Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Barth syndrome (BTHS) is an X-linked disorder characterised by cardiomyopathy, neutropenia, skeletal myopathy and growth delay. This study describes the UK national clinical experience and outcome of cardiomyopathy in BTHS. The clinical course and echocardiographic changes of all patients with BTHS in the UK were reviewed from 2004 to 2014. In addition, strain analysis using 2D speckle tracking echocardiography was performed to further assess left ventricular function in the most recent follow-up. At last follow-up, 22 of 27 patients were alive with a median age of 12.6 (2.0-23.8) years; seven underwent cardiac transplantation at a median age of 2 (0.33-3.6) years, and five died (18.5%) at a median age of 1.8 (0.02-4.22) years. All deaths were related to cardiomyopathy or its management. Left ventricular diastolic dimension and systolic function measured by fractional shortening tended to normalise and stabilise after the first 3 years of life in the majority of patients. However, patients with BTHS (n = 16) had statistically significant reduction in global longitudinal and circumferential strain compared to controls (n = 18), (p < 0.001), despite apparent normal conventional measures of function. There was also reduced or reversed apical rotation and reduced left ventricular twist. Sustained ventricular arrhythmia was not seen at follow-up. Cardiac phenotype in BTHS is variable; however, longer-term outcome in our cohort suggests good prognosis after the first 5 years of life. Most patients appeared to have recovered near normal cardiac function by conventional echocardiographic measures, but strain analysis showed abnormal myocardial deformation and rotational mechanics.
Pediatr Cardiol 2016 Jan
PMID:Clinical Characteristics and Outcomes of Cardiomyopathy in Barth Syndrome: The UK Experience. 2633 10

Mutations in the gene tafazzin (TAZ) result in Barth syndrome (BTHS). Patients present with hypotonia, cyclic neutropenia, 3-methyglutaconic aciduria, and cardiomyopathy, which is the major cause of mortality. The recessive, X-linked TAZ gene encodes a mitochondrial membrane-associated phospholipid modifying enzyme, which adds unsaturated fatty acid species to monolysocardiolipin to generate mature cardiolipin in the mitochondrial membrane that is essential for mitochondrial morphology and function. To identify intrinsic mitochondrial localization sequences in the human TAZ protein, we made sequential TAZ peptide-eGFP fusion protein expression constructs and analyzed the localization of eGFP fluorescence by confocal microscopy. We assessed these fusion proteins for mitochondrial localization through cotransfection of H9c2 cells with plasmids encoding organellar markers linked to TdTomato. We have identified two peptides of TAZ that are independently responsible for mitochondrial localization. Using CRISPR-generated TAZ knock out cell lines, we found that these peptides are able to direct proteins to mitochondria in the absence of endogenous TAZ. These peptides are not located within the predicted enzymatic clefts of TAZ, implying that some BTHS disease causing mutations may affect mitochondrial localization without affecting transacylase activity. These novel peptides improve our understanding of TAZ intracellular trafficking, provide insight into the molecular basis of BTHS and provide molecular reagents for developing targeted mitochondrial therapies.
J Mol Cell Cardiol 2018 01
PMID:Identification of novel mitochondrial localization signals in human Tafazzin, the cause of the inherited cardiomyopathic disorder Barth syndrome. 2912 3

Giant cell arteritis is a granulomatous immune-mediated vasculitis of medium and large vessels. It most commonly affects white females over the age of 50 and is the most common primary vasculitis in the United States. Treatment of this disease has classically been with high-dose corticosteroids, but this therapy has been associated with severe morbidity and mortality. Tocilizumab, a humanized monoclonal antibody targeting the interleukin-6 receptor, has been used with great efficacy and safety in rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis. As interleukin-6 has been shown to be a key cytokine in giant cell arteritis, the use of an inhibiting agent has been explored. In the 15 case reports/series that were reviewed, most patients were given tocilizumab due to refractory giant cell arteritis and/or intolerance to glucocorticoid therapy, and most experienced remission of symptoms. At this time, there are only 2 randomized control trials to evaluate the efficacy and safety of tocilizumab use in giant cell arteritis. The phase II trial by Villiger et al and the GiACTA trial both showed that tocilizumab greatly increased the rate of sustained remission in giant cell arteritis over the course of 1 year. The most common adverse events were similar to those seen with use in rheumatoid arthritis: infections, neutropenia, and increases in lipids and liver function test enzymes. Based on the results of numerous case studies and the 2 randomized control trials, tocilizumab is the first agent to be approved by the Food and Drug Administration for treatment of giant cell arteritis.
Cardiol Rev
PMID:Tocilizumab in Giant Cell Arteritis. 2957 Apr 75


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