author = "Rossella Parini and Federica Deodato and {Di Rocco}, Maja and Edoardo Lanino and Franco Locatelli and Chiara Messina and Attilio Rovelli and Maurizio Scarpa",
year = "2017",
month = "1",
day = "1",
doi = "10.1186/s13023-017-0662-9",
language = "English",
volume = "12",
journal = "Orphanet Journal of Rare Diseases",
issn = "1750-1172",
publisher = "BioMed Central Ltd.",
number = "1",

}

TY - JOUR

T1 - Open issues in Mucopolysaccharidosis type I-Hurler

AU - Parini, Rossella

AU - Deodato, Federica

AU - Di Rocco, Maja

AU - Lanino, Edoardo

AU - Locatelli, Franco

AU - Messina, Chiara

AU - Rovelli, Attilio

AU - Scarpa, Maurizio

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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 follow-up 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.

AB - 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 follow-up 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.

KW - Allogeneic hematopoietic stem cell transplantation

KW - Enzyme replacement therapy

KW - Hurler

KW - Lysosomal storage

KW - Metabolic disorder

KW - Mucopolysaccharidosis I

UR - http://www.scopus.com/inward/record.url?scp=85027834118&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027834118&partnerID=8YFLogxK

U2 - 10.1186/s13023-017-0662-9

DO - 10.1186/s13023-017-0662-9

M3 - Review article

AN - SCOPUS:85027834118

VL - 12

JO - Orphanet Journal of Rare Diseases

JF - Orphanet Journal of Rare Diseases

SN - 1750-1172

IS - 1

M1 - 112

ER -