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Newborn Screening for Spinal Muscular Atrophy: Ontario Testing and Follow-up Recommendations

Published online by Cambridge University Press:  16 October 2020

Hugh J. McMillan
Affiliation:
Children’s Hospital of Eastern Ontario Research Institute, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
Kristin D. Kernohan
Affiliation:
Children’s Hospital of Eastern Ontario Research Institute, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada Newborn Screening Ontario, Ottawa, Ontario, Canada
Ed Yeh
Affiliation:
Children’s Hospital of Eastern Ontario Research Institute, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada Newborn Screening Ontario, Ottawa, Ontario, Canada
Kim Amburgey
Affiliation:
Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
Jennifer Boyd
Affiliation:
Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
Craig Campbell
Affiliation:
Children’s Hospital Western Ontario, Department of Pediatrics, Epidemiology and Clinical Neurological Sciences, Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada
James J. Dowling
Affiliation:
Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
Hernan Gonorazky
Affiliation:
Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
Janet Marcadier
Affiliation:
Newborn Screening Ontario, Ottawa, Ontario, Canada
Mark A. Tarnopolsky
Affiliation:
McMaster Children’s Hospital, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
Jiri Vajsar
Affiliation:
Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
Alex MacKenzie
Affiliation:
Children’s Hospital of Eastern Ontario Research Institute, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
Pranesh Chakraborty
Affiliation:
Children’s Hospital of Eastern Ontario Research Institute, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada Newborn Screening Ontario, Ottawa, Ontario, Canada
Corresponding

Abstract:

Background:

Spinal muscular atrophy (SMA) is characterized by the progressive loss of motor neurons causing muscle atrophy and weakness. Nusinersen, the first effective SMA therapy was approved by Health Canada in June 2017 and has been added to the provincial formulary of all but one Canadian province. Access to this effective therapy has triggered the inclusion of SMA in an increasing number of Newborn Screening (NBS) programs. However, the range of disease-modifying SMN2 gene copy numbers encountered in survival motor neuron 1 (SMN1)-null individuals means that neither screen-positive definition nor resulting treatment decisions can be determined by SMN1 genotype alone. We outline an approach to this challenge, one that specifically addresses the case of SMA newborns with four copies of SMN2.

Objectives:

To develop a standardized post-referral evaluation pathway for babies with a positive SMA NBS screen result.

Methods:

An SMA NBS pilot trial in Ontario using first-tier MassARRAY and second-tier multi-ligand probe amplification (MLPA) was launched in January 2020. Prior to this, Ontario pediatric neuromuscular disease and NBS experts met to review the evidence regarding the diagnosis and treatment of children with SMA as it pertained to NBS. A post-referral evaluation algorithm was developed, outlining timelines for patient retrieval and management.

Conclusions:

Ontario’s pilot NBS program has created a standardized path to facilitate early diagnosis of SMA and initiation of treatment. The goal is to provide timely access to those SMA infants in need of therapy to optimize motor function and prolong survival.

Résumé :

RÉSUMÉ :

Dépistage de l’amyotrophie spinale chez le nouveau-né : recommandations sur le dépistage et le suivi de la maladie en Ontario.

Contexte :

L’amyotrophie spinale (AS) se caractérise par une perte progressive des neurones moteurs, ce qui entraîne une atrophie et une faiblesse musculaires. Nusinersen, le premier traitement efficace de l’AS a été approuvé par Santé Canada en juin 2017, et ajouté à la liste des médicaments assurés dans toutes les provinces, sauf dans une seule. L’arrivée de ce traitement efficace a eu pour effet d’ajouter l’AS dans un nombre croissant de programmes de dépistage néonatal (PDN). Toutefois, comme le nombre de copies du gène SMN2 chez les personnes « nulles » à l’égard de SMN1 est modifié par plus d’une maladie, ni la définition d’un test de dépistage positif ni les décisions relatives au traitement qui en découle ne peuvent reposer sur le seul génotype SMN1. Aussi avons-nous élaboré une démarche qui vise spécifiquement l’AS à 4 copies du gène SMN2 chez le nouveau-né (N.-N.).

Objectif :

L’étude visait à tracer le chemin à suivre après la consultation pour l’évaluation des N.-N. ayant obtenu un résultat positif au dépistage de l’AS dans le cadre du PDN.

Méthode :

Un essai pilote de dépistage néonatal de l’AS réalisé à l’aide de MassARRAY au premier tour et de l’amplification multiplex de sondes dépendant d’une ligation (MLPA) au second tour été lancé en Ontario, en janvier 2020. Auparavant, des spécialistes des maladies neuromusculaires chez les enfants et des experts du PDN en Ontario se sont rencontrés afin d’examiner les données probantes sur le diagnostic et le traitement de l’AS chez les enfants, dans le cadre du PDN. A suivi l’élaboration d’un algorithme d’évaluation après consultation, qui établissait les différentes étapes à suivre en vue de l’aiguillage du patient et de la prise en charge de la maladie.

Conclusion :

Le programme pilote de dépistage néonatal de l’Ontario a permis d’uniformiser la démarche à suivre et ainsi de faciliter la pose précoce du diagnostic d’AS et l’instauration du traitement. Il a pour but le repérage rapide des nourrissons atteints d’AS qui ont besoin de traitement afin d’optimiser le fonctionnement moteur et de prolonger la survie.

Type
Original Article
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press on behalf of The Canadian Journal of Neurological Sciences Inc.

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Footnotes

*

Both authors contributed equally to this work.

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