Treatment of calcinosis with biphosphonates in juvenile dermatomyositis

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A case of chronic recurrent multifocal osteomyelýtýs successfully treated with etanercept

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MEFV mutations in systemic JIA

Background: Systemic form of juvenile idiopathic arthritis (JIA) is regarded as an autoinflammatory disease. Certain genetic polymorphisms in genes coding inflammatory proteins have been associated with the disease. On the other hand mutations of the MEFV gene cause a monogenic autoinflammatory disease, Familial Mediterranean Fever (FMF). In a previous study in adult rheumatoid arthritis 3 out of the 25 British patients who developed secondary amyloidosis had a mutation/polymorphism in the MEFV gene. Aim: To analyse whether mutaions in the MEFV gene had an association with systemic JIA. Patients and methods: MEFV mutations were screened in a total of 32 systemic JIA patients. All had been classified as systemic JIA according to the Durban JIA criteria. None had disease characteristics that met the Tel Hashomer criteria for the diagnosis of FMF. Results: 2 carrier for M694V and two patients who were homozygote for MEFV mutations. Both of these patients were among the most severe patients in the group. One had an excellent response to etanercept whereas the other was resistant to anti-TNF and other conventional treatments and had only a partial response to thalidomide. Although the number of severe mutations were increased in this small group of patients with systemic JIA the difference with the Turkish population did not reach statistical significance, but the disease causing mutation (M694V) was significantly high in the patients with systemic JIA(p = 0.02). Conclusion: However, the severe disease course in the aforementioned patients suggest that MEFV mutations may be a modifying genetic factor in systemic JIA.PubMe

Does unity of Familial Mediterranean fever with juvenile idiopathic arthritis affect the outcome?

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Unusual presentation of thyrotoxicosis as complete heart block and renal failure: a case report

<p>Abstract</p> <p>Introduction</p> <p>Thyrotoxicosis is a clinical entity often very difficult to diagnose without biochemical confirmation as its clinical features can be highly varied. The most common cardiac manifestations of thyrotoxicosis are resting sinus tachycardia, supraventricular tachycardia including atrial fibrillation and atrial flutter with or without cardiac failure. Bradycardia and atrio-ventricular conduction defects are very uncommon in thyrotoxicosis.</p> <p>Case presentation</p> <p>We report the case of a 59-year-old Caucasian man presenting with progressive weight loss, abnormal liver function, acute renal failure and complete heart block due to thyrotoxicosis.</p> <p>Conclusion</p> <p>Thyrotoxicosis should be considered as a possible diagnosis in patients with bradycardia and heart blocks associated with abnormal symptoms like weight loss. Nevertheless, the clinical, electrophysiological and biochemical abnormalities associated with thyrotoxicosis may be completely reversible restoring euthyroid state.</p

Genotype-phenotype correlation in seven motor neuron disease families with novel ALS2 mutations

Autosomal-recessive mutations in the Alsin Rho guanine nucleotide exchange factor (ALS2) gene may cause specific subtypes of childhood-onset progressive neurodegenerative motor neuron diseases (MND). These diseases can manifest with a clinical continuum from infantile ascending hereditary spastic paraplegia (IAHSP) to juvenile-onset forms with or without lower motor neuron involvement, the juvenile primary lateral sclerosis (JPLS) and the juvenile amyotrophic lateral sclerosis (JALS). We report 11 patients from seven unrelated Turkish and Yemeni families with clinical signs of IAHSP or JPLS. We performed haplotype analysis or next-generation panel sequencing followed by Sanger Sequencing to unravel the genetic disease cause. We described their clinical phenotype and analyzed the pathogenicity of the detected variants with bioinformatics tools. We further reviewed all previously reported cases with ALS2-related MND. We identified five novel homozygous pathogenic variants in ALS2 at various positions: c.275_276delAT (p.Tyr92CysfsTer11), c.1044C>G (p.Tyr348Ter), c.1718C>A (p.Ala573Glu), c.3161T>C (p.Leu1054Pro), and c.1471+1G>A (NM_020919.3, NP_065970.2). In our cohort, disease onset was in infancy or early childhood with rapid onset of motor neuron signs. Muscle weakness, spasticity, severe dysarthria, dysphagia, and facial weakness were common features in the first decade of life. Frameshift and nonsense mutations clustered in the N-terminal Alsin domains are most prevalent. We enriched the mutational spectrum of ALS2-related disorders with five novel pathogenic variants. Our study indicates a high detection rate of ALS2 mutations in patients with a clinically well-characterized early onset MND. Intrafamilial and even interfamilial diversity in patients with identical pathogenic variants suggest yet unknown modifiers for phenotypic expression

P450c17 Deficiency: Clinical and Molecular Characterization of Six Patients

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Distal renal tubular acidosis: ERKNet/ESPN clinical practice points

Distal renal tubular acidosis (dRTA) is characterised by an impaired ability of the distal tubule to excrete acid, leading to metabolic acidosis. Associated complications include bone disease, growth failure, urolithiasis and hypokalaemia. Due to its rarity, there is a limited evidence to guide diagnosis and management, however, available data strongly suggest that metabolic control of the acidosis by alkali supplementation can halt or revert almost all complications. Despite this, cohort studies show that adequate metabolic control is present in only about half of patients, highlighting problems with treatment provision or adherence. With these clinical practice points the authors, part of the working groups tubulopathies in the European Rare Kidney Disease Reference network (ERKnet) and inherited kidney diseases of the European Society for Paediatric Nephrology (ESPN) aim to provide guidance for the management of patients with dRTA to facilitate adequate treatment and establish an initial best practice standard against which treatment of patients can be audited

A novel form of recessive limb girdle muscular dystrophy with mental retardation and abnormal expression of alpha-dystroglycan

Cataloged from PDF version of article.The limb girdle muscular dystrophies are a heterogeneous group of conditions characterized by proximal muscle weakness and disease onset ranging from infancy to adulthood. We report here eight patients from seven unrelated families affected by a novel and relatively mild form of autosomal recessive limb girdle muscular dystrophy (LGMD2) with onset in the first decade of life and characterized by severe mental retardation but normal brain imaging. Immunocytochemical studies revealed a significant selective reduction of α-dystroglycan expression in the muscle biopsies. Linkage analysis excluded known loci for both limb girdle muscular dystrophy and congenital muscular dystrophies in the consanguineous families. We consider that this represents a novel form of muscular dystrophy with associated brain involvement. The biochemical studies suggest that it may belong to the growing number of muscular dystrophies with abnormal expression of α-dystroglycan. © 2003 Published by Elsevier B.V