NEONATAL SCID & SMA Screening qPCR FLEX
Multiplex real-time qPCR for the simultaneous screening of SCID and SMA from a single DBS.

Three targets are co-amplified in a single multiplex reaction, each read on a spectrally distinct channel: TREC (Texas Red/ROX), SMN1 (HEX/VIC) and the endogenous control RPP30 (FAM). RPP30 confirms adequate DNA input and quality, and normalises the TREC signal to a semi-quantitative result expressed as TREC copies per 10⁵ white blood cells. A healthy or SMA-carrier sample produces SMN1 and RPP30 signals; a sample with homozygous loss of SMN1 produces the RPP30 signal only. A TREC value at or below the laboratory-defined cut-off flags a presumptive SCID-positive result.

About SMA

The management of anterior spinal muscular atrophy (SMA) in newborns has evolved significantly over the last few years. Therefore, implementation of a spinal muscular atrophy screening program in newborns has quickly become medical-economic evidence in many countries.

Spinal muscular atrophy is a rare neuromuscular disease characterized by progressive muscle weakness caused by premature loss of anterior motor neurons of the spinal cord and brainstem nuclei.

The disease is associated, in almost 95% of cases, with a homozygous deletion of exon 7 of the SMN1 gene, a gene located on chromosome 5 (5q12.2-q13.3). This deletion hinders SMN protein synthesis, which is essential for survival of motor neurons. Approximately 5% of patients with SMA carry a heterozygous deletion of exon 7 from SMN1 combined with a point mutation in the second allele (i.e., Composite heterozygous).

The clinical severity of SMA is closely linked to the presence of a second gene, SMN2. This pseudogene, having more than 99% homology with the SMN1 gene, only produces approximately 10% functional SMN protein. The phenotype of SMA patients is thus found to be less severe and more slowly evolving as the number of copies of the SMN2 gene is high.

About SCID

Severe Combined Immunodeficiency (SCID) is a group of rare and life-threatening genetic disorders that results from mutations in different genes involved in the development and function of the immune system. These genetic defects impair the production and function of T-cells, B-cells, or both, leading to a severely compromised immune response. Infants with SCID may appear healthy at birth, but their immune system is highly vulnerable to severe and recurrent infections. Without early diagnosis and treatment, these infections can quickly escalate, leading to life-threatening complications.

SCID is typically caused by mutations in key genes such as IL2RG, ADA, RAG1, RAG2, and others, which play critical roles in the immune system’s development. In most cases, the condition is characterized by a complete or near-complete absence of functional T-cells, and sometimes B-cells, leaving affected individuals with little to no ability to mount an effective immune response.

If left untreated, SCID can be fatal within the first year or two of life. However, with prompt and appropriate treatment, outcomes can significantly improve. The most effective treatment options for SCID include:

• Bone Marrow Transplantation (BMT): This is the gold-standard treatment, where healthy blood-forming stem cells from a matched donor are transplanted into the patient to restore the immune system.
• Gene Therapy: An emerging and promising alternative, where corrective genes are introduced into the patient’s own cells to help restore immune function.
• Enzyme Replacement Therapy (ERT): Sometimes used for specific forms of SCID, depending on the underlying genetic cause.

Newborn screening for SCID has become increasingly widespread, allowing early detection of the disorder and enabling timely treatment to prevent life-threatening infections. Early diagnosis through newborn screening programs plays a critical role in improving outcomes and saving lives.