Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy.

Sarcoglycanopathies include four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Delta-sarcoglycanopathy (LGMDR6) is the least frequent and is considered an ultra-rare disease. Our aim was to characterize the clinical and genetic spectrum of a large international cohort of LGMDR6 patients and to investigate whether or not genetic or protein expression data could predict a disease's severity. This is a retrospective study collecting demographic, genetic, clinical and histological data of patients with genetically confirmed LGMDR6 including protein expression data from muscle biopsies. We contacted 128 paediatric and adult neuromuscular units around the world that reviewed genetic data of patients with a clinical diagnosis of a neuromuscular disorder. We identified 30 patients with a confirmed diagnosis of LGMDR6 of which 23 patients were included in this study. Eighty-seven per cent of the patients had consanguineous parents. Ninety-one per cent of the patients were symptomatic at the time of the analysis. Proximal muscle weakness of the upper and lower limbs was the most common presenting symptom. Distal muscle weakness was observed early over the course of the disease in 56.5% of the patients. Cardiac involvement was reported in five patients (21.7%) and four patients (17.4%) required non-invasive ventilation. Sixty per cent of patients were wheelchair-bound since early teens (median age of 12.0 years). Patients with absent expression of the sarcoglycan complex on muscle biopsy had a significant earlier onset of symptoms and an earlier age of loss of ambulation compared to patients with residual protein expression. This study confirmed that delta-sarcoglycanopathy is an ultra-rare neuromuscular condition and described the clinical and molecular characteristics of the largest yet-reported collected cohort of patients. Our results showed that this is a very severe and quickly progressive disease characterized by generalized muscle weakness affecting predominantly proximal and distal muscles of the limbs. Similar to other forms of sarcoglycanopathies, the severity and rate of progressive weakness correlates inversely with the abundance of protein on muscle biopsy.

Genotype-Phenotype Correlation of the Childhood-Onset Bethlem Myopathy in the Mediterranean Region of Turkey.

OBJECTIVES: Collagen-VI-related myopathies are caused by both dominant and recessive mutations in the three collagen-VI-related genes (COL6A1, COL6A2, and COL6A3) and present as two different major clinical entities; Bethlem myopathy and Ullrich congenital muscular dystrophy. METHODS: In this study, we evaluated the clinical, pathologic, and genetic features of 8 patients with Bethlem myopathy from 3 families. RESULTS: We inspected disease course differences with age and mutations. Different variants in COL6A1 and COL6A2 genes were detected. Muscle MRI of the lower limbs showed a specific pattern of muscle involvement with variable severity of fatty infiltration. One family had essential hypertension. CONCLUSION: Genotype-phenotype correlation studies are critical in determining gene or mutation-targeted therapies, patient follow-up, severity and progression prediction, and genetic counselling.

No Local Findings after Subclavian Catheter Removal. Is Everything Alright? Case Report.

A 10-year-old male patient was admitted to the paediatric intensive care unit due to septic shock and oliguric acute renal failure. A haemodialysis catheter (11.5 Fr) was inserted into left subclavian vein for haemodialysis and cytokine-adsorption therapy. Haemodialysis and cytokine adsorption filter was applied to the patient for a total of two days, and then haemodialysis catheter was not used. The catheter was removed from the patient who was decided to transfer to the service on the fifth day of his admission. Tachycardia and hypotension developed and general condition deteriorated immediately after removal of the catheter. With rapid interventions, shock findings were corrected and the patient was reintubated and followed up in mechanical ventilation. On chest X-ray and thorax ultrasonography, the left hemithorax was completely filled, and a total of 1,500 mL of blood was drained by inserting a thorax tube. The patient was transferred to the paediatric pulmonology clinic after nine days of intensive care stay. Haemothorax development after subclavian catheter removal is a rare but a life-threatening condition. For these reasons, we believe that cases with removed subclavian or internal jugular vein catheters should be followed up for a suitable period of time.

Effects of Adrenocorticotropic Hormone Treatment on Heart Muscle in Patients with Infantile Spasm.

Background and aim Infantile spasm (IS) is a common epileptic syndrome of childhood epilepsies. The most effective treatment for IS is adrenocorticotropic hormone (ACTH). We hypothesized that ACTH treatment might change myocardial systolic and diastolic performance and cause cardiovascular side effects. This study aims to evaluate the effects of ACTH treatment on the heart muscle in IS patients. Materials and methods Eighteen newly diagnosed patients with IS participated in the study. ACTH (Synacthen® Depot) administered for two months in a total of 18 doses. A twelve-channel-surface electrocardiogram (ECG) and echocardiography performed in all patients before ACTH treatment, the second month after ACTH treatment (end of treatment), and two months later (after treatment). The systolic and diastolic myocardial functions were assessed by conventional and tissue Doppler imaging (TDI). Results The mean age of the patients was 8.1 months, and the patient group consisted of five female and 13 male subjects. None of the patients had clinically significant arrhythmia during treatment. After treatment, the mean heart rates of the patients significantly decreased (p=0.02), the systolic and diastolic blood pressures of patients did not change. We observed mild septal hypertrophy and an increase in the left ventricle mass index with ACTH treatment. Septal hypertrophy did not show progression until the fourth month after treatment. After ACTH treatment, patients had higher left ventricular myocardial performance index and lower E' and A' values at the mitral lateral annuli, however, these values didn't statistically significant from pretreatment values. Conclusion The low dose and short duration ACTH treatment in IS patients may cause subclinical myocardial hypertrophy. ACTH treatment has no significant side effects on cardiac functions.

A Rare Cause of Autism Spectrum Disorder: Megaconial Muscular Dystrophy.

Megaconial congenital muscular dystrophy (OMIM 602541) is defined by early-onset hypotonia, mildly elevated serum creatine kinase (CK) levels, muscle wasting, cardiomyopathy, psychomotor developmental delay and intellectual disability. The disease is caused by loss-of-function mutations in Choline kinase beta gene (CHKB) and has specific muscle biopsy findings. Here we investigate two patients with weakness of proximal muscles and generalized muscle atrophy, skin changes, agressiveness, social communication and empathy difficulties. Both patients had mildly elevated serum CK levels. Whole exome sequencing (WES) performed for both patients and homozygous c.818+1G>A and homozygous c.1031+1G>A variants were detected in patient 1 and patient 2, respectively. We would like to draw the attention of autism spectrum disorder in early diagnosis of congenital muscular dystrophies.

Hashimoto's encephalopathy in children: different manifestations of five cases.

Hashimoto's encephalopathy (HE) is a rare, poorly understood, progressive and relapsing, steroid-responsive multiform disease. HE presents with subacute cognitive dysfunction, psychiatric symptoms, seizures, and movement disorders. The disorder is usually related to thyroid disease and the most frequent feature is the presence of anti-thyroperoxidase antibodies. Patients are generally euthyroid or mildly hypothyroid. The clinical features of two patients at presentation included refractory seizures and confusion, another patient had behavioral problems and altered cognitive status, one patient presented with right-sided weakness and numbness especially in his leg and tongue, dysphagia, speech disorder, aggressiveness, nightmares and nocturnal enuresis and last patient had focal seizures with altered mental status. All patients manifested increased anti-thyroid antibodies. Four patients improved with steroid treatment, and one of the patients responded to plasmapheresis instead of corticosteroid treatment. Physicians' awareness of this complication is of great importance because HE is a highly treatable condition among children and adolescents.