New-Born Screening for Spinal Muscular Atrophy: Results of a Latvian Pilot Study

Linda Gailite,Jekaterina Isakova,Signe Setlere,Ieva Micule,Madara Auzenbaha,Olga Sterna,Aleksejs Isakovs,Mikus Diriks,Maija Konika

doi:10.3390/ijns8010015

Abstract

New disease-modifying treatments have recently been approved for 5q spinal muscular atrophy (SMA) and early treatment has been associated with a better clinical outcome. Accordingly, new-born screening (NBS) for SMA should be implemented to ensure early diagnosis of affected individuals. The aim of this study was to determine the feasibility and usefulness of NBS for SMA in Latvia. Between February and November of 2021, 10,411 parents consented to participation in the study. DNA testing for the SMN1 exon 7 homozygous deletion was conducted using qPCR with fluorescent locked nucleic acid primers. In the first month of testing, reporting of results took up to a maximum of 17 days after samples arrived in the laboratory. However, following familiarisation with the procedure, the median report time was reduced to 11 days after birth. Forty cases required samples to be taken again due to poor quality of the isolated DNA transpiring from either the quality of the blood punch or manual mistakes during DNA isolation. The SMN1 exon 7 homozygous deletion was identified in two individuals, which was subsequently confirmed by multiplex ligation-dependent probe amplification. When a NBS sample is taken 48 to 72 h after birth and transported to the laboratory within two working days after collection according to legal requirements, DNA test results can be reported to healthcare professionals before the 12th day of life. Expansion of our SMA 5q NBS procedure to the whole of Latvia is feasible and would facilitate early diagnosis and result in more effective treatment. We strongly advocate that SMA is added to the national Latvia Recommended Uniform Screening Panel.

Highlights

Introduction published maps and institutional affilThe term spinal muscular atrophy (SMA) applies to a diverse group of genetic disorders that affect the spinal motor neuron
There are no precise data regarding the frequency of SMA 5q in Latvia
Following the procurement of dried blood spot (DBS) samples and consent to national new-born screening (NBS) whilst in hospital, parents of new-borns were subsequently contacted by telephone and offered the opportunity to participate in the pilot programme for SMA screening

Summary

Introduction

Introduction published maps and institutional affilThe term spinal muscular atrophy (SMA) applies to a diverse group of genetic disorders that affect the spinal motor neuron. The most common SMA type is caused by pathogenic variants in the SMN1 (survival of motor neuron 1) gene located on the long arm of chromosome 5 (SMA 5q). It is the leading cause of infant mortality from a single gene disorder [1], with an incidence ranging from 1 in 10,000 to 1 in 6000 new-borns (1–1.67:10,000). There are no precise data regarding the frequency of SMA 5q in Latvia. An analysis of the 10-year period between 2007 and 2017 reported that 26 individuals were diagnosed with SMA in Latvia, resulting in an incidence of 1:9091 [4].

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