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One Year of Newborn Screening for SMA - Results of a German Pilot Project.
J Neuromuscul Dis 2019; 6(4):503-515JN

Abstract

OBJECTIVE

Spinal muscular atrophy (SMA) is the most common neurodegenerative disease in childhood. The study was conducted to assess the impact of early detection of SMA by newborn screening (NBS) on the clinical course of the disease.

METHODS

Screening was performed in two federal states of Germany, Bavaria and North Rhine Westphalia, between January 2018 and February 2019. The incidence in the screening population was calculated as number of detected patients with a homozygous deletion in the SMN1-gene per number of screened patients. To get an idea about the incidence of newly diagnosed SMA in the year prior to screening a survey covering all neuropediatric centers in the state of Bavaria was conducted, identifying all SMA-cases in 2017 and 2018. Following positive NBS and confirmatory diagnostic test, treatment was advised according to the recommendations of the "American SMA NBS Multidisciplinary Working Group". Immediate treatment with Nusinersen was recommended in children with 2 and 3 SMN2 copies and a conservative strict follow-up strategy in children with ≥4 copies. All children underwent regular standardized neuropediatric examination, CHOP INTEND and HINE-2 testing as well as electrophysiological exams every 2-3 months.

RESULTS

165,525 children were screened. 22 cases of SMA were identified, meaning an incidence rate of 1:7524. SMN2 copy number analysis showed 2 SMN2 copies in 45% of patients, 3 SMN2 copies in 19 % and 4 SMN2 copies in 36%. These findings are confirmed in the most recent statistical data-cut from 31st August 2019 (incidence 1:7089, 2 SMN2 copies in 44%, 3 in 15% and 4 in 38%). Comparison with up-to-date German data on SMA incidence and the Bavarian survey give evidence that NBS did not lead to a relevant increase in incidence. 10 patients with 2 or 3 SMN2 copies were treated with Nusinersen, starting between 15- 39 days after birth, in 7/10 patients before onset of symptoms. Presymptomatically treated patients (age at last examination: 1- 12 months, median 8 months) showed no muscle weakness by the age of one month to one year. One child with 4 SMN2 copies became symptomatic at the age of 8 months.

CONCLUSIONS

Newborn screening, resulting in presymptomatic treatment, improves outcome in children with genetically proven SMA. Newborn screening for SMA should be introduced in all countries where therapy is available. An immediate therapy in cases with 4 SMN2 copies should be considered.

Authors+Show Affiliations

Department of Pediatric Neurology and Developmental Medicine, Dr. v. Hauner Children's Hospital, LMU - University of Munich, Munich, Germany.Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University of Essen, Germany.Department of Pediatric Neurology, Muenster University Hospital, Münster, Germany.Department of Pediatric Neurology and Developmental Medicine, Dr. v. Hauner Children's Hospital, LMU - University of Munich, Munich, Germany.Previously Labor Becker, Olgemöller & Kollegen, Munich, Germany.Department of Pediatric Medicine, Previously Muenster University Hospital, Münster, Germany.Labor Becker & Kollegen, Munich, Germany.Labor Becker & Kollegen, Munich, Germany.Labor Becker & Kollegen, Munich, Germany.Genetikum®, Center for Human Genetics, Neu-Ulm, Germany.Screening Center of the Bavarian Health and Food Safety Authority, Oberschleissheim, Germany.Institute of Human Genetics, University of Cologne, Cologne, Germany.Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, University of Essen, Germany.Department of Pediatric Neurology, Muenster University Hospital, Münster, Germany.Labor Becker & Kollegen, Munich, Germany.RoMed Klinikum Rosenheim, Department of Pedriatric Nephrology, Rosenheim, Germany.Department of Pediatric Neurology and Developmental Medicine, Dr. v. Hauner Children's Hospital, LMU - University of Munich, Munich, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31594245

Citation

Vill, Katharina, et al. "One Year of Newborn Screening for SMA - Results of a German Pilot Project." Journal of Neuromuscular Diseases, vol. 6, no. 4, 2019, pp. 503-515.
Vill K, Kölbel H, Schwartz O, et al. One Year of Newborn Screening for SMA - Results of a German Pilot Project. J Neuromuscul Dis. 2019;6(4):503-515.
Vill, K., Kölbel, H., Schwartz, O., Blaschek, A., Olgemöller, B., Harms, E., ... Müller-Felber, W. (2019). One Year of Newborn Screening for SMA - Results of a German Pilot Project. Journal of Neuromuscular Diseases, 6(4), pp. 503-515. doi:10.3233/JND-190428.
Vill K, et al. One Year of Newborn Screening for SMA - Results of a German Pilot Project. J Neuromuscul Dis. 2019;6(4):503-515. PubMed PMID: 31594245.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - One Year of Newborn Screening for SMA - Results of a German Pilot Project. AU - Vill,Katharina, AU - Kölbel,Heike, AU - Schwartz,Oliver, AU - Blaschek,Astrid, AU - Olgemöller,Bernhard, AU - Harms,Erik, AU - Burggraf,Siegfried, AU - Röschinger,Wulf, AU - Durner,Jürgen, AU - Gläser,Dieter, AU - Nennstiel,Uta, AU - Wirth,Brunhilde, AU - Schara,Ulrike, AU - Jensen,Beate, AU - Becker,Marc, AU - Hohenfellner,Katharina, AU - Müller-Felber,Wolfgang, PY - 2019/10/9/pubmed PY - 2019/10/9/medline PY - 2019/10/10/entrez KW - Nusinersen KW - SMA treatment KW - Spinal muscular atrophy KW - newborn screening KW - prognosis SP - 503 EP - 515 JF - Journal of neuromuscular diseases JO - J Neuromuscul Dis VL - 6 IS - 4 N2 - OBJECTIVE: Spinal muscular atrophy (SMA) is the most common neurodegenerative disease in childhood. The study was conducted to assess the impact of early detection of SMA by newborn screening (NBS) on the clinical course of the disease. METHODS: Screening was performed in two federal states of Germany, Bavaria and North Rhine Westphalia, between January 2018 and February 2019. The incidence in the screening population was calculated as number of detected patients with a homozygous deletion in the SMN1-gene per number of screened patients. To get an idea about the incidence of newly diagnosed SMA in the year prior to screening a survey covering all neuropediatric centers in the state of Bavaria was conducted, identifying all SMA-cases in 2017 and 2018. Following positive NBS and confirmatory diagnostic test, treatment was advised according to the recommendations of the "American SMA NBS Multidisciplinary Working Group". Immediate treatment with Nusinersen was recommended in children with 2 and 3 SMN2 copies and a conservative strict follow-up strategy in children with ≥4 copies. All children underwent regular standardized neuropediatric examination, CHOP INTEND and HINE-2 testing as well as electrophysiological exams every 2-3 months. RESULTS: 165,525 children were screened. 22 cases of SMA were identified, meaning an incidence rate of 1:7524. SMN2 copy number analysis showed 2 SMN2 copies in 45% of patients, 3 SMN2 copies in 19 % and 4 SMN2 copies in 36%. These findings are confirmed in the most recent statistical data-cut from 31st August 2019 (incidence 1:7089, 2 SMN2 copies in 44%, 3 in 15% and 4 in 38%). Comparison with up-to-date German data on SMA incidence and the Bavarian survey give evidence that NBS did not lead to a relevant increase in incidence. 10 patients with 2 or 3 SMN2 copies were treated with Nusinersen, starting between 15- 39 days after birth, in 7/10 patients before onset of symptoms. Presymptomatically treated patients (age at last examination: 1- 12 months, median 8 months) showed no muscle weakness by the age of one month to one year. One child with 4 SMN2 copies became symptomatic at the age of 8 months. CONCLUSIONS: Newborn screening, resulting in presymptomatic treatment, improves outcome in children with genetically proven SMA. Newborn screening for SMA should be introduced in all countries where therapy is available. An immediate therapy in cases with 4 SMN2 copies should be considered. SN - 2214-3602 UR - https://www.unboundmedicine.com/medline/citation/31594245/One_Year_of_Newborn_Screening_for_SMA_-_Results_of_a_German_Pilot_Project L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JND-190428 DB - PRIME DP - Unbound Medicine ER -