Identification of a Novel ARSA Gene Mutation Through High-Throughput Molecular Diagnosis Method in Two Girls with Late Infantile Metachromatic Leukodystrophy.

Metachromatic leukodystrophy (MLD) is a rare leukoencephalopathy caused by pathogenic mutations in the ARSA gene. It manifests as severe motor symptoms, mental problems, and sometimes, seizures. We aimed to investigate the phenotypic manifestations and genetic causes of MLD in an Iranian family. We present the case of a 3-year-old girl who presented with hypotonia, muscular atrophy, and seizures. Neurological and neuromuscular examinations were performed to evaluate clinical characteristics. Whole exome sequencing (WES) was used to detect disease-causing variants. In silico analysis was performed to predict the pathogenicity of this variant. GROMACS software was utilized for molecular dynamic simulation (MDS). Neurological studies revealed marked slowing of motor conduction velocities and an increased motor unit action potential duration. Brain MRI scan revealed white matter abnormalities. By applying WES, we identified a novel homozygous missense variant (NM_000487.6, c.938G > C, p.R313P) in ARSA. Direct sequencing identified this homozygous variant in her asymptomatic younger sister, whereas both parents carried a heterozygous variant. This mutation has not been reported in genetic databases or in literature. In silico analysis predicted that any variation in this DNA position would cause disease, as it is highly conserved. The c.938G > C variant was classified as a pathogenic variant according to ACMG/AMP guidelines. MDS analysis indicated that c.938G > C had a significant impact on both the structure and stabilization of ARSA, ultimately resulting in impaired protein function. The identification of this variant expands the spectrum of ARSA gene mutations associated with MLD and highlights the importance of genetic testing for the diagnosis of MLD.

Comparison of Dextrose Prolotherapy and Triamcinolone Intraarticular Injection on Pain and Function in Patients with Knee Osteoarthritis - A Randomized Clinical Trial.

Background: The present study was performed to assess the therapeutic effects of combined intra and extraarticular dextrose prolotherapy on knee osteoarthritis and its comparison with intra- articular triamcinolone injection. Methods: In this study, 50 patients suffering from knee osteoarthritis were allocated into two groups as a double-blind randomized clinical trial. The first group received one session of dextrose prolotherapy as one intra-articular injection of 10cc dextrose 16% and periarticular intradermal injections of dextrose 12% at 4 points around the knee (2.5 cc at each point). The second group underwent therapy with one intra-articular injection of triamcinolone (40 mg). Results: Compared to pretreatment, both interventions caused significant improvement in pain (evaluated by VAS) and WOMAC (all its components) in 1 and 3 months postintervention (all with P-value < 0.005). In the first month, pain reduction was significantly better in corticosteroid group (P-Value 0.002 and 0.048 respectively). In third month post intervention, improvements in VAS and WOMAC components were significantly greater in prolotherapy group. Conclusions: Both methods of corticosteroid and dextrose prolotherapy (combined intra and extraarticular technique) are effective on pain and function of patients with knee osteoarthritis. Compared to corticosteroid, prolotherapy method was associated with less pain reduction in short- term, but its effects were more persistent and in midterm examinations (3 months), it was more effective than corticosteroid.

Efficacy of High-Power Laser in Alleviating Pain and Improving Function of Patients With Patellofemoral Pain Syndrome: A Single-Blind Randomized Controlled Trial.

Introduction: In this study, a single-blind and randomized controlled trial (RCT) for assessing the effectiveness of high-power (up to 12 W) laser therapy (HPLT) on patients with patellofemoral pain syndrome (PFPS) was carried out. Methods: Forty-four patients were randomly assigned to two treatment groups by generating random numbers with MATLAB 2014b software, where odd and even numbers were attributed to sham laser group (group A) and actual laser group (group B), respectively. Group B patients underwent HPLT with total dose of 300 J/session for 5 consecutive sessions separated by a 2-day interval. On the other hand, sham laser was applied to group A patients. Both groups had the same exercise therapy programs during the study period (3 months). The exercise therapy program included isometric knee exercise for 3 sets per day and 10 times in each set, with duration of 10 seconds per time and straight leg raise for 15 seconds 10 times a day. The group codes of patients were not revealed to subjects and data analyzer until completion of the study. Kujala, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analog scale (VAS) questionnaires were chosen as outcome measures. These questionnaires were completed at three points during the study; at the beginning of the study to obtain the pre-therapy conditions and one month and three months after the start of the study to evaluate post-therapy conditions. Results: Two main analyses were conducted: within-group and between-group analyses. Withingroup analyses indicated significant improvements in respect to all measurements where pretherapy and post-therapy comparisons were conducted in both groups (P < 0.05). On the other hand, between-group comparisons did not reveal any statistically significant functional difference between group A and group B regarding the evaluative criteria (P > 0.05) except for pain VAS (P < 0.05). Conclusion: This study indicated that short-term HPLT accompanied by appropriate exercise regimen significantly decreased pain in patients with PFPS. But it was not recommended as an efficient modality in functional improvement. Also, it was observed that, in the short-term period of study, HPLT was a safe modality.