Acta paediatrica (Oslo, Norway : 1992). Supplement最新文献

{"title":"Stones, bones, and heredity.","authors":"Dawn S Milliner","doi":"10.1080/08035320600649440","DOIUrl":"https://doi.org/10.1080/08035320600649440","url":null,"abstract":"<p><p>Genetic disorders of mineral metabolism cause urolithiasis, renal disease, and osteodystrophy. Most are rare, such that the full spectrum of clinical expression is difficult to appreciate. Diagnosis is further complicated by overlap of clinical features. Dent's disease and primary hyperoxaluria, inherited causes of calcium urolithiasis, are both associated with nephrocalcinosis and urolithiasis in early childhood and renal failure that can occur at any age but is seen more often in adulthood. Bone disease is an inconsistent feature of each. Dent's disease is caused by mutations of the CLCN-5 gene with impaired kidney-specific CLC-5 chloride channel expression in the proximal tubule, thick ascending limb of Henle, and the collecting ducts. Resulting hypercalciuria and proximal tubule dysfunction, including phosphate wasting, are primarily responsible for the clinical manifestations. Low-molecular-weight proteinuria is characteristic. Definitive diagnosis is made by DNA mutation analysis. Primary hyperoxaluria, type I, is due to mutations of the AGXT gene leading to deficient hepatic alanine-glyoxylate aminotransferase activity. Marked overproduction of oxalate by hepatic cells results in the hyperoxaluria responsible for clinical features. Definitive diagnosis is by liver biopsy with measurement of enzyme activity, with DNA mutation analysis used increasingly as mutations and their frequency are defined. These disorders of calcium urolithiasis illustrate the value of molecular medicine for diagnosis and the promise it provides for innovative and more effective future treatments.</p>","PeriodicalId":76973,"journal":{"name":"Acta paediatrica (Oslo, Norway : 1992). Supplement","volume":"95 452","pages":"27-30"},"PeriodicalIF":0.0,"publicationDate":"2006-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/08035320600649440","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26111928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mainz Severity Score Index (MSSI): development and validation of a system for scoring the signs and symptoms of Fabry disease.","authors":"Michael Beck","doi":"10.1080/08035320600618825","DOIUrl":"https://doi.org/10.1080/08035320600618825","url":null,"abstract":"<p><strong>Unlabelled: </strong>Fabry disease is a rare lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme alpha-galactosidase A. The resultant storage of undegraded glycolipids leads to the progressive development of potentially life-threatening manifestations affecting multiple organ systems in the body. This paper describes the development of the Mainz Severity Score Index (MSSI), a scoring system for patients with Fabry disease.</p><p><strong>Conclusion: </strong>The MSSI score has been proven to be representative in patients with 'classic' Fabry disease and may be useful for monitoring clinical improvement in patients receiving enzyme replacement therapy.</p>","PeriodicalId":76973,"journal":{"name":"Acta paediatrica (Oslo, Norway : 1992). Supplement","volume":"95 451","pages":"43-6"},"PeriodicalIF":0.0,"publicationDate":"2006-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/08035320600618825","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26039883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversibility of cellular and organ pathology in enzyme replacement trials in animal models of lysosomal storage diseases.","authors":"Volkmar Gieselmann","doi":"10.1111/j.1651-2227.2006.tb02397.x","DOIUrl":"10.1111/j.1651-2227.2006.tb02397.x","url":null,"abstract":"<p><strong>Unlabelled: </strong>Enzyme replacement therapy (ERT) has now become a feasible treatment option for several lysosomal storage diseases (LSDs). Although the rationale behind this approach is straightforward, there are many factors that may influence the efficacy of treatment. The reversibility of cellular and organ pathology depends on several factors including the particular organ targeted, the dose and biodistribution of enzyme, the accessibility of the target cell to the infused enzyme, the abundance of receptors for mannose-6-phosphate and other ligands in the target tissue and the activity of endocytosis. In addition, each lysosomal enzyme is unique and its ability to reverse pathology must be individually determined according to source, glycosylation and phosphorylation status. The extent to which cellular pathology may be corrected depends upon the delivery of sufficient enzyme to the diseased tissues.</p><p><strong>Conclusion: </strong>Studies in animal models have identified numerous factors that influence the therapeutic efficacy of ERT. This would suggest that in patients affected by LSDs rigorous evaluation of each therapeutic preparation will be needed.</p>","PeriodicalId":76973,"journal":{"name":"Acta paediatrica (Oslo, Norway : 1992). Supplement","volume":"95 451","pages":"93-9"},"PeriodicalIF":0.0,"publicationDate":"2006-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26040355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the biology of X-linked diseases.","authors":"Amparo Chabás, Rudolf Happle","doi":"10.1111/j.1651-2227.2006.tb02382.x","DOIUrl":"10.1111/j.1651-2227.2006.tb02382.x","url":null,"abstract":"","PeriodicalId":76973,"journal":{"name":"Acta paediatrica (Oslo, Norway : 1992). Supplement","volume":"95 451","pages":"9-10"},"PeriodicalIF":0.0,"publicationDate":"2006-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26041610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use of scoring systems in patients with haematological malignancy.","authors":"Derralynn A Hughes","doi":"10.1080/08035320600618866","DOIUrl":"https://doi.org/10.1080/08035320600618866","url":null,"abstract":"<p><strong>Unlabelled: </strong>The utility of predictive systems in patients with haematological malignancy stems both from the heterogeneity of disease presentation and from the inherent disadvantages of therapy. There is an acute morbidity and mortality associated with chemotherapy and bone marrow transplantation, a need for long term follow-up, the possibility of treatment failure and the issue of cost. In general, the value of a scoring system is in its ability to quantify disease burden, classify patient subgroups and predict disease course. Successful scoring systems are disease-specific, have been validated in an independent population and are useful in different countries, centres and individuals. There should be good discrimination of poorly responsive and optimally responsive populations and a high rate of prediction of the disease course for individual patients. Optimal utility should be provided by a few variables which are independent, highly predictive and easy to obtain. Other considerations include economic evaluation and adaptation for population changes over time.</p><p><strong>Conclusion: </strong>Experience gained from the use of staging and scoring systems in haematology provides useful insights into their potential use in Fabry disease and other lysosomal storage diseases. Such systems may help to predict whom to treat, when to treat and what response is likely to be achieved.</p>","PeriodicalId":76973,"journal":{"name":"Acta paediatrica (Oslo, Norway : 1992). Supplement","volume":"95 451","pages":"47-51"},"PeriodicalIF":0.0,"publicationDate":"2006-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/08035320600618866","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26039884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabry disease and vascular risk factors: future strategies for patient-based studies and the knockout murine model.","authors":"David F Moore,&nbsp;Monique P Gelderman,&nbsp;Steven R Fuhrmann,&nbsp;Raphael Schiffmann,&nbsp;Roscoe O Brady,&nbsp;Ehud Goldin","doi":"10.1080/08035320600618932","DOIUrl":"https://doi.org/10.1080/08035320600618932","url":null,"abstract":"<p><strong>Unlabelled: </strong>Fabry disease is secondary to deficiency of the lysosomal enzyme alpha-galactosidase A, leading to altered glycosphingolipid metabolism and accumulation that is often associated with endothelial dysfunction. Current evidence suggests that there is impairment of the vascular nitric oxide pathway, with abnormalities evident in the cerebral circulation and in the dermal vasculature of patients with Fabry disease. Some of these findings have been confirmed in a mouse model of Fabry disease. The murine model, however, allows investigation of Fabry disease at a non-clinical level and a near complete investigation of biological processes within an affected tissue. This is of particular utility in allowing gene expression analysis of clinically inaccessible tissues such as the aorta.</p><p><strong>Conclusion: </strong>Future developments in array technology for proteins and DNA single nucleotide polymorphism analysis, together with gene expression microarray analysis, may open a new chapter in our understanding of the biology of lysosomal storage disorders.</p>","PeriodicalId":76973,"journal":{"name":"Acta paediatrica (Oslo, Norway : 1992). Supplement","volume":"95 451","pages":"69-71"},"PeriodicalIF":0.0,"publicationDate":"2006-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/08035320600618932","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26039888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased carotid intima-media thickness in the absence of atherosclerotic plaques in an adult population with Fabry disease.","authors":"Frédéric Barbey,&nbsp;Noureddine Brakch,&nbsp;Ales Linhart,&nbsp;Xavier Jeanrenaud,&nbsp;Thomas Palecek,&nbsp;Jan Bultas,&nbsp;Michel Burnier,&nbsp;Daniel Hayoz","doi":"10.1080/08035320600618924","DOIUrl":"https://doi.org/10.1080/08035320600618924","url":null,"abstract":"<p><strong>Aim: </strong>Fabry disease is considered primarily as a progressive small vessel disease, with ischaemic degenerative lesions involving the kidneys, brain and heart. Macrovascular involvement in male patients includes an accelerated wall hypertrophy of the radial artery and a thickening of the intima-media of the common carotid artery. The aim of this study is to evaluate the prevalence and severity of carotid artery atherosclerosis in hemizygous and heterozygous patients with Fabry disease, compared with a matched control population.</p><p><strong>Methods: </strong>The common carotid artery intima-media thickness (IMT) of 53 patients with Fabry disease (24 men, 29 women) was measured by high-definition ultrasonography, and the presence or absence of atherosclerotic plaques reported. Results were compared with those of 120 age-matched healthy individuals (83 men, 37 women).</p><p><strong>Results: </strong>The common carotid artery IMT was increased to the same extent in male and female patients with Fabry disease (706+/-211 microm and 749+/-395 microm, respectively) compared with that of the control population (614+/-113 microm). In the Fabry population, IMT did not correlate with either systolic blood pressure or with renal function (plasma creatinine). In the control population, only systolic blood pressure was positively and significantly correlated with IMT. Atherosclerotic plaques in the common carotid artery were not observed in any patient with Fabry disease, whereas 34% of the control population had carotid artery plaques, as evidenced by focal non-homogeneous intima-media thickening greater than 1.2 mm.</p><p><strong>Conclusion: </strong>This study presents evidence of a major increase in common carotid artery IMT, both in hemizygous and heterozygous patients with Fabry disease, in the absence of focal atherosclerotic plaques. These results suggest that the conduit arteries may be protected from atherosclerosis in Fabry disease.</p>","PeriodicalId":76973,"journal":{"name":"Acta paediatrica (Oslo, Norway : 1992). Supplement","volume":"95 451","pages":"63-8"},"PeriodicalIF":0.0,"publicationDate":"2006-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26039887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysosomal dysfunction, cellular pathology and clinical symptoms: basic principles.","authors":"Arnold J J Reuser,&nbsp;Maarten R Drost","doi":"10.1080/08035320600618957","DOIUrl":"https://doi.org/10.1080/08035320600618957","url":null,"abstract":"<p><strong>Unlabelled: </strong>Between 40 and 50 lysosomal storage disorders are known at present. Fine details of the pathogenic process involved are in general not known. This overview highlights the basic principles of lysosomal pathogenesis and the clinical consequences of defective genes involved in lysosomal functions. The subject is discussed in the context of the possibility of prevention and reversal of cellular and organ damage by enzyme replacement therapy. Also presented is a mechanical model for the muscle pathology observed in Pompe disease. Direct mechanical effects of the non-contractile inclusions - glycogen-loaded lysosomes - seem to be a key factor in the loss of force during both early and late stages of the disease.</p><p><strong>Conclusion: </strong>Each lysosomal storage disorder and each patient with a given lysosomal disorder has unique molecular, pathological and clinical features. But, the order of pathological events is largely the same. Mutations in a gene cause lysosomal dysfunction which, in turn, results in cellular pathology affecting organ structure and function. Clinical symptoms are the ultimate manifestation. The reversibility of symptoms with enzyme replacement therapy will vary according to the disease, as well as the nature and stage of organ pathology.</p>","PeriodicalId":76973,"journal":{"name":"Acta paediatrica (Oslo, Norway : 1992). Supplement","volume":"95 451","pages":"77-82"},"PeriodicalIF":0.0,"publicationDate":"2006-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/08035320600618957","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26039890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pattern of inheritance of X-linked traits is not dominant or recessive, just X-linked.","authors":"William B Dobyns","doi":"10.1111/j.1651-2227.2006.tb02383.x","DOIUrl":"10.1111/j.1651-2227.2006.tb02383.x","url":null,"abstract":"<p><strong>Unlabelled: </strong>Our modern concepts of genetic inheritance originated nearly a century ago. Early concepts of dominant and recessive inheritance were developed in insects and were subsequently applied to sex-linked inheritance in mammals. Years of clinical experience, however, suggest that the modern-day rules for X-linked dominant and recessive diseases do not explain why so many female carriers of X-linked 'recessive' disorders have an abnormal phenotype. In a review of 32 X-linked diseases we revealed an unexpectedly high degree of intermediate disease penetrance in females that cannot be explained by existing concepts. We recommend that the terms 'dominant' and recessive' be abandoned and that these disorders be referred to as X-linked. In this review we will present modified rules for X-linked inheritance and propose hypotheses related to the potential mechanisms that may explain differences in disease expression in females.</p><p><strong>Conclusion: </strong>Past assumptions regarding factors that may affect phenotype in heterozygous females do not capture the extraordinarily variable expressivity of X-linked disorders in females and need to be revisited.</p>","PeriodicalId":76973,"journal":{"name":"Acta paediatrica (Oslo, Norway : 1992). Supplement","volume":"95 451","pages":"11-5"},"PeriodicalIF":0.0,"publicationDate":"2006-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26041611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease manifestations and X inactivation in heterozygous females with Fabry disease.","authors":"Esther M Maier, Stephanie Osterrieder, Catharina Whybra, Markus Ries, Andreas Gal, Michael Beck, Adelbert A Roscher, Ania C Muntau","doi":"10.1111/j.1651-2227.2006.tb02386.x","DOIUrl":"10.1111/j.1651-2227.2006.tb02386.x","url":null,"abstract":"<p><strong>Aim: </strong>Fabry disease is an X-linked lysosomal storage disorder characterized by an accumulation of neutral glycosphingolipids in multiple organ systems caused by alpha-galactosidase A deficiency due to mutations in the GLA gene. The majority of heterozygous females show the characteristic signs and symptoms of the disease, and some of them are severely affected. The current hypothesis for the occurrence of disease manifestations in females is skewed X inactivation favouring the mutant GLA allele.</p><p><strong>Method: </strong>We analyzed the patterns of X inactivation in the leukocytes of 28 biochemically and genetically characterized symptomatic Fabry disease heterozygotes and their correlation with clinical and biochemical disease expression.</p><p><strong>Results: </strong>X inactivation patterns in symptomatic females who are heterozygous for Fabry disease did not differ from those of female controls of the same age (p = 0.669). Thirteen (46%) of the 28 females with Fabry disease showed random X inactivation, ten (36%) moderate skewing, and five (18%) highly skewed X inactivation. Segregation analysis was performed in the families of six females who had highly or moderately skewed X inactivation. In four of these females, skewing favoured the wild-type GLA allele and in the other two skewing favoured the mutant allele. Patterns of X inactivation or the extent of skewing were not related to the severity of clinical manifestations or to residual enzyme activity.</p><p><strong>Conclusion: </strong>In this study we provide evidence that heterozygous females with Fabry disease show random X inactivation. Our data do not support the hypothesis that the occurrence and severity of disease manifestations in the majority of Fabry heterozygotes are related to skewed X inactivation.</p>","PeriodicalId":76973,"journal":{"name":"Acta paediatrica (Oslo, Norway : 1992). Supplement","volume":"95 451","pages":"30-8"},"PeriodicalIF":0.0,"publicationDate":"2006-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26039881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}