Initial screening of SMA in high-risk Thai pediatric patients: DBS PCR-based testing with Multiplex Ligation-dependent Probe Amplification confirmation
Keywords:
Spinal muscular atrophy (SMA), initial diagnostic screening, dried blood spot (DBS), Multiplex Ligation-Dependent Probe Amplification (MLPA)Abstract
Background: Spinal muscular atrophy (SMA) is a rare neuromuscular disorder commonly found in children, leading to progressive muscle weakness. Although gene therapy is now available, delays in diagnosis and treatment initiation still occur due to cost constraints, lengthy testing processes, and limited accessibility. These delays can result in treatment outcomes that are below expectations.
Objectives: To report the turnaround time of an initial screening test for SMA using a dried blood spot (DBS) PCR-based method and Multiplex Ligation-Dependent Probe Amplification (MLPA) in high-risk pediatric patients.
Methods: This cross-sectional descriptive study included pediatric patients from newborns with at least 34 weeks of gestational age to adolescents 21 years old who were considered at high risk for SMA. Participants were recruited from Siriraj Hospital and various affiliated hospitals under Thailand's Ministry of Public Health. Blood samples were screened using the DBS PCR-based method, and MLPA was performed to confirm the diagnosis.
Results: Fifty patients (21 males, 29 females) were included. Of these, 8 were diagnosed with SMA using the DBS method. All patients were subsequently confirmed by MLPA, with complete concordance between the two methods. The median turnaround time from analysis to reporting using the DBS method was 2 days (range: 1–30 days), while it was 14 days (range: 1–20 days) for MLPA, (p value 0.001). By the DBS method, three patients were identified as SMA type 1, four as type 2, and one as type 3.
Conclusions: Initial SMA screening using the DBS PCR-based method provided a significantly shorter turnaround time than MLPA. This approach may be a suitable alternative for improving diagnostic efficiency and expediting access to timely treatment.
Downloads
References
Swoboda KJ, Prior TW, Scott CB, McNaught TP, Wride MC, Reyna SP, et al. Natural history of denervation in SMA: Relation to age, SMN2 copy number, and function. Ann Neurol. 2005;57:704-12.
Ramdas S, Servais L. New treatments in spinal muscular atrophy: An overview of currently available data. Expert Opin Pharmacother. 2020;21:307-15.
Govoni A, Gagliardi D, Comi GP, Corti S. Time is motor neuron: Therapeutic window and its correlation with pathogenetic mechanisms in spinal muscular atrophy. Mol Neurobiol. 2018;55:6307-18.
Baranello G, Darras BT, Day JW, Deconinck N, Klein A, Masson R, et al. Risdiplam in type 1 spinal muscular atrophy. N Engl J Med. 2021;384:915-23.
Mercuri E, Baranello G, Boespflug-Tanguy O, De Waele L, Goemans N, Kirschner J, et al. Risdiplam in types 2 and 3 spinal muscular atrophy: A randomised, placebo-controlled, dose-finding trial followed by 24 months of treatment. Eur J Neurol. 2023;30:1945-56.
National Statistical Office Thailand [Internet].2022 [cited 2022 Mar 3]. Available from: http://nso.go.th.
Chien YH, Chiang SC, Weng WC, Lee NC, Lin CJ, Hsieh WS, et al. Presymptomatic diagnosis of spinal muscular atrophy through newborn screening. J Pediatr. 2017;190:124-9.e1.
Boemer F, Caberg JH, Dideberg V, Dardenne D, Bours V, Hiligsmann M, et al. Newborn screening for SMA in Southern Belgium. Neuromuscul Disord. 2019;29:343-9.
Lin Y, Lin CH, Yin X, Zhu L, Yang J, Shen Y, et al. Newborn Screening for spinal muscular atrophy in China using DNA mass spectrometry. Front Genet. 2019;10:1255.
Shinohara M, Niba ETE, Wijaya YOS, Takayama I, Mitsuishi C, Kumasaka S, et al. A novel system for spinal muscular atrophy screening in newborns: Japanese pilot study. Int J Neonatal Screen. 2019;5:41.
Vill K, Kölbel H, Schwartz O, Blaschek A, Olgemöller B, Harms E, et al. One year of newborn screening for SMA - results of a german pilot project. J Neuromuscul Dis. 2019;6:503-15.
Czibere L, Burggraf S, Fleige T, Glück B, Keitel LM, Landt O, et al. High-throughput genetic newborn screening for spinal muscular atrophy by rapid nucleic acid extraction from dried blood spots and 384-well qPCR. Eur J Hum Genet. 2020;28:23-30.
Mailman MD, Heinz JW, Papp AC, Snyder PJ, Sedra MS, Wirth B, et al. Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med. 2002;4:20-6.
Sakpichaisakul K, Katanyuwong K, Intusoma U, Paprad T, Suwanpakdee P, Khongkhatithum C, et al. Spinal muscular atrophy in an upper-middle-income nation before the advent of reimbursed disease-modifying therapies. BMJ Paediatrics Open. 2024;8:e002775.
de Souza Godinho FM, Bock H, Gheno TC, Saraiva-Pereira ML. Molecular analysis of spinal muscular atrophy: A genotyping protocol based on TaqMan(®) real-time PCR. Genet Mol Biol. 2012;35:955-9.
Prior TW, Snyder PJ, Rink BD, Pearl DK, Pyatt RE, Mihal DC, et al. Newborn and carrier screening for spinal muscular atrophy. Am J Med Genet A. 2010;152:1608-16.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 The Royal College of Pediatricians Of Thailand
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
