Development of Clinical Pathways for Early Diagnosis and Management of SCID, SMA, and XLA Through Newborn Screening in Malaysia
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Published on: July 5, 2022
Alia Zainudin1,2, Thin Thin Aye3, Chloe Chen Sze Yun3
1Department of Pediatrics, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia.
Insights
Early newborn screening (NBS) for rare genetic disorders like Severe Combined Immunodeficiency (SCID), Spinal Muscular Atrophy (SMA), and X-Linked Agammaglobulinemia (XLA) is crucial. Establishing standardized clinical pathways in Malaysia can improve diagnosis and patient outcomes.
Area of Science:
- Medical Genetics
- Pediatric Immunology
- Public Health
Background:
- Severe Combined Immunodeficiency (SCID), Spinal Muscular Atrophy (SMA), and X-Linked Agammaglobulinemia (XLA) are critical infant genetic disorders with high morbidity and mortality if not diagnosed early.
- Advances in newborn screening (NBS) enable pre-symptomatic detection, facilitating life-saving interventions.
- Malaysia faces challenges with delayed diagnoses due to the lack of a standardized national clinical pathway.
Purpose of the Study:
- To review and synthesize evidence on clinical pathways for early diagnosis and management of SCID, SMA, and XLA in Malaysia.
- To emphasize diagnostic workflows, screening technologies, and healthcare system challenges.
- To propose a structured diagnostic framework to improve NBS and patient outcomes.
Main Methods:
- Review of current evidence on SCID, SMA, and XLA diagnosis and management.
- Examination of the Malaysian NBS landscape, including multiplex real-time PCR assays for TREC, KREC, and SMN1 gene deletion detection from dried blood spots (DBS).
- Analysis of disease epidemiology and consequences of delayed diagnosis.
Main Results:
- Current NBS practices and technologies like multiplex real-time PCR are outlined.
- The Screening for Health, Intervention, Nurturing of Every Child (SHINE) program's role in improving early diagnosis is discussed.
- Operational barriers and laboratory referral system coordination are identified as key challenges.
Conclusions:
- Expanding NBS programs and implementing a structured diagnostic framework are essential for improving early diagnosis.
- Addressing operational barriers and coordinating laboratory referrals can significantly enhance long-term outcomes for infants with SCID, SMA, and XLA in Malaysia.
- A proposed diagnostic framework incorporates screening interpretation, confirmatory testing, and urgency-based referral pathways.
Abstract:
Severe Combined Immunodeficiency (SCID), Spinal Muscular Atrophy (SMA), and X-Linked Agammaglobulinemia (XLA) are rare but life-threatening genetic disorders in infants that can lead to severe infections, progressive neuromuscular degeneration, or severe immune dysfunction associated with significant morbidity and mortality if not diagnosed early. Advances in newborn screening (NBS) technologies have enabled pre-symptomatic detection of these conditions, allowing early initiation of life-saving interventions such as hematopoietic stem cell transplantation, gene therapy, and immunoglobulin replacement therapy. However, the absence of a standardized national clinical pathway linking screening, confirmatory testing, and specialist referral in Malaysia continues to contribute to delayed diagnosis and suboptimal patient outcomes. This review examines and synthesizes current evidence on the clinical pathways for early diagnosis and management of SCID, SMA, and XLA, with particular emphasis on diagnostic workflows, screening technologies, and healthcare system challenges within the Malaysian context. The review examines disease epidemiology, consequences of delayed diagnosis, and the role of expanded NBS under the Screening for Health, Intervention, Nurturing of Every Child (SHINE) program in improving early diagnosis and management. In addition, the paper outlines the current NBS landscape, the use of multiplex real-time polymerase chain reaction (PCR) assays for simultaneous detection of T-cell receptor excision circles (TREC), kappa-deleting recombination excision circles (KREC), and survival motor neuron 1 (SMN1) gene deletion of exon 7 from dried blood spot (DBS) samples. A structured diagnostic framework incorporating screening interpretation, confirmatory testing, and urgency-based referral pathways is also proposed. By addressing current operational barriers and coordinating laboratory referral systems, expanding NBS programs could significantly improve early diagnosis and long-term outcomes for infants affected by SCID, SMA, and XLA in Malaysia.