Spinal muscular atrophy (SMA) is a group of disorders caused by the degeneration of the motor neuron cells of the anterior horn of the spinal cord and, in some subtypes, of the bulbar motor neurons. Almost all cases are genetically determined. Most SMAs are autosomal recessive diseases, caused by homozygous deletions of the survival motor neuron (SMN) gene located on the long arm of chromosome 5. The estimated incidence of recessive childhood and juvenile SMA linked to deletion of the SMN gene is 1 in 6000 to 10000 live births, with a carrier frequency of 1 in 35 in the general population, making it a major genetic cause of infant mortality. Up to 95-97% of all childhood cases are due to homozygous deletions of the survival motor neuron 1 (SMN1) gene, or telomeric SMN, located on chromosome 5q11.2-13.3. The remaining 3-5% of cases are due to small mutations in SMN1 (rather than complete deletions). Until a few years ago, the prognosis of type 1 SMA was poor. In the absence of therapies, the only measures were supportive (ventilation, nutrition) and the prospect, especially in the early forms, was to accompany them towards an early end of life. There are currently three treatment options available: nusinersen, risdiplam, and gene therapy with onasemnogene abeparvovec. The three options were found to be equally effective in reducing the symptoms of the disease, making it possible to reach or safeguard fundamental stages in a child's neuromotor development, starting from the ability to remain seated. At this moment, gene therapy is probably the preferred choice. To date, in Italy, there are approximately 100 patients undergoing gene therapy. To ensure maximum benefit for affected patients, it is essential that the therapy is administered as soon as possible. Literature shows how the administration of gene therapy in pre-symptomatic subjects made it possible to achieve a better neurological outcome compared to symptomatic patients. From this perspective, the inclusion of spinal muscular atrophy in neonatal screening is of fundamental relevance.
Study Type
OBSERVATIONAL
Enrollment
11,500
Drops of blood from a puncture from the newborn's heel are collected, dried for 24 hours at room temperature and then sent to the laboratory for analysis. The screening test is a first-level molecular genetic test that allows the identification of patients affected by SMA who present the homozygous deletion of exon 7 of the SMN1 gene using the Real Time polymerase chain reaction (PCR) technique. This qualitative method is based on the use of specific fluorescent probes that discriminate the SMN1 gene from its survival motor neuron 2 (SMN2) homologue and also allow the quality assessment of genomic DNA through amplification of an internal control gene. When a positive testing patient is identified, the birth center is promptly notified to call the family and carry out a further blood sample aimed at confirming the possible diagnosis with a second level test.
SC Pediatria Gorizia - Monfalcone
Monfalcone, Gorizia, Italy
RECRUITINGInstitute for Maternal and Child Health - IRCCS "Burlo Garofolo"
Trieste, Italy
RECRUITINGRate of newborn screened
Number of newborns screened per 100 live births
Time frame: In the first 48-72 hours after birth
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.