One Year of Newborn Screening for SMA – Results of a German Pilot Project

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

Infants Diagnosed with Spinal Muscular Atrophy and 4 SMN2 Copies through Newborn Screening – Opportunity or Burden?1

“…The screening procedure has already been published in a previous manuscript, presenting the clinical and electrophysiological outcome after one year of newborn screening for SMA [24]. In short, the screening was performed in two federal states of Germany, Bavaria and North Rhine Westphalia, starting in January 2018.…”

“…Since a number of SMN-dependent and SMNindependent therapies are available [11], the timing of treatment is crucial for a good outcome [12,13] and available data show that presymptomatic treatment is superior to treatment after onset of symptoms [14] experts agree that newborn screening should be established [15,[16][17][18][19][20][21][22][23]. Currently first pilot projects for a genetic NBS in SMA are underway [18,[24][25][26][27][28]. It has been shown that children with less than 4 SMN2 copies clearly have a benefit from an early presymptomatic treatment [14,24].…”

“…Currently first pilot projects for a genetic NBS in SMA are underway [18,[24][25][26][27][28]. It has been shown that children with less than 4 SMN2 copies clearly have a benefit from an early presymptomatic treatment [14,24].…”

Newborn Screening for SMA - Results After Two Years of a Large Pilot Project 

“…The NBS procedure has been published in a previous manuscript 15 . In short, screening was performed in two federal states of Germany, starting in January 2018.…”

The Impact of the CFTR Gene Discovery on Cystic Fibrosis Diagnosis, Counseling, and Preventive Therapy

“…The data analysis software was designed to mask much of the sequence data and reveal only the predetermined CF-causing variants in the CFTR gene as characterized by the CFTR2 project [48,49]. The significance of this study includes: (1) it was the first report from a public health NBS laboratory regarding the technical feasibility of applying NGS in routine NBS practice; and (2) the reported laboratory-developed DNA isolation method in this study is applicable to other molecular testing currently used in public health NBS laboratories, such as multiplexing real-time PCR assays to screen for severe combined immunodeficiency (SCID) [50] and spinal muscular atrophy (SMA) [51,52].…”