scholarly journals Diagnostic criteria for spinal muscular atrophy 5q

2021 ◽  
Vol 11 (3) ◽  
pp. 37-44
Author(s):  
I. V. Sharkova ◽  
E. L. Dadali ◽  
S. S. Nikitin
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Molecular Genetic ◽  
Signs And Symptoms ◽  
Type I ◽  
Diagnostic Significance ◽  
Disease Manifestation ◽  
Smn1 Gene ◽  
Before And After

Background. The variety of phenotypic manifestations of spinal muscular atrophy 5q (5qCMA) is the reason for the difficulty in diagnosing and delaying the diagnosis, which is of particular importance today due to the emergence of new etiopathogenetic therapeutic possibilities.Objective: determination of the main clinical features and symptoms of 5qCMA with onset at different age periods, and the development of an algorithm that can help in making decisions regarding the need for testing the SMN1 gene by primary care and hospital doctors.Materials and methods. A retrospective analysis of the case histories of patients observed at the Research Center of Medical Genetics with a confirmed diagnosis of 5qCMA was carried out.Results. The study included data from 315 patients, including: 173 with type I, 95 and 47 with types II and III 5qCMA. In all cases, the presence and diagnostic significance of 27 signs and symptoms were analyzed, depending on the age of disease manifestation. An attempt was made to isolate the main symptoms, which are the basis for the mandatory exclusion of 5qCMA by molecular genetic methods in patients with the onset of the disease before and after 18 months of life.

SMN1 gene point mutations in type I–IV proximal spinal muscular atrophy patients with a single copy of SMN1

2015 ◽  
Vol 51 (9) ◽  
pp. 925-931
Author(s):  
V. V. Zabnenkova ◽  
E. L. Dadali ◽  
S. B. Artemieva ◽  
I. V. Sharkova ◽  
G. E. Rudenskaya ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Point Mutations ◽  
Single Copy ◽  
Type I ◽  
Smn1 Gene ◽  
Proximal Spinal Muscular Atrophy

Hydrocephalus in Spinal Muscular Atrophy: A Case Report and Review of the Literature

2020 ◽  
Author(s):  
Jeetendra P. Sah ◽  
Aaron W. Abrams ◽  
Geetha Chari ◽  
Craig Linden ◽  
Yaacov Anziska
Keyword(s):  
Spinal Muscular Atrophy ◽  
Clinical Characteristics ◽  
Clinical Presentation ◽  
Muscular Atrophy ◽  
Communicating Hydrocephalus ◽  
Type I ◽  
Review Of The Literature ◽  
Radiographic Findings ◽  
Comprehensive Review ◽  
The Relationship

AbstractIn this article, we reported a case of spinal muscular atrophy (SMA) type I noted to have tetraventricular hydrocephalus with Blake's pouch cyst at 8 months of age following intrathecal nusinersen therapy. The association of hydrocephalus with SMA is rarely reported in the literature. Development of hydrocephalus after intrathecal nusinersen therapy is also reported in some cases, but a cause–effect relationship is not yet established. The aim of this study was to describe the clinical characteristics of a patient with SMA type I and hydrocephalus, to review similar cases reported in the literature, and to explore the relationship between nusinersen therapy and development of hydrocephalus. The clinical presentation and radiographic findings of the patient are described and a comprehensive review of the literature was conducted. The adverse effect of communicating hydrocephalus related to nusinersen therapy is being reported and the authors suggest carefully monitoring for features of hydrocephalus developing during the course of nusinersen therapy.

scholarly journals Spinal Muscular Atrophy after Nusinersen Therapy: Improved Physiology in Pediatric Patients with No Significant Change in Urine, Serum, and Liquor 1H-NMR Metabolomes in Comparison to an Age-Matched, Healthy Cohort

Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 206
Author(s):  
Leon Deutsch ◽  
Damjan Osredkar ◽  
Janez Plavec ◽  
Blaž Stres
Keyword(s):  
Machine Learning ◽  
Spinal Muscular Atrophy ◽  
1H Nmr ◽  
Pediatric Patients ◽  
Muscular Atrophy ◽  
Male And Female ◽  
Before And After ◽  
Healthy Cohort ◽  
Males And Females ◽  
Urine Serum

Spinal muscular atrophy (SMA) is a genetically heterogeneous group of rare neuromuscular diseases and was until recently the most common genetic cause of death in children. The effects of 2-month nusinersen therapy on urine, serum, and liquor 1H-NMR metabolomes in SMA males and females were not explored yet, especially not in comparison to the urine 1H-NMR metabolomes of matching male and female cohorts. In this prospective, single-centered study, urine, serum, and liquor samples were collected from 25 male and female pediatric patients with SMA before and after 2 months of nusinersen therapy and urine samples from a matching healthy cohort (n = 125). Nusinersen intrathecal application was the first therapy for the treatment of SMA by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Metabolomes were analyzed using targeted metabolomics utilizing 600 MHz 1H-NMR, parametric and nonparametric multivariate statistical analyses, machine learning, and modeling. Medical assessment before and after nusinersen therapy showed significant improvements of movement, posture, and strength according to various medical tests. No significant differences were found in metabolomes before and after nusinersen therapy in urine, serum, and liquor samples using an ensemble of statistical and machine learning approaches. In comparison to a healthy cohort, 1H-NMR metabolomes of SMA patients contained a reduced number and concentration of urine metabolites and differed significantly between males and females as well. Significantly larger data scatter was observed for SMA patients in comparison to matched healthy controls. Machine learning confirmed urinary creatinine as the most significant, distinguishing SMA patients from the healthy cohort. The positive effects of nusinersen therapy clearly preceded or took place devoid of significant rearrangements in the 1H-NMR metabolomic makeup of serum, urine, and liquor. Urine creatinine was successful at distinguishing SMA patients from the matched healthy cohort, which is a simple systemic novelty linking creatinine and SMA to the physiology of inactivity and diabetes, and it facilitates the monitoring of SMA disease in pediatric patients through non-invasive urine collection.

scholarly journals Predictive fat mass equations for spinal muscular atrophy type I children: Development and internal validation

2021 ◽  
Vol 40 (4) ◽  
pp. 1578-1587
Author(s):  
Andrea Foppiani ◽  
Ramona De Amicis ◽  
Alessandro Leone ◽  
Simone Ravella ◽  
Giorgio Bedogni ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Fat Mass ◽  
Muscular Atrophy ◽  
Type I ◽  
Internal Validation ◽  
Spinal Muscular Atrophy Type ◽  
Children Development

SMN mRNA and protein levels in peripheral blood

Neurology ◽  
2006 ◽  
Vol 66 (7) ◽  
pp. 1067-1073 ◽  
Author(s):  
C. J. Sumner ◽  
S. J. Kolb ◽  
G. G. Harmison ◽  
N. O. Jeffries ◽  
K. Schadt ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Spinal Muscular Atrophy ◽  
Disease Severity ◽  
Peripheral Blood ◽  
Muscular Atrophy ◽  
Gene Copy ◽  
Blood Levels ◽  
Type I ◽  
Protein Levels ◽  
Smn Protein

Background: Clinical trials of drugs that increase SMN protein levels in vitro are currently under way in patients with spinal muscular atrophy.Objective: To develop and validate measures of SMN mRNA and protein in peripheral blood and to establish baseline SMN levels in a cohort of controls, carriers, and patients of known genotype, which could be used to follow response to treatment.Methods: SMN1 and SMN2 gene copy numbers were determined in blood samples collected from 86 subjects. Quantitative reverse transcription PCR was used to measure blood levels of SMN mRNA with and without exon 7. A cell immunoassay was used to measure blood levels of SMN protein.Results: Blood levels of SMN mRNA and protein were measured with high reliability. There was little variation in SMN levels in individual subjects over a 5-week period. Levels of exon 7-containing SMN mRNA and SMN protein correlated with SMN1 and SMN2 gene copy number. With the exception of type I SMA, there was no correlation between SMN levels and disease severity.Conclusion: SMN mRNA and protein levels can be reliably measured in the peripheral blood and used during clinical trials in spinal muscular atrophy, but these levels do not necessarily predict disease severity.

Sign in / Sign up

Export Citation Format

Share Document