Abstract
IntroductionSpinal muscular atrophy (SMA) is caused by a defect in the survival motor neuron 1 (SMN1) gene. The Cooperative Study of the natural history of SMA Type I in Taiwan is a retrospective, longitudinal, observational study that helps in further understanding SMA disease progression in patients who have not received disease-modifying therapeutic interventions. MethodsCase report forms were used to collect demographics; genetic confirmation; SMN2 copy number; treatment patterns; and clinical outcomes including ventilator use, endotracheal tube intubation, tracheostomy, gastrostomy, complications, and survival. ResultsA total of 111 patients with SMA Type I were identified over the study period (1979–2015). Mean (median) age of onset and age at confirmed diagnosis were 1.3 (0.8) and 4.9 (4.4) months, respectively. SMN1 deletion/mutation was documented in 70 patients and SMN2 copy number in 32 (2 copies, n = 20; 3 copies, n = 12). At 240 months, survival probability for patients born during 1995–2015 versus 1979–1994 was significantly longer (p = 0.0057). Patients with 3 SMN2 copies showed substantially longer 240-month survival versus patients with 2 SMN2 copies. Over the 36-year period, mean (median) age at death was 31.9 (8.8) months. As of December 2015, 95 patients had died, 13 were alive, and 3 were lost to follow-up. The use of supportive measures (tracheostomy and gastrostomy) was associated with improved survival. ConclusionsThese data describe the short survival of patients with SMA Type I in Taiwan in the pretreatment era, emphasizing the positive impact of supportive measures on survival.
Highlights
Spinal muscular atrophy (SMA) is caused by a defect in the survival motor neuron 1 (SMN1) gene
SMN1 gene deletion or mutation was confirmed in 63.1% (70/111) of patients with SMA Type I; only 28.8% of patients (32/111) had a documented SMN2 copy number
Despite earlier improvements in palliative care in Taiwan, these natural history data demonstrate the high mortality rate, short survival, and delayed diagnosis of SMA Type I, highlighting the need for SMA newborn screening. These results show improved survival of patients with SMA Type I in Taiwan since 1995, when ventilator and nutritional support were made widely available following the commencement of national health insurance
Summary
Spinal muscular atrophy (SMA) is caused by a defect in the survival motor neuron 1 (SMN1) gene. Patients with SMA Type I have a median survival of 7.4 months (3– 56 months), with the age of onset being reported as a predictive factor of survival [9]. The onset of SMA Type II is between 6 and 18 months of age; the highest motor milestone achieved is sitting independently (termed ‘‘sitters”), and patients have a life expectancy to early adulthood [3,9]. Patients with SMA Type III and Type IV typically show onset from 18 months of age (‘‘walkers”) and adulthood, respectively, and show survival into adulthood, with normal life span in SMA Type IV [3,8,9]
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