Abstract:
BACKGROUND:Lysinuric protein intolerance (LPI) is a rare metabolic disease resulting from recessive-inherited mutations in the SLC7A7 gene encoding the cationic amino-acids transporter subunit y+LAT1. The disease is characterised by protein-rich food intolerance with secondary urea cycle disorder, but symptoms are heterogeneous ranging from infiltrative lung disease, kidney failure to auto-immune complications. This retrospective study of all cases treated at Necker Hospital (Paris, France) since 1977 describes LPI in both children and adults in order to improve therapeutic management. RESULTS:Sixteen patients diagnosed with LPI (12 males, 4 females, from 9 families) were followed for a mean of 11.4 years (min-max: 0.4-37.0 years). Presenting signs were failure to thrive (n = 9), gastrointestinal disorders (n = 2), cytopenia (n = 6), hyperammonemia (n = 10) with acute encephalopathy (n = 4) or developmental disability (n = 3), and proteinuria (n = 1). During follow-up, 5 patients presented with acute hyperammonemia, and 8 presented with developmental disability. Kidney disease was observed in all patients: tubulopathy (11/11), proteinuria (4/16) and kidney failure (7/16), which was more common in older patients (mean age of onset 17.7 years, standard deviation 5.33 years), with heterogeneous patterns including a lupus nephritis. We noticed a case of myocardial infarction in a 34-year-old adult. Failure to thrive and signs of haemophagocytic-lymphohistiocytosis were almost constant. Recurrent acute pancreatitis occurred in 2 patients. Ten patients developed an early lung disease. Six died at the mean age of 4 years from pulmonary alveolar proteinosis. This pulmonary involvement was significantly associated with death. Age-adjusted plasma lysine concentrations at diagnosis showed a trend toward increased values in patients with a severe disease course and premature death (Wilcoxon p = 0.08; logrank, p = 0.17). Age at diagnosis was a borderline predictor of overall survival (logrank, p = 0.16). CONCLUSIONS:As expected, early pulmonary involvement with alveolar proteinosis is frequent and severe, being associated with an increased risk of death. Kidney disease frequently occurs in older patients. Cardiovascular and pancreatic involvement has expanded the scope of complications. A borderline association between increased levels of plasma lysine and poorer outome is suggested. Greater efforts at prevention are warranted to optimise the long-term management in these patients.
journal_name
Orphanet J Rare Disjournal_title
Orphanet journal of rare diseasesauthors
Mauhin W,Habarou F,Gobin S,Servais A,Brassier A,Grisel C,Roda C,Pinto G,Moshous D,Ghalim F,Krug P,Deltour N,Pontoizeau C,Dubois S,Assoun M,Galmiche L,Bonnefont JP,Ottolenghi C,de Blic J,Arnoux JB,de Lonlay Pdoi
10.1186/s13023-016-0550-8subject
Has Abstractpub_date
2017-01-05 00:00:00pages
3issue
1issn
1750-1172pii
10.1186/s13023-016-0550-8journal_volume
12pub_type
杂志文章abstract:BACKGROUND:Isovaleric aciduria (IVA), propionic aciduria (PA) and methylmalonic aciduria (MMA) are inherited organic acidurias (OAs) in which impaired organic acid metabolism induces hyperammonaemia arising partly from secondary deficiency of N-acetylglutamate (NAG) synthase. Rapid reduction in plasma ammonia is requir...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,多中心研究
doi:10.1186/s13023-016-0406-2
更新日期:2016-03-31 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:Inherited metabolic disorders (IMDs) are group of rare monogenic diseases, usually derived from reduced or absent activity in a single metabolic pathway. Most of the IMDs are inherited in an autosomal recessive manner. The incidence of IMDs varies from country to country and within different ethnic groups, b...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-01578-3
更新日期:2020-11-25 00:00:00
abstract:BACKGROUND:Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder, which is usually caused by de novo mutations in the MECP2 gene. More than 70% of the disease causing MECP2 mutations are eight recurrent C to T transitions, which almost exclusively arise on the paternally derived X chromosome. About 10...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/1750-1172-6-58
更新日期:2011-08-30 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: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: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
更新日期:2013-06-05 00:00:00
abstract:BACKGROUND:Imerslund-Gräsbeck syndrome (IGS) was described just over 50 years ago by Olga Imerslund and Ralph Gräsbeck and colleagues. IGS is caused by specific malabsorption of cobalamin (Cbl) due to bi-allelic mutations in either the cubilin gene (CUBN) or the human amnionless homolog (AMN). Mutations in the two gene...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-6-74
更新日期:2011-11-13 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:Huntington's disease (HD) is a devastating brain disorder with no effective treatment or cure available. The scarcity of brain tissue makes it hard to study changes in the brain and impossible to perform longitudinal studies. However, peripheral pathology in HD suggests that it is possible to study the disea...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-016-0475-2
更新日期:2016-08-01 00:00:00
abstract:BACKGROUND:The group of ELAC2-related encephalomyopathies is a recent addition to the rapidly growing heterogeneous mitochondrial disorders. RESULTS:We describe a highly inbred consanguineous Pakistani family with multiple affected children in 2 branches exhibiting moderately severe global developmental delay. Using h...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-016-0526-8
更新日期:2016-10-21 00:00:00
abstract::Taliglucerase alfa is an enzyme replacement therapy (ERT) approved for treatment of adult and paediatric patients with Type 1 Gaucher disease (GD) in several countries and the first plant cell-expressed recombinant therapeutic protein approved by the US Food and Drug Administration for humans. Here, we review the find...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-018-0776-8
更新日期:2018-02-23 00:00:00
abstract:BACKGROUND:Inherited epidermolysis bullosa (EB) comprises a highly heterogeneous group of rare diseases characterized by exacerbated skin and/or mucosal fragility and blister formation after minor mechanical trauma. Level of cleavage in the skin, clinical features with immunofluorescence antigen mapping and/or electron...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-016-0489-9
更新日期:2016-08-20 00:00:00
abstract:BACKGROUND:Many of the genetic childhood disorders leading to death in the pre- or neonatal period or during early childhood follow autosomal recessive modes of inheritance and bear specific challenges for genetic counseling and prenatal diagnostics. Parents are carriers but clinically unaffected, and diseases are rare...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-018-0763-0
更新日期:2018-01-26 00:00:00
abstract:BACKGROUND:Rare diseases are individually rare but globally affect around 6% of the population, and in over 70% of cases are genetically determined. Their rarity translates into a delayed diagnosis, with 25% of patients waiting 5 to 30 years for one. It is essential to raise awareness of patients and clinicians of exis...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-01493-7
更新日期:2020-08-12 00:00:00
abstract::The hyper-IgE syndromes are rare, complex primary immunodeficiencies characterized by clinical manifestation diversity, by particular susceptibility to staphylococcal and mycotic infections as well as by a heterogeneous genetic origin. Two distinct entities--the classical hyper-IgE syndrome which is inherited in an au...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/1750-1172-6-76
更新日期:2011-11-15 00:00:00
abstract:BACKGROUND:Approximately 20% of adrenoleukodystrophy (X-ALD) female carriers may develop clinical manifestations, typically consisting of progressive spastic gait, sensory deficits and bladder dysfunctions. A skewing in X Chromosome Inactivation (XCI), leading to the preferential expression of the X chromosome carrying...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-7-10
更新日期:2012-01-26 00:00:00
abstract::We report a male child with Oromandibular-limb hypogenesis (OMLH), the main features being bilateral sixth and seventh nerve palsies, limb anomalies and hypoplasia of the tongue. Additional features were shortness of the neck associated with torticollis. Radiographs of the cervical spine were non-contributory, but 3D ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-2-2
更新日期:2007-01-08 00:00:00
abstract:BACKGROUND:The small cell ovarian carcinoma of the hypercalcemic type (SCCOHT) which preferably affects young women during regenerative age represents a rare and aggressive form of ovarian tumors with poor prognosis and lacks an efficient therapy. METHODS AND RESULTS:In vitro chemotherapy testing in a fluorescence ass...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-014-0126-4
更新日期:2014-08-08 00:00:00
abstract:BACKGROUND:Lipodystrophy syndromes comprise a group of extremely rare and heterogeneous diseases characterized by a selective loss of adipose tissue in the absence of nutritional deprivation or catabolic state. Because of the rarity of each lipodystrophy subform, research in this area is difficult and international co-...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-1295-y
更新日期:2020-01-15 00:00:00
abstract:BACKGROUND:Fibrosarcomatous dermatofibrosarcoma protuberans (FS-DFSP) is a form of tumor progression of dermatofibrosarcoma protuberans (DFSP) with an increased risk of metastasis and recurrence. Few studies have compared the clinicopathological features of FS-DFSP and conventional DFSP (C-DFSP). OBJECTIVES:To better ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-021-01698-4
更新日期:2021-01-26 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:A pattern of major and minor congenital anomalies, facial dysmorphic features, and neurodevelopmental difficulties, including cognitive and social impairments has been reported in some children exposed to sodium valproate (VPA) during pregnancy. Recognition of the increased risks of in utero exposure to VPA ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1064-y
更新日期:2019-07-19 00:00:00
abstract:BACKGROUND:The needs and benefits of sharing health data to advance scientific research and improve clinical benefits have been well documented in recent years, specifically in the field of rare diseases where knowledge and expertise are limited and patient populations are geographically dispersed. Understanding what p...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1123-4
更新日期:2019-07-12 00:00:00
abstract::Microvillous inclusion disease (MVID) or microvillous atrophy is a congenital disorder of the intestinal epithelial cells that presents with persistent life-threatening watery diarrhea and is characterized by morphological enterocyte abnormalities. MVID manifests either in the first days of life (early-onset form) or ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/1750-1172-1-22
更新日期:2006-06-26 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::The original version of this article [1] unfortunately included an error to an author's name. Author Maja Di Rocco was erroneously presented as Maja DiRocco.The correct author name has been included in the author list of this Correction article and is already updated in the original article. ...
journal_title:Orphanet journal of rare diseases
pub_type: 已发布勘误
doi:10.1186/s13023-019-1096-3
更新日期:2019-05-23 00:00:00
abstract:BACKGROUND:Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare disease, characterized by the massive accumulation of triglyceride (TG) in multiple tissues, especially skeletal muscle, heart muscle and the coronary artery. TGCV is caused by mutation of adipose triglyceride lipase, which is an essential molecule ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-8-197
更新日期:2013-12-21 00:00:00
abstract:BACKGROUND:Epidermolysis bullosa acquisita (EBA) is an orphan autoimmune disease. Several clinical phenotypes have been described, but subepidermal blistering is characteristic of all variants. Limited data on clinical and immunopathological characteristics and treatment outcomes in EBA are available. To fill this gap,...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,meta分析
doi:10.1186/s13023-018-0896-1
更新日期:2018-09-04 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