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Page 2 of 10 Tãtaru et al. Rare Dis Orphan Drugs J 2024;3:19 https://dx.doi.org/10.20517/rdodj.2024.08

INTRODUCTION
Across countries, newborn screening (NBS) is implemented heterogeneously, with significant variations
between high- and low-middle-income countries. A study published by Novartis and Charles River
Associates (CRA) in March 2022 showed that one heel prick test can potentially diagnose up to 50 diseases,
as demonstrated by Italy, which ranks as the first country in the European Union (EU) where NBS is
currently implemented for 48 diseases (or more, depending on the region), while Cyprus and Romania
[1]
perform NBS for only two diseases . The efficiency of the diagnostic pathway remains a critical step in the
management of SMA, and the inclusion of SMA in the national NBS programs, with adequate follow-up
and genetic counseling, facilitates earlier treatment access and care. Across Europe, several countries have
already included SMA in their national screening programs, among them Belgium, Germany, Netherlands,
and Poland, while others developed pilots and provided an efficient reimbursement system for access to
diagnostic resources (Austria, Czech Republic, Denmark, Finland, France, Italy, North Macedonia, Spain,
Sweden, and the United Kingdom) .
[2,3]
Spinal Muscular Atrophy (SMA) is a genetic recessive disease caused by the mutation or absence of the
Survival Motor Neuron 1 (SMN1) gene located in the q region of chromosome 5, often referred to as 5q
SMA, which results in motor neuron degeneration and thus progressive muscle paralysis. In recent years,
new treatments have been shown to significantly improve the motor function of symptomatic patients, but
do not enable them to regain normal motor activity. In adults, they stabilize or even slightly reverse the
course of the disease. Their effectiveness is largely dependent on the age of the patient and his or her ability
to renew motor neurons, but above all, on the level of degeneration of the nervous system . Three effective
[4]
treatments have received regulatory approval from the European Medicines Agency (EMA) and at least one
of them is now available for infants in some European countries . Disease severity is a continuum;
[5]
however, to facilitate the standard of care, the disease forms were classified by type (type 0 to 4) based on
the age of disease onset . The age at which a child first exhibits symptoms is a reliable predictor of the
[6]
progression of the disease in terms of motor functions and associated disabilities if left untreated [Table 1].

For patients diagnosed through a genetic test of 5q13 SMA, a double deletion of the SMN1 gene will
indicate a positive result. SMN1 and SMN2 have identical sequences except for a single nucleotide change in
exon 7 of SMN2 which alters splicing. SMN2 usually produces a small amount of functional protein and the
copy number of SMN2 typically influences the severity of SMA disease .
[4]

• 1 copy of SMN2: the child will develop a severe form of type 1 and will probably show clinical signs from
birth;

• 2 copies of SMN2: the child will present the first symptoms at a very young age and will probably have
SMA type 1 or 2;

• 3 copies of SMN2: first symptoms develop in childhood, and the patient will probably have SMA type 2 or
3;

• 4 copies of SMN2: the first symptoms will appear in adolescence or adulthood, and the patient will
probably develop a type 3 or 4 SMA;

• Beyond 5 copies is quite rare, the patient can develop SMA type 4, and many adults diagnosed in this way
[5]
are usually asymptomatic .