Diagnostic journey in Spinal Muscular Atrophy: Is it still an odyssey?

Abstract

Background The advent of new therapies has increased the need to achieve early diagnosis in Spinal Muscular Atrophy (SMA). The aim of the present study was to define the age of diagnosis in the three main types of SMA with pediatric-onset and the timing between the recognition of clinical signs and confirmed genetic diagnosis. Methods All patients with a confirmed diagnosis of type I, II, III SMA followed in 5 Italian centers were included in this study, assessing age at symptoms onset, presenting sign or symptom, age at diagnosis, interval between clinical onset and diagnosis and type of medical investigations conducted in order to obtain the diagnosis. Results The cohort included 480 patients, 191 affected by SMA type I, 210 by type II and 79 by type III. The mean age at diagnosis was 4.70 months (SD ±2.82) in type I, 15.6 months (SD ±5.88) in type II, and 4.34 years (SD±4.01) in type III. The mean time between symptom onset and diagnosis was 1.94 months (SD±1.84) in type I, 5.28 months (SD±4.68) in type II and 16.8 months (SD±18.72) in type III. Conclusions Our results suggest that despite improved care recommendations there is still a marked diagnostic delay, especially in type III. At the time new therapies are becoming available

New Treatments in Spinal Muscular Atrophy: Positive Results and New Challenges

“…This is a consequence of the rapid denervation process occurring in the first six months of life and the aim of pre-symptomatic treatment is the precocious rescue of motoneurons. However, we recently demonstrated that the mean age at diagnosis is 4.70 months (SD ± 2.82) in SMA type I, 15.6 months (SD ± 5.88) in SMA type II, and 4.34 years (SD ± 4.01) in SMA type III [ 73 ]. Therefore, these findings support the need of NBS to achieve a better efficacy of the available therapeutic options.…”

Clinical Variability in Spinal Muscular Atrophy Type III

“…2 The clinical subtypes, based on age of onset and maximum motor function achieved, range from the most severe SMA type I to the mildest SMA type IV. 3 SMA has a cumulative incidence of 1 in 11,000 live births. 4 However, the epidemiologic burden of SMA is not equally divided over the subtypes.…”

“…The disease is caused by mutations in the survival motor neuron 1 ( SMN1 ) gene 2 . The clinical subtypes, based on age of onset and maximum motor function achieved, range from the most severe SMA type I to the mildest SMA type IV 3 …”

Newborn Screening for SMA - Results After Two Years of a Large Pilot Project 

“…Notably, there were manifestations of reduced muscle strength in the legs or CMAPs < 1 mV (N. ulnaris), which at this time would have been missed on a routine examination. NBS avoided a diagnostic delay which otherwise still is the rule 25,26 . Since SMN expression is highest prenatally 5 , it is reasonable that motor neuron death already occurs to some extent before birth.…”