Spinal Muscular Atrophy Research Articles

Computed tomography-based radiological gynecomastia in SBMA as an independent differential diagnostic biomarker: a retrospective study.

Spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS) are motor neuron disorders that demonstrate overlapping clinical features, especially in the early stage. Therefore, the aim of this study was to investigate the utility of chest tomography (CT) imaging in distinguishing between SBMA and ALS. This was a retrospective study reviewing CT images from patients with SBMA and sporadic ALS and those in the control group. The CT images were assessed to measure the diameter and morphology of glandular tissue associated with gynecomastia. We compared CT-measured gynecomastia between the SBMA, ALS, and control groups. Additionally, correlation analyses were performed between the quantitative measurements of gynecomastia obtained from CT scans and various clinical/laboratory parameter in the SBMA group. 15 chest CT images were collected from SBMA, 41 from ALS, and 29 from control group. No statistical differences were observed in BMI, functional scales, or age at the time of CT scans between the SBMA and ALS groups. Despite similar functional scales and age in both groups, the mean glandular tissue diameter of breast tissue observed in chest CT imaging differed significantly between SBMA, ALS, and controls: 32.22 ± 12.57mm, 15.91 ± 4.81mm, and 15.76 ± 7.26mm, respectively. This disparity allowed for the differentiation of SBMA from ALS and controls with statistical significance. Clinical gynecomastia was 80%, while radiological gynecomastia was 93.3% in SBMA. A significantly higher prevalence of diffuse glandular morphology pattern in SBMA (50%) was observed, contrasting with the predominance of nodular morphology in ALS and controls (9.1% and 20%). Correlative analysis between glandular tissue diameter and other clinical/laboratory parameters within the SBMA group showed no specific finding. CT-based radiological gynecomastia effectively differentiated SBMA from ALS. These findings support the usefulness of radiological gynecomastia as a potential differential diagnostic marker for SBMA, especially in the early stages.

Genetic Variability in Oxidative Stress, Inflammatory, and Neurodevelopmental Pathways: Impact on the Susceptibility and Course of Spinal Muscular Atrophy

The spinal muscular atrophy (SMA) phenotype strongly correlates with the SMN2 gene copy number. However, the severity and progression of the disease vary widely even among affected individuals with identical copy numbers. This study aimed to investigate the impact of genetic variability in oxidative stress, inflammatory, and neurodevelopmental pathways on SMA susceptibility and clinical progression. Genotyping for 31 genetic variants across 20 genes was conducted in 54 SMA patients and 163 healthy controls. Our results revealed associations between specific polymorphisms and SMA susceptibility, disease type, age at symptom onset, and motor and respiratory function. Notably, the TNF rs1800629 and BDNF rs6265 polymorphisms demonstrated a protective effect against SMA susceptibility, whereas the IL6 rs1800795 was associated with an increased risk. The polymorphisms CARD8 rs2043211 and BDNF rs6265 were associated with SMA type, while SOD2 rs4880, CAT rs1001179, and MIR146A rs2910164 were associated with age at onset of symptoms after adjustment for clinical parameters. In addition, GPX1 rs1050450 and HMOX1 rs2071747 were associated with motor function scores and lung function scores, while MIR146A rs2910164, NOTCH rs367398 SNPs, and GSTM1 deletion were associated with motor and upper limb function scores, and BDNF rs6265 was associated with lung function scores after adjustment. These findings emphasize the potential of genetic variability in oxidative stress, inflammatory processes, and neurodevelopmental pathways to elucidate the complex course of SMA. Further exploration of these pathways offers a promising avenue for developing personalized therapeutic strategies for SMA patients.

Respiratory Trajectories and Correlation with Serum Biochemical Indices in Spinal and Bulbar Muscular Atrophy

Background/Objectives: The primary life-threatening complication in spinal–bulbar muscular atrophy (SBMA) is ventilatory failure. The present study analyzes the longitudinal patterns of respiratory function tests over a follow-up of 11 years. Methods: We collected data from 9 genetically confirmed SBMA patients. Spirometric measurements [maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and forced vital capacity (FVC)], serum biochemical indices and SBMA functional rating scale (SBMAFRS) were collected every 6 months for 11 years. An average time curve was utilized to assess the changes in both pulmonary tests and serum biochemical indices of the patients. One-way repeated-measures ANOVA was applied to assess statistical differences. The Spearman’s rank correlation coefficient was utilized to evaluate the correlations between the respiratory function tests and serum biochemical and clinical indices. Results: A progressive decrease was observed in the respiratory function tests; the slope of the linear regression was significantly non-zero (p < 0.0001) for all three time curves. A major decrease was observed for MEP (52%) and MIP (42%), while this was minor for FVC (25%). SBMAFRS score correlated with FVC (r = 0.27), MIP (r = 0.53) and MEP (r = 0.51). MIP and MEP correlated with creatine phosphokinase (r = 0.3, r = 0.25, respectively) and MIP with creatinine levels (r = 0.31). Conclusions: This longitudinal study shows a progressive decline of spirometric data throughout life in SBMA patients. The decline appears to be related to clinical deterioration and muscle denervation. Spirometric measures relative to maximal strength of the respiratory muscles (MIP and MEP) may have a better predictive value for pulmonary and muscular decline than FVC.

SMN2 Copy Number Association with Spinal Muscular Atrophy Severity: Insights from Colombian Patients

SMN2 Copy Number Association with Spinal Muscular Atrophy Severity: Insights from Colombian Patients

MicroRNAs as Biomarkers in Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a severe neurodegenerative disease caused by the loss of the survival motor neuron (SMN) protein, leading to degeneration of anterior motor neurons and resulting in progressive muscle weakness and atrophy. Given that SMA has a single, well-defined genetic cause, gene-targeted therapies have been developed, aiming to increase SMN production in SMA patients. The SMN protein is likely involved in the synthesis of microRNAs (miRNAs), and dysregulated miRNA expression is increasingly associated with the pathophysiology of SMA. Currently, there is a lack of reliable biomarkers to monitor SMA; therefore, the search for novel SMA biomarkers, including miRNAs, is crucial as reliable tools are needed to track disease progression, predict the response to therapy and understand the different clinical outcomes of available treatments. In this review, we compile data on miRNAs associated with SMA pathogenesis and their potential use as biomarkers. Based on current knowledge, the most frequently deregulated miRNAs between SMA patients and controls, as well as pre- and post-treatment in SMA patients, include miR-1-3p, miR-133a-3p, miR-133b, and miR-206. These findings offer promising possibilities for improving patient classification and monitoring disease progression and response to treatment. Additionally, these findings provide insights into the broader molecular mechanisms and networks of SMA that could inform the development of future therapeutic strategies.

The impact of neurological impairment and tone on hip joint development

Purpose: The purpose of this study was to define how different force environments by neuromuscular diagnosis (hypertonic versus hypotonic) impact the growth and morphology of the proximal femoral and acetabular regions relative to typically developing children. Methods: Children with cerebral palsy and spinal muscular atrophy were compared with typically developing children aged 6 months to 11 years. Routine pelvic radiographs were evaluated using measures of hip geometry for the proximal femur and acetabulum. The data were analyzed using general linear models to estimate the developmental patterns according to age and diagnosis. Results: One hundred eighty-four children met the inclusion criteria: 58 spastic cerebral palsy Gross Motor Function Classification System I–V (263 hips), 32 spinal muscular atrophy (79 hips)), and 94 typically developing (187 hips) were included with a mean age of 4.9 ± 3.1 years. Using spinal muscular atrophy as a reference, significant differences in proximal femoral development included long thin versus short neck ( p < 0.01) and round versus flat epiphysis ( p = 0.001). A thin neck-wide epiphysis was found in spinal muscular atrophy versus thick neck-small epiphysis for typically developing ( p < 0.05). The ratio of acetabular width to proximal femoral epiphysis width differed significantly for typically developing ( p = 0.001) compared with cerebral palsy and spinal muscular atrophy. There was a negative correlation between migration percentage and acetabular width to epiphysis width in children with cerebral palsy, but no correlation in children with spinal muscular atrophy. Conclusion: Hip geometry was impacted by the force environment experienced during growth. These findings emphasize the crucial roles of gross motor function, muscle tone, and strength differences in determining hip morphology. Level of Evidence: III, retrospective case control.

The Impact of Nusinersen Treatment on Respiratory Function in Patients with Spinal Muscular Atrophy: A Systematic Review

Background/Objectives: This systematic review evaluated the impact of nusinersen therapy on respiratory health and function in individuals with spinal muscular atrophy (SMA) and determined whether nusinersen improves pulmonary function, focusing on differences based on patient age and the timing of treatment initiation. Methods: A systematic search of PubMed, Ovid Medline, ScienceDirect, and Web of Science databases was conducted up to January 2024 in accordance with the PRISMA guidelines. Thirteen studies were included, comprising clinical trials, observational studies, and case series that focused on respiratory outcomes in SMA patients treated with nusinersen. The data on study design, participant characteristics, nusinersen intervention, respiratory outcomes, and adverse events were extracted. The Joanna Briggs Institute Critical Appraisal Tool was used to assess study quality. A narrative synthesis was conducted to address the heterogeneity of the studies. Results: This review found a general trend of improvement in pulmonary function, specifically in forced vital capacity (FVC), although the extent and duration of improvement varied across the studies. Peak cough flow (PCF) and peak expiratory flow (PEF) showed positive trends in some studies, although the results were not consistently significant. Respiratory function improvements were frequently observed, particularly in younger patients and those treated earlier. Conclusions: Nusinersen appears to enhance respiratory function and improve motor outcomes in SMA patients, especially with early treatment. However, further research is needed to fully understand its mechanisms and long-term effects on respiratory health in SMA.

Effect of Nusinersen on Respiratory and Bulbar Function in Children with Spinal Muscular Atrophy: Correspondence.

Effect of Nusinersen on Respiratory and Bulbar Function in Children with Spinal Muscular Atrophy: Correspondence.

Treatment preferences in spinal muscular atrophy: A swing weighting study for caregivers of patients with SMA types 1 and 2.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterized by skeletal muscle weakness and atrophy. Patients with SMA types 1 and 2 develop severe disabilities conferring substantial patient and caregiver burden. Caregiver treatment characteristic preferences are useful for informing treatment choices and improving adherence. We aimed to identify drivers of SMA treatment preference from the perspective of caregivers of patients with SMA types 1 or 2 in the United States. We quantified the relative importance of different treatment characteristics and compared preferences for hypothetical treatment scenarios. Treatment attributes and attribute levels elicited were based on a literature search and interviews with caregivers and health care professionals. The most important treatment characteristics from the perspective of health care professionals and caregivers were identified and used in a survey to quantify relative importance for caregivers. Caregivers completed surveys regarding their preferences using swing weighting methodology. These results were used to estimate the relative value of four hypothetical SMA treatment scenarios exploring different modes of treatment administration. The swing weighting survey, completed by 20 caregivers, demonstrated that the attributes driving treatment preference were reduction in permanent ventilation needs and risk of severe adverse events, followed by treatment access (including cost coverage and availability), increased ability to sit without support, and less treatment administration burden. The hypothetical SMA treatment scenarios with the highest relative value offered an easier mode of administration, lowest risk of severe adverse events, less need of permanent ventilation, and highest ability of patients to feed and sit without support. Our findings suggest that caregivers prefer a treatment with reduced clinical burden and risk in which the cost is covered and treatment is available in the short term. These results can provide important contextual information for decision-makers and help promote patient-centered care for patients with SMA.

Combination of nusinersen and rehabilitation using hybrid assistive limb for type 3 spinal muscular atrophy

AbstractAn antisense oligonucleotide drug nusinersen can improve motor function of spinal muscular atrophy (SMA) patients. The Hybrid Assistive Limb (HAL) is a wearable robot assisting the wearers' movements in real time. Gait rehabilitation using HAL is useful for SMA. However, the efficacy of combined treatment has never been reported before. We have investigated the efficacy of combining both therapies. A 21‐year‐old man, genetically diagnosed with type 3 SMA, was treated by combining nusinersen and five sessions of gait rehabilitation using HAL over 2 years. Hammersmith Functional Motor Scale‐Expanded (HFMSE) score improved by 12 points after treatment. Electrophysiological parameters of the tibial nerves improved. Muscle volume also increased by 8% at 39 months. The combined therapy resulted in a good clinical outcome. This may be due to promotion of nerve regeneration and recovery of muscle volume by a synergy of nusinersen and motor learning correctly guided by HAL.

Update on Inherited Pediatric Motor Neuron Diseases: Clinical Features and Outcome.

Inherited pediatric motor neuron diseases (MNDs) are a group of neurodegenerative disorders characterized by the degeneration of motor neurons in the brain and the spinal cord. These diseases can manifest as early as infancy and originate from inherited pathogenic mutations in known genes. Key clinical features of MNDs include muscle weakness, hypotonia, and atrophy due to the degeneration of lower motor neurons or spasticity, hypertonia, and hyperreflexia caused by upper motor neuron dysfunction. The course of the disease varies among individuals and is influenced by the specific subtype. We performed a non-systematic, narrative clinical review, employing a systematic methodology for the literature search and article selection to delineate the features of hereditary pediatric motor neuron diseases. The growing availability of advanced molecular testing, such as whole-exome sequencing (WES) and whole-genome sequencing (WGS), has expanded the range of identified genetic factors. These advancements provide insights into the genetic complexity and underlying mechanisms of these disorders. As more MND-related genes are discovered, the accumulating genetic data will help prioritize promising candidate genes for future research. In some cases, targeted treatments based on specific genetic mechanisms have already emerged, underscoring the critical role of early and timely diagnosis in improving patient outcomes. Common MNDs include amyotrophic lateral sclerosis, spinal muscular atrophy, and bulbar spinal muscular atrophy. This narrative clinical review covers the clinical presentation, genetics, molecular features, and pathophysiology of inherited pediatric MNDs.

In Search of Spinal Muscular Atrophy Disease Modifiers

The 5q Spinal Muscular Atrophy (SMA) is a hereditary autosomal recessive disease caused by defects in the survival motor neuron (SMN1) gene encoding survival motor neuron (SMN) protein. Currently, it is the leading cause of infantile mortality worldwide. SMA is a progressive neurodegenerative disease with “continuum of clinical severity”, which can be modulated by genetic and epigenetic factors known as disease modifiers (DMs). Individuals (even siblings) with the same defects in SMN1 gene might have strikingly different types of SMA, supposedly due to the impact of DMs. There are several therapeutic options for SMA, all of them focusing on the restoration of the SMN protein levels to normal. Determining DMs and the pathways in which they are involved might aid in enhancing existing curative approaches. Furthermore, DMs might become novel therapeutic targets or prognostic biomarkers of the disease. This narrative review provides a brief overview of the genetics and pathobiology of SMA, and its bona fide modifiers. We describe novel, emerging DMs, approaches and tools used to identify them, as well as their potential mechanisms of action and impact on disease severity. We also propose several disease-modifying molecular mechanisms which could provide a partial explanation of the staggering variability of SMA phenotypes.

Acceptability, validity and responsiveness of inertial measurement units for assessing motor recovery after gene therapy in infants with early onset spinal muscular atrophy: a prospective cohort study

BackgroundOnasemnogene abeparvovec gene replacement therapy (GT) has changed the prognosis of patients with spinal muscular atrophy (SMA) with variable outcome regarding motor development in symptomatic patients. This pilot study evaluates acceptability, validity and clinical relevance of Inertial Measurement Units (IMU) to monitor spontaneous movement recovery in early onset SMA patients after GT.MethodsClinical assessments including CHOPINTEND score (the gold standard motor score for infants with SMA) and IMU measurements were performed before (M0) and repeatedly after GT. Inertial data was recorded during a 25-min spontaneous movement task, the child lying on the back, without (10 min) and with a playset (15 min) wearing IMUs. Two commonly used parameters, norm acceleration 95th centile (||A||_95) and counts per minute (||A||_CPM) were computed for each wrist, elbow and foot sensors.Results23 SMA-patients were included (mean age at diagnosis 8 months [min 2, max 20], 19 SMA type 1, three type 2 and one presymptomatic) and 104 IMU-measurements were performed, all well accepted by families and 84/104 with a good child participation (evaluated with Brazelton scale). ||A||_95 and ||A||_CPM showed high internal consistency (without versus with a playset) with interclass correlation coefficient for the wrist sensors of 0.88 and 0.85 respectively and for the foot sensors of 0.93 and 0.91 respectively. ||A||_95 and ||A||_CPM were strongly correlated with CHOPINTEND (r for wrist sensors 0.74 and 0.67 respectively and for foot sensors 0.61 and 0.68 respectively, p-values < 0.001). ||A||_95 for the foot, the wrist, the elbow sensors and ||A||_CPM for the foot, the wrist, the elbow sensors increased significantly between baseline and the 12 months follow-up visit (respective p-values: 0.004, < 0.001, < 0.001, 0.006, < 0.001, < 0.001).ConclusionIMUs were well accepted, consistent, concurrently valid, responsive and associated with unaided sitting acquisition especially for the elbow sensors. This study is the first reporting a large set of inertial sensor derived data after GT in SMA patients and paves the way for IMU-based follow-up of SMA patients after treatment.

Experiences and the psychosocial situation of parental caregivers of children with spinal muscular atrophy against the background of new treatment options: a qualitative interview study

BackgroundSpinal muscular atrophy is a rare neurodegenerative disorder in children which leads untreated to muscle wasting, respiratory impairments, and a shortened life expectancy. Parents as primary caregivers are often physically and psychologically burdened. In recent years, new and promising treatment options have been approved, but it remains unclear if they have an impact on the psychosocial situation of affected families.ObjectivesThe aim of this study was to explore the views and experiences of parents as informal caregivers of children with SMA in the course of the disease against the background of new treatment options (Spinraza® or Zolgensma®).MethodsWe conducted qualitative interviews with 27 parents of children with SMA treated with Spinraza® and Zolgensma® from April to September 2020. The analysis was done using thematic analysis and reported according to the COREQ criteria.ResultsThe data analysis resulted in three main themes: a) caregiver burden and negative consequences for families, b) resources and protective aspects, c) psychosocial care needs. The results are discussed against the background of new treatment options and previous models of supportive care needs. Parental caregivers of affected children face multiple burdens in different stages of the child’s disease progression.ConclusionAlthough new treatment options for SMA showed observable effects for most parents, the main caregiver burden and reported symptoms were attributable to the overburdening care tasks. To unburden families, more screening for unmet needs, family-centered help services, professional caregivers, childcare, and sufficient financial support are needed.

Intersession Intra-Rater and Inter-Rater Reliability of Myotonometer for Upper and Lower Extremity Muscles in Children with Spinal Muscular Atrophy.

Background/Objectives: This study aimed to examine intra- and inter-rater reliability of a myotonometer (MyotonPRO) in measuring upper and lower extremity mechanical properties in children with spinal muscular atrophy types I and II. Methods: Biceps brachii, triceps brachii, rectus femoris, and gastrocnemius muscle tone and stiffness in children (n = 21) were measured using the MyotonPRO device. Examiner 1 performed two sets of measurements in 60 min to determine intra-rater reliability. Examiner 2 performed measurements between Examiner 1's sets. Intra-interclass correlation coefficient, minimal detectable change, and standard error of measurement values were calculated to assess intra- and inter-rater reliabilities in this cross-sectional study. Results: The results showed excellent intra- and inter-rater reliability analyses for frequency and stiffness values except for the stiffness value of the gastrocnemius muscle, which presented good reliability (ICC = 0.71). Minimal detectable change values ranged from 0.59 to 1.98 Hz for muscle tone and 16.08 to 124.74 N/m for stiffness (for both intra- and inter-rater reliabilities). Conclusions: Our findings indicate that MyotonPRO is a reliable tool for quantifying upper and lower extremity mechanical properties within one session in children with spinal muscular atrophy types I and II. Mechanical properties of the extremity muscle can be determined using this easily applied tool in future studies.

Oral functions in adult persons with spinal muscular atrophy compared to a healthy control group: a prospective cross-sectional study with a multimodal approach

BackgroundOral function tests have been shown to reliably detect impaired bulbar function in adults with spinal muscular atrophy (SMA). Although not routinely recorded, it is known that persons with SMA are affected to varying degrees. Detecting differences in bite and tongue force, endurance, and maximum mouth opening has become particularly promising since the introduction of causal therapy for SMA. This study aimed to compare oral function among adult persons with SMA with different SMA types, walking abilities, and treatment status to a healthy control group.MethodsData from oral function tests conducted on 58 persons with SMA and 45 healthy individuals were analyzed. Differences in oral function between SMA subgroups were pairwise tested and compared to the healthy control group using Wilcoxon rank sum tests.ResultsIn an overall comparison, three out of five oral function tests revealed lower values for the SMA group compared to the control group. Subgroup analyses indicated lower scores for most oral function tests in non-ambulatory, untreated patients with SMA type 2 compared to controls. Ambulatory, treated patients with SMA type 3 achieved strength and endurance values comparable to those of healthy individuals.ConclusionsThe impairment of oral function varies across persons with SMA. Routine measurement of oral function is warranted to determine individual bulbar involvement stages. Further evaluation should be scheduled if indicators such as restricted maximum mouth opening arise.Trial registration DRKS, DRKS00015842. Registered 30 July 2019, https://drks.de/register/de/trial/DRKS00015842/preview.

Genotyping sequence-resolved copy-number variations using pangenomes reveals paralog-specific global diversity and expression divergence of duplicated genes.

Copy-number variable (CNV) genes are important in evolution and disease, yet sequence variation in CNV genes is a blindspot for large-scale studies. We present a method, ctyper, that leverages pangenomes to produce copy-number maps with allele-specific sequences containing locally phased variants of CNV genes from NGS reads. We extensively characterized accuracy and efficiency on a database of 3,351 CNV genes including HLA , SMN , and CYP2D6 as well as 212 non-CNV medically-relevant challenging genes. The genotypes capture 96.5% of underlying variants in new genomes, requiring 0.9 seconds per gene. Expression analysis of ctyper genotypes explains more variance than known eQTL variants. Comparing allele-specific expression quantified divergent expression on 7.94% of paralogs and tissue-specific biases on 4.7% of paralogs. We found reduced expression of SMN-1 converted from SMN-2, which potentially affects diagnosis of spinal muscular atrophy, and increased expression of a duplicative translocation of AMY2B . Overall, ctyper enables biobank-scale genotyping of CNV and challenging genes.

Acute Respiratory Failure in Children: A Clinical Update on Diagnosis.

Acute respiratory failure (ARF) is a sudden failure of the respiratory system to ensure adequate gas exchanges. Numerous clinical conditions may cause ARF, including pneumonia, obstructive lung diseases (e.g., asthma), restrictive diseases such as neuromuscular diseases (e.g., spinal muscular atrophy and muscular dystrophy), and albeit rarely, interstitial lung diseases. Children, especially infants, may be more vulnerable to ARF than adults due to anatomical and physiological features of the respiratory system. Assessing respiratory impairment in the pediatric population is particularly challenging as children frequently present difficulties in reporting symptoms and due to compliance and cooperation in diagnostic tests. The evaluation of clinical and anamnestic aspects represents the cornerstone of ARF diagnosis: first level exams (e.g., arterial blood gas analysis) confirm and evaluate the severity of the ARF and second level exams help to uncover the underlying cause. Prompt management is critical, with supplemental oxygen, mechanical ventilation, and the treatment of the underlying problem. The aim of this review is to provide a comprehensive summary of the current state of the art in diagnosing pediatric ARF, with a focus on pathophysiology, novel imaging applications, and new perspectives, such as biomarkers and artificial intelligence.

Low bone mineral density and its influencing factors in spinal muscular atrophy without disease-modifying treatment: a single-centre cross-sectional study

BackgroundChildren with spinal muscular atrophy (SMA) are at risk of low bone mineral density (BMD) and bone fragility. This study aims to assess lumbar spine BMD measured by quantitative computed tomography (QCT) and investigate influencing factors of low BMD in children with SMA without disease-modifying treatment.MethodsDemographic data, laboratory parameters, QCT data, and data on spinal radiographs were collected. A linear regression model was carried out to explore the correlations between BMD and its related factors.ResultsSixty-six patients with SMA who had complete records between July 2017 and July 2023 were analyzed, with SMA with a mean age of 5.4 years (range, 2.4–9.7 years), including type 1 in 14, type 2 in 37, and type 3 in 15. 28.8% of patients (19/66) were diagnosed with low BMD (Z-scores ≤ − 2), and the mean BMD Z-scores on QCT was − 1.5 ± 1.0. In our model, BMD Z-scores was associated with age (β=-0.153, p = 0.001). SMA phenotype and serum bone metabolism markers, such as serum phosphorus (P), alkaline phosphatase (ALP) and 25-Hydroxyvitamin D (25-OH-D) levels did not independently predict low BMD. ROC analysis showed that the age ≥ 6.3 years predicts a Z-scores ≤ -2.0 with a sensitivity of 68.4% and a specificity of 68.1%.ConclusionsLow BMD were highly prevalent in children with SMA without disease-modifying treatment in our centre. Regular monitoring of BMD is necessary for all types of SMA children, especially those aged ≥ 6.3 years.

Spinal muscular atrophy carrier screening program: awareness and attitude of healthcare professionals in Turkey.

Spinal Muscular Atrophy (SMA) is an autosomal recessive disease caused by variants in the SMN1 gene, leading to progressive muscle weakness. The carrier frequency of SMN1 gene variants, including variant and copy number variations, is estimated to be around 1 in 50 people, while the global prevalence of SMA is 1-3 per 10,000 live births. In response to the increasing carrier proportion, especially due to consanguineous marriages, Turkey launched the SMA Carrier Screening Program in 2021. Notably, recent SMA cases have been observed in the children of healthcare workers who did not undergo carrier screening, prompting us to evaluate their awareness of this program. After receiving ethics approval, 1,322 healthcare professionals completed a 15-item survey based on the SMA Carrier Screening Guidelines. Of these, 5.8% were unaware of SMA, and 26% lacked information about the national screening program. Awareness of the screening program was significantly lower among secondary and tertiary healthcare professionals compared to primary healthcare professionals (p < 0.0001) and among non-physician healthcare professionals compared to physicians (p < 0.0001). Additionally, a serious lack of knowledge was observed concerning the parts of the screening covering the pregnancy period. Although there is generally high awareness of the SMA Carrier Screening Program among healthcare professionals, significant knowledge gaps exist. These findings highlight the need for increased efforts to more effectively deliver screening programs and continue the education of healthcare professionals. Education and awareness campaigns can enhance program awareness and effectiveness, reach wider audiences, and contribute to preventive measures for the health of future generations.