International working group identifies need for newborn screening for mucopolysaccharidosis type I but states that existing hurdles must be overcome

Parini, Rossella; Broomfield, Alexander; Cleary, Maureen; Meırleır, Linda De; Rocco, Maja Di; Fathalla, Waseem; Guffon, Nathalie; Lampe, Christina; Lund, Allan M.; Scarpa, Maurizio; Tylki‐Szymańska, Anna; Zeman, Jiří

doi:10.1111/apa.14587

Cited by 14 publications

(12 citation statements)

References 49 publications

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“…Newborn screening (NBS) focuses on the early identification of disorders to allow early intervention avoiding irreversible life-threatening manifestations [110]. It is very clear that MPS I patients have great benefit from early treatment, justifying its inclusion in the NBS programs [1,52,60,62,111,112].…”

Section: Newborn Screeningmentioning

confidence: 99%

Mucopolysaccharidosis Type I

et al. 2020

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Mucopolysaccharidosis type I (MPS I) is caused by the deficiency of α-l-iduronidase, leading to the storage of dermatan and heparan sulfate. There is a broad phenotypical spectrum with the presence or absence of neurological impairment. The classical form is known as Hurler syndrome, the intermediate form as Hurler–Scheie, and the most attenuated form is known as Scheie syndrome. Phenotype seems to be largely influenced by genotype. Patients usually develop several somatic symptoms such as abdominal hernias, extensive dermal melanocytosis, thoracolumbar kyphosis odontoid dysplasia, arthropathy, coxa valga and genu valgum, coarse facial features, respiratory and cardiac impairment. The diagnosis is based on the quantification of α-l-iduronidase coupled with glycosaminoglycan analysis and gene sequencing. Guidelines for treatment recommend hematopoietic stem cell transplantation for young Hurler patients (usually at less than 30 months of age). Intravenous enzyme replacement is approved and is the standard of care for attenuated—Hurler–Scheie and Scheie—forms (without cognitive impairment) and for the late-diagnosed severe—Hurler—cases. Intrathecal enzyme replacement therapy is under evaluation, but it seems to be safe and effective. Other therapeutic approaches such as gene therapy, gene editing, stop codon read through, and therapy with small molecules are under development. Newborn screening is now allowing the early identification of MPS I patients, who can then be treated within their first days of life, potentially leading to a dramatic change in the disease’s progression. Supportive care is very important to improve quality of life and might include several surgeries throughout the life course.

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Section: Newborn Screeningmentioning

confidence: 99%

Mucopolysaccharidosis Type I

et al. 2020

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“…5,6 The recent initiation of newborn screening for MPS I as well as other programs to identify individuals with MPS I at an age when CNS and somatic involvement may be minimal, highlight the need for accurate delineation of patients so effective therapies can be initiated early. [7][8][9][10][11][12] Unfortunately, no currently available biochemical assessments allow for accurate classification of patients as either severe or attenuated. 13 Published diagnosis and management guidelines suggest a role for IDUA genotype in management decision making.…”

Section: Introductionmentioning

confidence: 99%

Genotype‐phenotype relationships in mucopolysaccharidosis type I (MPS I): Insights from the International MPS I Registry

et al. 2019

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Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disorder resulting from pathogenic variants in the α‐L‐iduronidase (IDUA) gene. Clinical phenotypes range from severe (Hurler syndrome) to attenuated (Hurler‐Scheie and Scheie syndromes) and vary in age of onset, severity, and rate of progression. Defining the phenotype at diagnosis is essential for disease management. To date, no systematic analysis of genotype‐phenotype correlation in large MPS I cohorts have been performed. Understanding genotype‐phenotype is critical now that newborn screening for MPS I is being implemented. Data from 538 patients from the MPS I Registry (380 severe, 158 attenuated) who had 2 IDUA alleles identified were examined. In the 1076 alleles identified, 148 pathogenic variants were reported; of those, 75 were unique. Of the 538 genotypes, 147 (27%) were unique; 40% of patients with attenuated and 22% of patients with severe MPS I had unique genotypes. About 67.6% of severe patients had genotypes where both variants identified are predicted to severely disrupt protein/gene function and 96.1% of attenuated patients had at least one missense or intronic variant. This dataset illustrates a close genotype/phenotype correlation in MPS I but the presence of unique IDUA missense variants remains a challenge for disease prediction.

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“…Devant ces possibilités, de nombreux pays ont mis en place des programmes de DNN des MSL, notamment pour la maladie de Pompe 3 , la mucopolysaccharidose de type I (maladie de Hurler) 4 ou la maladie de Fabry 5 [21]. Néanmoins, le DNN de ces maladies reste controversé, principalement en raison de problèmes éthiques liés à l'hétérogénéité du retentissement symptomatique de ces maladies sur les patients, et aux incertitudes sur les bénéfices à long terme des traitements actuellement disponibles [22,23].…”

Section: Synthèseunclassified

Les principaux outils biologiques appliqués au dépistage néonatal

Cheillan

2021

Med Sci (Paris)

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Au cours des cinquante dernières années, le dépistage néonatal est devenu incontournable dans les programmes de santé publique de très nombreux pays. Durant toutes ces années, le nombre de maladies susceptibles d’être dépistées à la naissance n’a cessé de croître grâce aux possibilités offertes par les progrès techniques de la biologie clinique. Le test de Guthrie a permis la miniaturisation du prélèvement de sang, permettant ainsi le dépistage biologique dans la population des nouveau-nés. Par la suite, la fluorimétrie, l’immunoanalyse et, plus récemment, la spectrométrie de masse en tandem ont rendu possible le dépistage de nombreuses maladies qu’il est possible de traiter. Les nouvelles possibilités de séquençage du génome et d’intelligence artificielle vont probablement ouvrir une nouvelle ère, malgré les nombreuses questions éthiques qui se poseront. Cette revue propose de dresser le panorama des techniques biologiques utilisées actuellement pour le dépistage néonatal et de mettre en perspective la place de nouvelles évolutions techniques.

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International working group identifies need for newborn screening for mucopolysaccharidosis type I but states that existing hurdles must be overcome

Cited by 14 publications

References 49 publications

Mucopolysaccharidosis Type I

Mucopolysaccharidosis Type I

Genotype‐phenotype relationships in mucopolysaccharidosis type I (MPS I): Insights from the International MPS I Registry

Les principaux outils biologiques appliqués au dépistage néonatal

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