Experiences in the molecular genetic and histopathological evaluation of calpainopathies.

Calpainopathy is mainly characterized by symmetric and progressive weakness of proximal muscles. Several reports showed that the most common LGMD subtype is LGMDR1 or calpainopathy, which had previously been defined as LGMD2A. Until now, more than 500 likely pathogenic/pathogenic variants in the CAPN3 gene have been reported. However, a clear genotype-phenotype association had not yet been established and this causes major difficulties in predicting the prognosis in asymptomatic patients and in providing genetic counseling for prenatal diagnosis. In this report, we aimed to add new data to the literature by evaluating 37 patients with likely pathogenic/pathogenic variants for the detected variants' nature, patients' phenotypes, and histopathological features. As a result, the general clinical presentation of the 23 different variants was presented, the high frequency of NM_000070.3:c.550delA mutation in Exon 4 was discussed, and some novel genotype-phenotype associations were suggested. We have underlined that calpainopathy can be misdiagnosed with inflammatory myopathies histopathologically. We have also emphasized that, in young or adult patients with mild to moderate proximal muscle weakness and elevated CK levels, calpainopathy should be the first suspected diagnosis.

Bone mineral density and vitamin D levels in patients with group a COPD.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is a chronic, inflammatory airway disease associated with osteoporosis. Reduced bone mineral density (BMD) and impaired bone quality were shown to cause increased bone fragility and fractures in COPD patients. The aim of this study was to evaluate vitamin D levels and BMDs in Group A COPD patients. METHODS: This case-control study involved 33 males aged 50 or above diagnosed with Group A COPD and 44 age-matched healthy males. Participants' serum vitamin D and other indicators were evaluated as well as lumbar and hip BMD of COPD patients. RESULTS: Vitamin D levels were significantly lower in COPD patients (15.13 ± 6.02 ng/L) than controls (21.89 ± 4.49 ng/L). Two patients had a history of thoracic vertebral fracture. Lumbar (L1-L4) T scores were normal in 16 patients (48.5%) and indicated osteopenia in 15 (45.5%) and osteoporosis in 2 (6%). Hip femur total T scores were normal in 19 patients (57.6%) and indicated osteopenia in 14 (42.4%). CONCLUSION: Vitamin D deficiency/insufficiency is prevalent in COPD patients, and BMD decreases in the early period of the disease. Vitamin D and BMD should be evaluated in the early stages to prevent osteoporosis and its complications in COPD patients.

Impact of next-generation sequencing panels in the evaluation of limb-girdle muscular dystrophies.

INTRODUCTION: Limb-girdle muscular dystrophy (LGMD) is the fourth most common muscular dystrophy, with progressive proximal muscle weakness. However, a large number of neuromuscular conditions are similarly presented. Because of this, the use of high-throughput methods such as next-generation sequencing (NGS) is important in the evaluation of LGMD. METHODS: In this report, we applied a custom target capture-based NGS panel covering 31 LGMD-associated genes (MYOT, LMNA, CAV3, DES, DNAJB6, FLNC, CAPN3, DYSF, SGCG, SGCA, SGCB, SGCD, TCAP, TRIM32, FRKP, TTN, POMT1, ANO5, FKTN, POMT2, POMGnT1, DAG1, PLEC, GAA, GMPPB, HNRNPDL, TNPO3, LIMS2, POMK, TRAPPC11, ISPD) in 74 patients suspected of LGMD. RESULTS: In 25 (33.8%) out of 74 patients analyzed, one or more pathogenic/likely pathogenic variants in 13 different genes were detected. Six of the patients had the variants that were not found in databases and literature; thus, they were interpreted as novel pathogenic variants. DISCUSSION: The diagnosis rate achieved (33.8%) is consistent with previous literature reports and underlines the efficiency and importance of NGS technology in the molecular genetic evaluation of LGMD.

Correlations among enthesitis, clinical, radiographic and quality of life parameters in patients with ankylosing spondylitis.

OBJECTIVES: To investigate the relationship between enthesitis and disease activity, functional status, fatigue, joint mobility, radiological damage, laboratory parameter and quality of life in patients with ankylosing spondylitis (AS). METHODS: A total of 421 patients with AS (323 male and 98 female) who were included in the Turkish League Against Rheumatism Registry were enrolled in the study. The Bath AS Disease Activity Index (BASDAI), fatigue, the Bath AS Functional Index (BASFI), the Bath AS Metrology Index (BASMI), the Maastricht AS Enthesitis Score (MASES), AS quality of life (ASQoL), the Bath AS Radiology Index (BASRI) and erythrocyte sedimentation rate (ESR) were evaluated. RESULTS: Enthesitis was detected in 27.3% of patients. There were positive correlations between MASES and BASDAI, BASFI and fatigue (p < 0.05). MASES was not correlated with BASRI, BASMI, ASQoL and ESR. The mean MASES score was 1.1 ± 2.4. The most frequent regions of enthesopathies were right iliac crest, spinous process of L5 and proximal to the insertion of left achilles tendon, respectively. CONCLUSIONS: Enthesitis was found to be associated with higher disease activity, higher fatigue, worse functional status and lower disease duration. As enthesitis was correlated with BASDAI, we conclude that enthesitis can reflect the disease activity in patients with AS.

The relationship of ischemia-modified albumin levels to disease activity scores and HLA-B27 in patients with ankylosing spondylitis.

OBJECTIVE: Recent studies have implicated increased oxidative stress in the pathogenesis of Ankylosing spondylitis (AS). Ischemia-modified albumin (IMA), an altered form of albumin, increases oxidative stress. This study aimed to investigate the relationship between IMA levels and other indicators of disease severity in AS. METHODS: This study included 63 AS patients and 48 healthy controls. Patients were examined for serum lipid profile, C-reactive protein (CRP), complete blood count, Bath Ankylosing Spondylitis Disease Activity Index, human leukocyte antigen (HLA) B27, and treatment regimen. They were categorized based on disease activity, HLA-B27 status, and the drug treatment and compared for IMA levels. RESULTS: The patients had significantly higher IMA levels than controls (p=0.020); among patients, the levels were higher in those with active disease (p=0.001) and positively correlated with the CRP levels. No significant difference was found between the IMA levels of the patients with different HLA-B27 status or treatment method. CONCLUSION: The IMA levels were higher in patients than controls and further increased in patients with active AS. IMA was associated with disease activity and can be used as an inflammatory marker in AS. More comprehensive future studies with a larger sample size may help understand the relationship in greater detail.

The relationship between scoliosis and upper extremity functions in patients with Duchenne muscular dystrophy.

OBJECTIVES: The aim of this study was to investigate the relationship between scoliosis and upper extremity functions in patients with Duchenne muscular dystrophy (DMD). PATIENTS AND METHODS: Between January 2018 and July 2018, a total of 55 patients (54 males, 1 female; mean age: 9.9±2.9 years; range, 6 to 15 years) who were diagnosed with DMD based on the clinical, laboratory, muscle biopsy and molecular analysis results were included in this cross-sectional study. Scoliosis was evaluated and Cobb angles were measured. Functional Ambulation Scale and Brooke and Vignos scale scores were recorded. The ABILHAND-Kids questionnaire and Nine-Hole Peg Test (9-HPT) were used to assess the upper extremity functions. Hand grip strengths were also evaluated. RESULTS: The median ABILHAND-Kids scores and the hand grip strength values of the patients without scoliosis were significantly higher compared to those with scoliosis (p=0.002 and p=0.004 for right hand and p=0.012 for left hand, respectively). There was no statistically significant difference in the 9-HPT scores between the patients with and without scoliosis (p>0.05). We found a negative, significant correlation between the Cobb angle and ABILHAND-Kids scores in patients with scoliosis (r=-0.503; p=0.017). CONCLUSION: Our study results show a moderate relationship between scoliosis and upper extremity functions. Scoliosis may adversely affect upper extremity functions in patients with DMD.

The relationship of bone mineral density and vitamin D levels with steroid use and ambulation in patients with Duchenne muscular dystrophy.

OBJECTIVES: This study aims to assess the bone mineral density (BMD) and serum levels of 25(OH)-vitamin D and their relationship with steroid use and ambulation in patients with Duchenne muscular dystrophy (DMD). PATIENTS AND METHODS: Between January 2017 and May 2018, medical records of a total of 67 male patients (mean age, 13.9±4.3 years; range, 8 to 25 years) who were diagnosed with definite DMD were retrospectively analyzed. Demographic data, functional activity level, steroid use, fracture history and location, serum levels vitamin D, and lumbar and hip Z-scores in BMD at the time of the initial admission were recorded. RESULTS: The mean level of vitamin D was 13.4±7.5 ng/mL. In terms of serum levels of vitamin D, 28 patients (41.8%) had severe deficiency, 31 (46.3%) had insufficiency, and five patients (7.5%) had deficiency. Only three (4.5%) of the patients had sufficient levels of vitamin D. The hip Z-scores were significantly lower than lumbar Z scores. There was no significant difference in the lumbar and hip BMD measurements between the patients with and without steroid use. Lumbar Z-scores were significantly lower in non-ambulatory patients than ambulatory patients. CONCLUSION: It is of utmost importance to evaluate the initial serum vitamin D levels in terms of bone health and prescribe replacement in case of deficiency/insufficiency in DMD patients. Since the decrease in the BMD is evident in this patient population, maintaining the mobilization as long as possible, providing loading on the bone for a long time, may be beneficial.

Effects of motor-motor and motor-cognitive tasks on balance in patients with multiple sclerosis.

BACKGROUND: Dual tasking is frequently impaired in Multiple Sclerosis (MS), substantially impairing quality of life (QoL). We aimed to examine the effects of motor-motor and motor-cognitive tasks on balance in highly mobile patients with relapsing-remitting MS (RRMS), with mild disability. METHODS: Thirty-eight patients and 34 controls were included. Steady Stance Test (SST), Berg Balance Scale (BBS) and Activities-specific Balance Confidence Scale (ABC) were used to evaluate the balance. Expanded Disability Status Scale (EDSS), Mini-mental State Examination (MMSE), Beck Depression Inventory (BDI) and Fatigue Impact Scale (FIS) were used to evaluate disability, cognitive impairment, depression and fatigue, respectively. RESULTS: BBS and ABC scores were significantly different between the groups. Also, balance was significantly impaired in patients. Eyes-open left single stance test was the most efficient test to reveal the balance impairment in RRMS patients independent of dual-task. Physical component of FIS affected this test independent of age and BMI. Visual input significantly increased the stance durations in majority of SST, especially in tough stance positions with reduced balance area. However, visual input during dual-tasking impaired the balance. In addition, eyes-closed left tandem stance test with MM dual task significantly improved the balance in patients. BBS was significantly correlated with EDSS(r: -0.336), ABC(r: 0.688), FIS physical subgroup(r: -0.614) and FIS social subgroup(r: -0.475). CONCLUSION: Dual-tasking improves balance and increases QoL in patients with RRMS. Eyes closed balance treatment with motor-dual task could be beneficial.

Comparison of isokinetic exercise versus standard exercise training in patients with chronic low back pain: a randomized controlled study.

OBJECTIVE: To compare the effectiveness of an isokinetic exercise programme and a standard exercise programme in patients with chronic low back pain in terms of pain, mobility, disability, psychological status and muscle strength. DESIGN: A randomized controlled trial. SETTING: An outpatient rehabilitation clinic. SUBJECTS: A total of 40 patients with low back pain were included in the study. INTERVENTIONS: Patients with low back pain were randomly allocated into group 1 (n=20, isokinetic exercises) and group 2 (n=20, standard exercise). MAIN MEASURES: Outcome measures included a visual analogue scale (VAS) for pain, fingertip-to-floor test for spinal mobility, Modified Oswestry Low Back Disability Questionnaire (MOLBDQ), Beck Depression Inventory and isokinetic muscle testing. RESULTS: The isokinetic and standard exercise groups demonstrated significant improvement in the VAS, fingertip-to-floor test, MOLBDQ, Beck Depression Inventory scores, and muscle strength compared with the baseline that persisted until the end of the first month (P<0.05). Comparison of both exercise groups in terms of these parameters obtained at the end of the treatment and at the first month after treatment showed no significant difference (P>0.05). CONCLUSION: Isokinetic and standard exercise programmes have an equal effect in the treatment of low back pain, with no statistically significant difference found between the two programmes. The standard exercise programme was easily performed and had a low cost, making it the preferred option for exercise.