Abstract:
BACKGROUND:X-linked Duchenne muscular dystrophy (DMD), the most frequent human hereditary skeletal muscle myopathy, inevitably leads to progressive dilated cardiomyopathy. We assessed the effect and safety of a combined treatment with the ACE-inhibitor enalapril and the β-blocker metoprolol in a German cohort of infantile and juvenile DMD patients with preserved left ventricular function. METHODS TRIAL DESIGN:Sixteen weeks single-arm open run-in therapy with enalapril and metoprolol followed by a two-arm 1:1 randomized double-blind placebo-controlled treatment in a multicenter setting. INCLUSION CRITERIA:DMD boys aged 10-14 years with left ventricular fractional shortening [LV-FS] ≥ 30% in echocardiography. Primary endpoint: time from randomization to first occurrence of LV-FS < 28%. Secondary: changes of a) LV-FS from baseline, b) blood pressure, c), heart rate and autonomic function in ECG and Holter-ECG, e) cardiac biomarkers and neurohumeral serum parameters, f) quality of life, and g) adverse events. RESULTS:From 3/2010 to 12/2013, 38 patients from 10 sites were centrally randomized after run-in, with 21 patients continuing enalapril and metoprolol medication and 17 patients receiving placebo. Until end of study 12/2015, LV-FS < 28% was reached in 6/21 versus 7/17 patients. Cox regression adjusted for LV-FS after run-in showed a statistically non-significant benefit for medication over placebo (hazard ratio: 0.38; 95% confidence interval: 0.12 to 1.22; p = 0.10). Analysis of secondary outcome measures revealed a time-dependent deterioration of LV-FS with no statistically significant differences between the two study arms. Blood pressure, maximal heart rate and mean-NN values were significantly lower at the end of open run-in treatment compared to baseline. Outcome analysis 19 months after randomization displayed significantly lower maximum heart rate and higher noradrenalin and renin values in the intervention group. No difference between treatments was seen for quality of life. As a single, yet important adverse event, the reversible deterioration of walking abilities of one DMD patient during the run-in period was observed. CONCLUSIONS:Our analysis of enalapril and metoprolol treatment in DMD patients with preserved left ventricular function is suggestive to delay the progression of the intrinsic cardiomyopathy to left ventricular failure, but did not reach statistical significance, probably due to insufficient sample size. CLINICAL TRIAL REGISTRATION:DRKS-number 00000115, EudraCT-number 2009-009871-36.
journal_name
Orphanet J Rare Disjournal_title
Orphanet journal of rare diseasesauthors
Dittrich S,Graf E,Trollmann R,Neudorf U,Schara U,Heilmann A,von der Hagen M,Stiller B,Kirschner J,Pozza RD,Müller-Felber W,Weiss K,von Au K,Khalil M,Motz R,Korenke C,Lange M,Wilichowski E,Pattathu J,Ebinger F,Wiecdoi
10.1186/s13023-019-1066-9subject
Has Abstractpub_date
2019-05-10 00:00:00pages
105issue
1issn
1750-1172pii
10.1186/s13023-019-1066-9journal_volume
14pub_type
杂志文章,随机对照试验abstract:BACKGROUND:FBLN5-related cutis laxa (CL) is a rare disorder that involves elastic fiber-enriched tissues and is characterized by lax skin and variable systemic involvement such as pulmonary emphysema, arterial involvement, inguinal hernias, hollow viscus diverticula and pyloric stenosis. This type of CL follows mostly ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-021-01696-6
更新日期:2021-01-28 00:00:00
abstract:BACKGROUND:Morquio A syndrome (or mucopolysaccharidosis IVa) is an ultra-rare multi-organ disease, resulting in significantly impaired functional capacity, mobility and quality of life (QoL). METHODS:This patient-reported outcomes survey evaluated the global burden of Morquio A among adults (≥18 years, N = 27) and chi...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-9-32
更新日期:2014-03-07 00:00:00
abstract:BACKGROUND:Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder characterized by sclerosing leukoencephalopathy and multifocal bone cysts, caused by a loss-of-function mutation of either DAP12 or TREM2. TREM2 and DAP12 constitute a receptor/adaptor signaling complex expressed exclusively on osteoclasts, den...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-9-68
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND:Glycogenosis type II or Pompe disease is an autosomal-recessive lysosomal storage disease due to mutations in the gene encoding acid alpha-glucosidase (GAA), an enzyme required for lysosomal glycogen degradation. The disease predominantly affects the skeletal and respiratory muscles but there is growing evid...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-9-17
更新日期:2014-02-05 00:00:00
abstract:BACKGROUND:Costello syndrome (CS) and cardio-facio-cutaneous syndrome (CFCS) belong to the RASopathies, a group of neurodevelopmental disorders with skeletal anomalies. Due to their rarity, the characterization of the musculo-skeletal phenotype in both disorders has been poorly characterized. PATIENTS AND METHODS:Here...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-021-01674-y
更新日期:2021-01-22 00:00:00
abstract:BACKGROUND:Charcot-Marie-Tooth type 1A disease (CMT1A) is a rare orphan inherited neuropathy caused by an autosomal dominant duplication of a gene encoding for the structural myelin protein PMP22, which induces abnormal Schwann cell differentiation and dysmyelination, eventually leading to axonal suffering then loss an...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/s13023-014-0199-0
更新日期:2014-12-18 00:00:00
abstract:BACKGROUND:There are an established and growing number of Mendelian genetic causes for chronic kidney disease (CKD) in adults, though estimates of prevalence have been speculative. The CKD Queensland (CKD.QLD) registry enables partial clarification of this through the study of adults with CKD receiving nephrology care ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-9-98
更新日期:2014-06-30 00:00:00
abstract::Among the challenges confronting patients with rare diseases is a dearth of treatment options. The development of safe and effective new therapies is hampered by challenges associated with conducting clinical trials in small populations. In this article, we describe how the Duchenne muscular dystrophy community-led by...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-015-0281-2
更新日期:2015-06-24 00:00:00
abstract:BACKGROUND:Pigmentary mosaicism is a term that describes varied patterns of pigmentation in the skin caused by genetic heterogeneity of the skin cells. In a substantial number of cases, pigmentary mosaicism is observed alongside extracutaneous abnormalities typically involving the central nervous system and the musculo...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-018-0778-6
更新日期:2018-03-05 00:00:00
abstract::Monogenic autoinflammatory diseases are a group of hereditary disorders characterized by a clinical and biological inflammatory syndrome in which there is little or no evidence of autoimmunity. The discovery of the first causative gene in 1997 was rapidly followed by the identification of many others from the same gro...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/1750-1172-8-162
更新日期:2013-10-16 00:00:00
abstract::Joubert syndrome (JS) and related disorders (JSRD) are a group of developmental delay/multiple congenital anomalies syndromes in which the obligatory hallmark is the molar tooth sign (MTS), a complex midbrain-hindbrain malformation visible on brain imaging, first recognized in JS. Estimates of the incidence of JSRD ra...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/1750-1172-5-20
更新日期:2010-07-08 00:00:00
abstract:BACKGROUND:Phosphomannomutase deficiency (PMM2-CDG) is the most frequent congenital disorder of glycosylation. The cerebellum is nearly always affected in PMM2-CDG patients, a cerebellar atrophy progression is observed, and cerebellar dysfunction is their main daily functional limitation. Different therapeutic agents a...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-015-0358-y
更新日期:2015-10-26 00:00:00
abstract:BACKGROUND:Most patients with alpha-1 antitrypsin deficiency remain undiagnosed and therefore do not benefit from current therapies or become eligible for research studies of new treatments under development. Improving the detection rate for AATD is therefore a high priority for the Alpha-1 Foundation. A workshop was h...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-020-01352-5
更新日期:2020-04-19 00:00:00
abstract:BACKGROUND:Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder characterized by wide clinical, genetic and pathomechanistic heterogeneity. Recently, the gene encoding peripheral myelin protein 2 (PMP2) was identified as a novel cause for CMT neuropathy with three mutations that structu...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1162-x
更新日期:2019-08-14 00:00:00
abstract::Biliary atresia (BA) is a rare disease characterised by a biliary obstruction of unknown origin that presents in the neonatal period. It is the most frequent surgical cause of cholestatic jaundice in this age group. BA occurs in approximately 1/18,000 live births in Western Europe. In the world, the reported incidence...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/1750-1172-1-28
更新日期:2006-07-26 00:00:00
abstract:BACKGROUND:The objective of this study was to assess the potential impact of the implementation of multiple-criteria decision analysis (MCDA) on the Polish pricing and reimbursement (P&R) process with regard to orphan drugs. METHODS:A four step approach was designed. Firstly, a systematic literature review was conduct...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-016-0388-0
更新日期:2016-03-10 00:00:00
abstract::Warburg micro syndrome (WARBM) is a genetic heterogeneous disease characterized by microcephaly, intellectual disability, brain, ocular, and endocrine anomalies. WARBM1-4 can be caused by biallelic mutations of the RAB3GAP1 (RAB3 GTPase-activating protein 1), RAB3GAP2, RAB18 (RAS-associated protein RAB18), or TBC1D20 ...
journal_title:Orphanet journal of rare diseases
pub_type: 信件
doi:10.1186/s13023-014-0113-9
更新日期:2014-10-21 00:00:00
abstract:BACKGROUND:Hepatic macrophage (Kupffer cell) hyperplasia is often described in Wilson's disease (WD). In many liver diseases, Kupffer cell activation is related to disease severity, liver function, and fibrosis but the importance in WD is unknown. Kupffer cell activation can be assessed by the P-concentration of solubl...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-018-0910-7
更新日期:2018-09-21 00:00:00
abstract:BACKGROUND:Von Hippel-Lindau (VHL) disease is a multi-systemic hereditary disease associated with several benign and malignant tumor entities, including clear cell renal cell carcinoma (ccRCC). Since ccRCCs grow slowly, nephron sparing surgery is typically performed at a tumor diameter of 3-4 cm before the tumor metast...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1206-2
更新日期:2019-10-28 00:00:00
abstract:BACKGROUND:Sporadic inclusion body myositis (sIBM) is the most prevalent muscle disease in elderly people, affecting the daily activities. sIBM is progressive with unknown cause and without effective treatment. In 2015, sIBM was classified as an intractable disease by the Japanese government, and the treatment cost was...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1122-5
更新日期:2019-06-26 00:00:00
abstract::IgA pemphigus is an exceedingly rare autoimmune blistering disorder, caused by IgA autoantibodies against desmosomal proteins. No treatment option has been found to be universally effective. The disease is often recalcitrant to oral steroids and immunosuppressants. Here, we describe the use of systemic retinoids for t...
journal_title:Orphanet journal of rare diseases
pub_type: 信件
doi:10.1186/s13023-018-0899-y
更新日期:2018-09-18 00:00:00
abstract:BACKGROUND:Oligosaccharidoses are storage disorders due to enzymatic defects involved in the breakdown of the oligosaccharidic component of glycosylated proteins. The defect cause the accumulation of oligosaccharides (OS) and, depending on the lacking enzyme, results in characteristic profiles which are helpful for the...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-01662-8
更新日期:2021-01-09 00:00:00
abstract:OBJECTIVE:To investigate differences in cardiac manifestations of patients affected by laminopathy, according to the presence or absence of neuromuscular involvement at presentation. METHODS:We prospectively analyzed 40 consecutive patients with a diagnosis of laminopathy followed at a single centre between 1998 and 2...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1245-8
更新日期:2019-11-19 00:00:00
abstract:BACKGROUND:Rubinstein-Taybi syndrome (RTS) is a rare, congenital, plurimalformative, and neurodevelopmental disorder. Previous studies have reported that large deletions contribute to more severe RTS phenotypes than those caused by CREBBP point mutations, suggesting a concurrent pathogenetic role of flanking genes, typ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-01378-9
更新日期:2020-04-22 00:00:00
abstract:BACKGROUND:Mucopolysaccharidosis type I (MPS I) is a debilitating hereditary disease characterized by alpha-L-iduronidase (IDUA) deficiency and consequent inability to degrade glycosaminoglycans. The pathological accumulation of glycosaminoglycans systemically results in severe mental retardation and multiple organ dys...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-017-0649-6
更新日期:2017-06-08 00:00:00
abstract::An amendment to this paper has been published and can be accessed via the original article. ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,已发布勘误
doi:10.1186/s13023-020-01464-y
更新日期:2020-08-05 00:00:00
abstract:BACKGROUND:Primary Ciliary Dyskinesia (PCD) diagnosis relies on a combination of tests which may include (a) nasal Nitric Oxide (nNO), (b) High Speed Video Microscopy (HSVM) and (c) Transmission Electron Microscopy (TEM). There is variability in the availability of these tests and lack of universal agreement whether di...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1116-3
更新日期:2019-06-13 00:00:00
abstract:BACKGROUND:Treatment of phenylketonuria (PKU) with sapropterin dihydrochloride in responsive patients from an early age can have many advantages for the patient over dietary restriction alone. Accordingly, approval of sapropterin in the European Union was extended in 2015 to include patients aged 0-4 years, bringing th...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-018-0911-6
更新日期:2018-09-29 00:00:00
abstract:BACKGROUND:It is unknown whether the neonatal tetrahydrobiopterin (BH4) loading test is adequate to diagnose long-term BH4 responsiveness in PKU. Therefore we compared the predictive value of the neonatal (test I) versus the 48-h BH4 loading test (test II) and long-term BH4 responsiveness. METHODS:Data on test I (>199...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-016-0394-2
更新日期:2016-01-29 00:00:00
abstract:BACKGROUND:The Dandy-Walker malformation (DWM) is one of the commonest congenital cerebellar defects, and can be associated with multiple congenital anomalies and chromosomal syndromes. The occurrence of overlapping 3q deletions including the ZIC1 and ZIC4 genes in few patients, along with data from mouse models, have ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-8-75
更新日期:2013-05-16 00:00:00