Factors associated with delayed diagnosis of spinal muscular atrophy in China and changes in diagnostic delay

Cao, Yanyan; Cheng, Miaomiao; Qu, Yue; Bai, Jianling; Peng, Xiaoyin; Ge, Xiushan; Jin, Yue; Wang, Hong; Song, Fang

doi:10.1016/j.nmd.2021.03.002

Cited by 10 publications

(8 citation statements)

References 14 publications

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“…Delayed diagnosis is a common problem relating to SMA and other rare diseases. Cao et al [ 47 ] reported that the diagnostic window for SMA types 1–3 with SMN1 homozygous deletion was 3.38, 4.08, and 11.37 months, respectively, in China, and found that the main factors influencing the time of diagnosis were the SMA type and clinical diagnosis at the first visit. In our study, case 1 presented with disease onset at 4 months old and was finally diagnosed as type 1c SMA at 22 months old, while case 3 presented with possible SMA manifestation at birth but was subsequently diagnosed with NEM2 at the age of 6 years and 9 months.…”

Section: Discussionmentioning

confidence: 99%

Variants located in intron 6 of SMN1 lead to misdiagnosis in genetic detection and screening for SMA

Qu,

Bai,

Jiao

et al. 2024

Heliyon

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Section: Discussionmentioning

confidence: 99%

Variants located in intron 6 of SMN1 lead to misdiagnosis in genetic detection and screening for SMA

Qu,

Bai,

Jiao

et al. 2024

Heliyon

Self Cite

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“…The development of standards of care for children with SMA had to some degree changed the natural history. However, the situation of compliance standards of care in the SMA population of China is still unsatisfactory ( 29 ). A pilot study comparing a natural group of SMA 1 patients with a palliative group with health care in China pointed out that active health management improves the survival rate of SMA patients, reduces the incidence of complications, and improves the prognosis of patients ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive profile and natural history of pediatric patients with spinal muscular atrophy: A large retrospective study from China

Li²,

Shi³

et al. 2022

Front. Neurol.

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BackgroundThere is a large population of people with spinal muscular atrophy (SMA) in China, and new disease-modifying therapies have become available recently. However, comprehensive data on the management and profile of treatment-naive SMA patients in China are still lacking.MethodsAs a retrospective study, a large cohort of treatment-naive patients with clinical and genetic diagnoses of 5q SMA were enrolled, ranging from neonatal to 18 years old, from the Neurology Department of Children's Hospital of Fudan University between January 2013 and December 2020. The data regarding their clinical presentations, genetic defects, motor function assessment results, and follow ups were reviewed.ResultsWe enrolled 392 SMA patients (male: female = 189: 203): 1a = 46, 1b = 44, 1c = 31, 2a = 119, 2b = 56, 3a = 52, 3b = 14, from 27 of the 34 administrative districts in China, and 389 patients harbored homozygous deletion of exon 7 in the SMN1 gene (99.2%). The median age of onset was 0.08 (range: 0–0.30), 0.25 (0.06–0.60), 0.42 (0.08–1.50), 0.67 (0.07–5.08), 1.0 (0.40–1.83), 1.5 (1.00–3.00), and 4.04 (1.80–12.00) years old for SMA 1a, 1b, 1c, 2a, 2b, 3a, and 3b patients, while the median age of first assessment was 0.25 (0.08–2.60), 0.42 (0.17–1.90), 0.80 (0.17–4.5), 2.50 (0.5–15.83), 2.92 (1.08–13.42), 4.25 (1.58–17.33), and 7.34 (3.67–14.00) years old, respectively. Patients were followed up with for up to 15.8 years. The median event-free survival time was 7 months, 15 months, and indeterminate in SMA 1a, 1b, and 1c patients (p < 0.0001), with a better survival situation for higher SMN2 copies (p = 0.0171). The median age of sitting loss was 5.75 years and 13.5 years in SMA 2a and 2b (p = 0.0214) and that of ambulation loss was 9.0 years and undefined in SMA 3a and 3b (p = 0.0072). Cox regression analysis showed that higher SMN2 copies indicated better remaining ambulation in SMA 3. The median time to develop orthopedic deformities was 4.5, 5.2, and 10.1 years in SMAs 1c, 2, and 3, respectively (p < 0.0001), with a possible trend of better preservation of joint function for patients under regular rehabilitation (p = 0.8668).ConclusionOur study elucidated insight into the comprehensive management and profile of different types of SMA patients in China, providing a clinical basis for assessing the efficacy of new therapies.

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“…Diagnosis of SMA may become more difficult after the neonatal period. Milder symptoms can make a diagnosis of SMA more difficult because of similarities with other muscle weakness diseases [24,30].…”

Section: Expansion Of Sma Screening To Older Children or Adultsmentioning

confidence: 99%

“…Even though NBS-SMA has begun in many countries, there remain many older children or adults with SMA in the population who were not detected in early infancy. The majority of them may be diagnosed with SMA in a timely fashion, but the rest may be diagnosed late or may not be diagnosed, particularly those with a later onset of the disease [22][23][24][25]. Undiagnosed patients cannot access treatment with the new drugs.…”

Section: Introductionmentioning

confidence: 99%

Detection of Spinal Muscular Atrophy Patients Using Dried Saliva Spots

Wijaya

Nishio

Niba

et al. 2021

Genes

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Spinal muscular atrophy (SMA) is a lower motor neuron disease, once considered incurable. The main symptoms are muscle weakness and muscular atrophy. More than 90% of cases of SMA are caused by homozygous deletion of survival motor neuron 1 (SMN1). Emerging treatments, such as splicing modulation of SMN2 and SMN gene replacement therapy, have improved the prognoses and motor functions of patients. However, confirmed diagnosis by SMN1 testing is often delayed, suggesting the presence of diagnosis-delayed or undiagnosed cases. To enable patients to access the right treatments, a screening system for SMA is essential. Even so, the current newborn screening system using dried blood spots is still invasive and cumbersome. Here, we developed a completely non-invasive screening system using dried saliva spots (DSS) as an alternative DNA source to detect SMN1 deletion. In this study, 60 DSS (40 SMA patients and 20 controls) were tested. The combination of modified competitive oligonucleotide priming-polymerase chain reaction and melting peak analysis clearly distinguished DSS samples with and without SMN1. In conclusion, these results suggest that our system with DSS is applicable to SMA patient detection in the real world.

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Factors associated with delayed diagnosis of spinal muscular atrophy in China and changes in diagnostic delay

Cited by 10 publications

References 14 publications

Variants located in intron 6 of SMN1 lead to misdiagnosis in genetic detection and screening for SMA

Variants located in intron 6 of SMN1 lead to misdiagnosis in genetic detection and screening for SMA

Comprehensive profile and natural history of pediatric patients with spinal muscular atrophy: A large retrospective study from China

Detection of Spinal Muscular Atrophy Patients Using Dried Saliva Spots

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