Left ventricular clefts - incidental finding or pathologic sign of Wilson's disease?

Background: Wilson’s disease is an inherited autosomal recessive multi-systemic disorder characterized by reduced excretion and consequently excessive accumulation of copper in different organs, such as the heart. Results: In a prospective controlled trial, which is the largest to date, we evaluated 61 patients with Wilson’s disease, age- and sex-matched to 61 healthy patients, for cardiac manifestation using cardiac magnetic resonance imaging. Patients were under stable disease and had no signs of heart failure at the time of examination. We detected a left ventricular cleft, an invagination penetrating more than 50% wall thickness of the adjoining compact myocardium in diastole, in 20% of the patients (12 out of 61) compared to 5% among control patients (3 out of 61, p = 0.013). No correlation between the incidence of cleft and a certain genotype of Wilson’s disease was found. All described cases were incidental findings and none of the patients showed other signs of cardiac involvement. Conclusions: To conclude, the results of this study suggests that the increased occurrence of left ventricular clefts is due to Wilson’s disease. Large studies with a long observation period are needed for further evaluation

Alterations of lipid metabolism in Wilson disease

<p>Abstract</p> <p>Introduction</p> <p>Wilson disease (WD) is an inherited disorder of human copper metabolism, characterised by accumulation of copper predominantly in the liver and brain, leading to severe hepatic and neurological disease. Interesting findings in animal models of WD (Atp7b^-/-and LEC rats) showed altered lipid metabolism with a decrease in the amount of triglycerides and cholesterol in the serum. However, serum lipid profile has not been investigated in large human WD patient cohorts to date.</p> <p>Patients and Methods</p> <p>This cohort study involved 251 patients examined at the Heidelberg and Dresden (Germany) University Hospitals. Patients were analysed on routine follow-up examinations for serum lipid profile, including triglycerides, cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL). Data on these parameters at time of diagnosis were retrieved by chart review where available. For statistical testing, patients were subgrouped by sex, manifestation (hepatic, neurological, mixed and asymptomatic) and treatment (D-penicillamine, trientine, zinc or combination).</p> <p>Results</p> <p>A significant difference in total serum cholesterol was found in patients with hepatic symptoms, which diminished under therapy. No alterations were observed for HDL, LDL and triglycerides.</p> <p>Conclusion</p> <p>Contradictory to previous reports using WD animal models (Atp7b^-/-and LEC rats), the most obvious alteration in our cohort was a lower serum cholesterol level in hepatic-affected patients, which might be related to liver injury. Our data suggested unimpaired cholesterol metabolism in Wilson disease under therapy, independent of the applied medical treatment.</p

Vocal cord paralysis and rapid progressive motor neuron disease by the I113F mutation in SOD1 gene

Familial cases of amyotrophic lateral sclerosis are most frequently caused by mutation in the superoxide dismutase-1 (SOD1) gene. We report a heterozygous I113F mutation in a patient with familial ALS characterized by early and predominant bilateral vocal cord paralysis followed by descending spinal cord paresis. Modelling of the mutant SOD1 showed an alteration of the protein secondary structure leading to impaired strength of the dimer interface. This may result in a failure of the protein folding and subsequently generation of toxic intracellular aggregates, suggesting a pathogenic role for the mutation. © 2011 Informa Healthcare

Autonomic Dysfunction in Wilson's Disease: A Comprehensive Evaluation during a 3-Year Follow Up

Objectives: Wilson's disease is reported to have autonomic dysfunction, but comprehensive evaluation of autonomic function is lacking. Additionally, little is known about the change of autonomic function of Wilson's disease during continuous therapy. We assumed that patients with Wilson's disease had both sympathetic and parasympathetic autonomic impairments, and the autonomic dysfunction might be stable across a 3-year follow-up after years of optimal treatment.Methods: Twenty-six patients with Wilson's disease and twenty-six healthy controls were recruited. Twenty patients in the Wilson's disease group were examined again after a 3-year follow-up. All the participants were evaluated by a questionnaire on dysautonomia symptoms, 24-h blood pressure and heart rate monitoring, and cardiovascular autonomic function examination in various conditions including at rest, deep breathing, Valsalva maneuver, isometric handgrip test and passive tilting. Baroreflex sensitivity and spectral analyses were performed via trigonometric regressive spectral analysis.Results: Patients with Wilson's disease showed autonomic dysfunction mainly in the following aspects: (1) the heart rate was higher than the controls. (2) Valsalva ratio was lower in patients with Wilson's disease compared with the controls. (3) Heart rate increase during isometric hand gripping was smaller in the Wilson's disease patients than the controls. (4) Baroreflex sensitivity was lower during nearly all the cardiovascular autonomic function examinations compared with healthy controls. When tested 3 years later, baroreflex sensitivity at rest decreased compared with baseline. (5) There were mild declines of resting DBP and low frequency component of heart rate variability during the follow-up examination compared with baseline. (6) Subgroup analysis showed that patients initially presenting with neurological symptoms had a higher night-time heart rate, lower expiration: inspiration RR interval ratio (E/I ratio), lower expiration: inspiration RR interval difference (E-I difference), less increase of heart rate and diastolic blood pressure during the handgrip test, and lower baroreflex sensitivity during deep breathing than the control group. (7) Correlation analysis showed that the severity of neurological symptoms was associated with E/I ratio, E-I difference, Valsalva ratio, heart rate change during the handgrip test, and baroreflex sensitivity during deep breathing.Conclusions: The present study reveals cardiovascular autonomic dysfunction involving both sympathetic and parasympathetic branches in Wilson's disease patients, which is especially significant in the patients with neurological onset. Autonomic function is generally stable undergoing optimal maintenance treatment in patients with Wilson's disease. Though there might be mild changes of specific parameters

Evaluation of the Symptomatic Treatment of Residual Neurological Symptoms in Wilson Disease

The intention of this analysis was to identify patients with treated Wilson disease (WD) and residual neurological symptoms in order to determine whether or not they were undergoing any treatment in addition to the common decoppering medication. Moreover, the effects of any symptomatic medication were analyzed. Two samples of WD patients were investigated either by a mailed questionnaire survey (n = 135) or by a retrospective analysis (n = 75). A considerable proportion of patients still suffered from neurological symptoms (n = 106, 50.5%), of whom a relatively small proportion was treated symptomatically (n = 33, 31.1%). The documented effects varied substantially, with anticholinergics and botulinum toxin (against dystonia) and primidone (against tremor) apparently being the most promising compounds. Further studies are required to analyze the symptomatic treatment of WD patients with residual neurological symptoms in more detail.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich