Abstract:
:Urea cycle disorders (UCDs) are inborn errors of ammonia detoxification/arginine synthesis due to defects affecting the catalysts of the Krebs-Henseleit cycle (five core enzymes, one activating enzyme and one mitochondrial ornithine/citrulline antiporter) with an estimated incidence of 1:8.000. Patients present with hyperammonemia either shortly after birth (~50%) or, later at any age, leading to death or to severe neurological handicap in many survivors. Despite the existence of effective therapy with alternative pathway therapy and liver transplantation, outcomes remain poor. This may be related to underrecognition and delayed diagnosis due to the nonspecific clinical presentation and insufficient awareness of health care professionals because of disease rarity. These guidelines aim at providing a trans-European consensus to: guide practitioners, set standards of care and help awareness campaigns. To achieve these goals, the guidelines were developed using a Delphi methodology, by having professionals on UCDs across seven European countries to gather all the existing evidence, score it according to the SIGN evidence level system and draw a series of statements supported by an associated level of evidence. The guidelines were revised by external specialist consultants, unrelated authorities in the field of UCDs and practicing pediatricians in training. Although the evidence degree did hardly ever exceed level C (evidence from non-analytical studies like case reports and series), it was sufficient to guide practice on both acute and chronic presentations, address diagnosis, management, monitoring, outcomes, and psychosocial and ethical issues. Also, it identified knowledge voids that must be filled by future research. We believe these guidelines will help to: harmonise practice, set common standards and spread good practices with a positive impact on the outcomes of UCD patients.
journal_name
Orphanet J Rare Disjournal_title
Orphanet journal of rare diseasesauthors
Häberle J,Boddaert N,Burlina A,Chakrapani A,Dixon M,Huemer M,Karall D,Martinelli D,Crespo PS,Santer R,Servais A,Valayannopoulos V,Lindner M,Rubio V,Dionisi-Vici Cdoi
10.1186/1750-1172-7-32subject
Has Abstractpub_date
2012-05-29 00:00:00pages
32issn
1750-1172pii
1750-1172-7-32journal_volume
7pub_type
杂志文章,评审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:Orphan medicinal products (OMPs) are intended for the diagnosis, prevention, management or treatment of rare diseases (RDs). Each RD affects only a small fraction of the population, and therefore, historically, industry hesitated to undertake relevant research and development (R&D). In response, the governme...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1224-0
更新日期:2019-11-04 00:00:00
abstract:BACKGROUND:Prader-Willi-Syndrome (PWS) is characterized by hypothalamic-pituitary dysfunction. Recent research suggests starting growth hormone-treatment (GHT) as soon as possible. The aim of this study is to analyze possible differences in auxological parameters, carbohydrate and lipid metabolism between two groups of...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-01527-0
更新日期:2020-10-12 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:OBJECTIVE:NUT midline carcinoma (NMC), a rare type of squamous cell carcinoma, is genetically characterised by NUT midline carcinoma family member 1 (NUTM1) gene rearrangement. NMC can arise from the lungs; however, there is no standard for the management of primary pulmonary NMC. This study aimed to confirm the clinic...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-01449-x
更新日期:2020-07-10 00:00:00
abstract:BACKGROUND:Müllerian aplasia (MA) characterized by congenital loss of functional uterus and vagina is one of the most difficult disorders of female reproductive health. Despite of growing interest in this research field, the cause of the disorder for the majority of patients is still unknown. A recent report of partial...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-6-53
更新日期:2011-08-02 00:00:00
abstract:BACKGROUND:Congenital tuberculosis is rare and carries a high mortality rate. Our objective was to summarize the current experience of the diagnosis and treatment of patients with congenital tuberculosis. METHODS:In total, 73 reported cases of congenital tuberculosis published in Chinese and 19 patients with congenita...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-019-1101-x
更新日期:2019-06-10 00:00:00
abstract:BACKGROUND:A study was designed to identify the source of fever in a patient with post-polycythemia myelofibrosis, associated with clonal Janus Kinase 2 (JAK2) mutation involving duplication of exon 12. The patient presented with 1-2 day long self-limited periodic episodes of high fever that became more frequent as the...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-015-0298-6
更新日期:2015-06-30 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:Inherited Factor XIII deficiency (FXIIID) is one of the most severe and under-diagnosed rare bleeding disorders. Only 5 large deletions involving one or more exons in F13A1 have been reported, and lacking of multiplex ligation-dependent probe amplification (MLPA) assay might underestimate the copy number var...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1144-z
更新日期:2019-07-24 00:00:00
abstract::Patients with TARDBP mutations have so far been classified as ALS, sometimes with frontal lobe dysfunction. A 66-year-old patient progressively developed a severe sensory disorder, followed by a motor disorder, which evolved over nine years. Symptoms started in the left hand and slowly involved the four limbs. Investi...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-6-4
更新日期:2011-02-05 00:00:00
abstract:BACKGROUND:Urea cycle disorders (UCDs) are a group of rare inherited metabolic disorders. Affected individuals often present with hyperammonemic encephalopathy (HE) and have an increased risk of severe neurologic disease and early death. The study aims to provide epidemiologic data and to describe the disease manifesta...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-017-0661-x
更新日期:2017-06-15 00:00:00
abstract::Glutamine synthetase (GS) is ubiquitously expressed in mammalian organisms and is a key enzyme in nitrogen metabolism. It is the only known enzyme capable of synthesising glutamine, an amino acid with many critical roles in the human organism. A defect in GLUL, encoding for GS, leads to congenital systemic glutamine d...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-7-48
更新日期:2012-07-25 00:00:00
abstract:BACKGROUND:Segmental progeroid syndromes are a heterogeneous group of rare and often severe genetic disorders that have been studied since the twentieth century. These progeroid syndromes are defined as segmental because only some of the features observed during natural aging are accelerated. METHODS:Since 2015, the M...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1189-z
更新日期:2019-12-11 00:00:00
abstract:BACKGROUND:Acid sphingomyelinase deficiency (ASMD), due to mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene, is divided into infantile neurovisceral ASMD (Niemann-Pick type A), chronic neurovisceral ASMD (intermediate form, Niemann-Pick type A/B) and chronic visceral ASMD (Niemann-Pick type B). We conduc...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1029-1
更新日期:2019-02-22 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::Oculocutaneous albinism (OCA) is a group of inherited disorders of melanin biosynthesis characterized by a generalized reduction in pigmentation of hair, skin and eyes. The prevalence of all forms of albinism varies considerably worldwide and has been estimated at approximately 1/17,000, suggesting that about 1 in 70 ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/1750-1172-2-43
更新日期:2007-11-02 00:00:00
abstract::Since its enactment in 2000, the European Orphan Medicinal Products Regulation has allowed the review and approval of approaching 70 treatments for some 55 different conditions in Europe. Success does not come without a price, however. Many of these so-called "orphan drugs" have higher price points than treatments for...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-7-74
更新日期:2012-09-26 00:00:00
abstract:BACKGROUND:Stiff Person Syndrome (SPS) is a rare autoimmune movement disorder characterized by the presence of autoantibodies specific to the smaller isoform of glutamate decarboxylase (GAD65). A pathological role of these antibodies has been suggested by their capacity to inhibit GAD65 enzyme activity and by the obser...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-8-82
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abstract:BACKGROUND:Hypophosphatasia (HPP) is a rare inborn error of metabolism that results from dysfunction of the tissue non-specific alkaline phosphatase enzyme. Its manifestations are extremely variable, ranging from early lethality to disease limited to the dentition. The disease is life-threatening when manifesting withi...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-018-0866-7
更新日期:2018-07-16 00:00:00
abstract:BACKGROUND:Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-015-0284-z
更新日期:2015-05-28 00:00:00
abstract:BACKGROUND:Osteogenesis Imperfecta (OI) is a rare genetic disorder involving bone fragility. OI patients typically suffer from numerous fractures, skeletal deformities, shortness of stature and hearing loss. The disorder is characterised by genetic and clinical heterogeneity. Pathogenic variants in more than 20 differe...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-020-01404-w
更新日期:2020-05-27 00:00:00
abstract:BACKGROUND:Rare diseases (RDs) are often neglected because they affect a small percentage of the population (6-8 %), which makes research and development of new therapies challenging processes. Easy access to high-quality samples and associated clinical data is therefore a key prerequisite for biomedical research. In t...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-016-0527-7
更新日期:2016-10-24 00:00:00
abstract:BACKGROUND:Alleviating the burden of rare diseases requires research into new diagnostic and therapeutic strategies. We undertook a systematic review to identify and compare the impact of stand-alone registries, registries with biobanks, and rare disease biobanks on research outcomes in rare diseases. METHODS:A system...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-018-0942-z
更新日期:2018-11-12 00:00:00
abstract:OBJECTIVE:Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disease with many manifestations, and it involves any organ. In this study, we report a TSC patient with new type skin lesions. METHODS:A 7-month-old TSC boy with multiple cutaneous nodules was admitted in our hospital. We collected the cl...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-01396-7
更新日期:2020-06-12 00:00:00
abstract:BACKGROUND:The aim of our study is to study the association between eye lesions in Hereditary Hemorrhagic Telangiectasia (HHT) and other signs of the disease, as well as to characterize its genetics. METHODS:A cross-sectional study was conducted of a cohort of 206 patients studied in the HHT Unit of Hospital de Sierra...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-01433-5
更新日期:2020-06-29 00:00:00
abstract:BACKGROUND:Many genetic diseases are due to defects in protein trafficking where the mutant protein is recognized by the quality control systems, retained in the endoplasmic reticulum (ER), and degraded by the proteasome. In many cases, the mutant protein retains function if it can be trafficked to its proper cellular ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-8-11
更新日期:2013-01-14 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: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:This study was conducted to identify potential biomarkers that could be used to evaluate disease progression and monitor responses to enzyme replacement therapy (ERT) in patients with mucopolysaccharidosis (MPS) IVA. METHODS:Levels of 88 candidate biomarkers were compared in plasma samples from 50 healthy c...
journal_title:Orphanet journal of rare diseases
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/1750-1172-6-84
更新日期:2011-12-16 00:00:00