6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/09/12

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Cooccurrence of Chorea-Acanthocytosis and Mesial Temporal Sclerosis: A Possible Role of Caudate Nucleus.

Case Rep Neurol Med. 2017;2017:2810925

Authors: Salari M, Lehn AC, Etemadifar M, Hejazi SA

Abstract
Chorea-acanthocytosis (ChAc) is an orphan disease, caused by mutations on chromosome 9. Epileptic seizures of mesial temporal origin can be a predominant symptom. We report on a 29-year-old woman with ChAc and bilateral MTS. Previously, few patients with coexisting ChAc and MTS were reported. The underlying pathophysiology is unknown, and further studies are needed.

PMID: 28884035 [PubMed]

A three-dimensional model of human lung development and disease from pluripotent stem cells.

Nat Cell Biol. 2017 May;19(5):542-549

Authors: Chen YW, Huang SX, de Carvalho ALRT, Ho SH, Islam MN, Volpi S, Notarangelo LD, Ciancanelli M, Casanova JL, Bhattacharya J, Liang AF, Palermo LM, Porotto M, Moscona A, Snoeck HW

Abstract
Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modelling, drug discovery and regenerative medicine. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation. Infection in vitro with respiratory syncytial virus, which causes small airway obstruction and bronchiolitis in infants, led to swelling, detachment and shedding of infected cells into the organoid lumens, similar to what has been observed in human lungs. Introduction of mutation in HPS1, which causes an early-onset form of intractable pulmonary fibrosis, led to accumulation of extracellular matrix and mesenchymal cells, suggesting the potential use of this model to recapitulate fibrotic lung disease in vitro. LBOs therefore recapitulate lung development and may provide a useful tool to model lung disease.

PMID: 28436965 [PubMed - indexed for MEDLINE]

Third-ventricle enterogenous cyst presentation mimicking a colloid cyst: uncommon presentation of a rare disease and literature review.

Acta Neurochir (Wien). 2017 Mar;159(3):465-468

Authors: Lavrador JP, Brogna C, Vergani F, Hasegawa H, Aizpurua M, Bhangoo R

Abstract
Enterogenous cysts (ECs) are endodermal lesions resulting from splitting anomalies in the neuroenteric canal. We report the case of a 64-year-old patient who presented with a sudden headache followed by collapse. Brain computed tomography revealed a hyperdense lesion in the anterior part of the third ventricle with obstructive hydrocephalus. A presumptive diagnosis of colloid cyst was made and he underwent a right transcortical approach for lesion resection. The histopathological examination revealed an EC. ECs are common lesions in the cervical-thoracic spine but rare in the supratentorial compartment with only two previously described cases occurring in the third ventricle.

PMID: 27981391 [PubMed - indexed for MEDLINE]

Proliferating subcutaneous nodules in a 12-year-old girl.

Clin Exp Dermatol. 2016 Jun;41(4):451-3

Authors: Gao J, Mann J, Abou-Alfa K, Duarte Williamson E, Calonje E

PMID: 26644195 [PubMed - indexed for MEDLINE]

[Deregulation of pre-messenger RNA splicing and rare diseases].

Med Sci (Paris). 2016 Dec;32(12):1111-1119

Authors: de la Grange P

Abstract
Most of protein-coding human genes are subjected to alternative pre-mRNA splicing. This mechanism is highly regulated to precisely modulate detection of specific splice sites. This regulation is under control of the spliceosome and several splicing factors are also required to modulate the alternative usage of splice sites. Splicing factors and spliceosome components recognize splicing signals and regulatory sequences of the pre-mRNAs. These splicing sequences make splicing susceptible to polymorphisms and mutations. Examples of associations between human rare diseases and defects in pre-messenger RNA splicing are accumulating. Although many alterations are caused by mutations in splicing sequence (i.e., cis acting mutations), recent studies described the disruptive impact of mutations within spliceosome components or splicing factors (i.e., trans acting mutations). Following growing of knowledge regarding splicing regulation, several approaches have been developed to compensate for the effect of deleterious mutations and to restore sufficient amounts of functional protein.

PMID: 28044975 [PubMed - indexed for MEDLINE]

Familial Kleine-Levin Syndrome: A Specific Entity?

Sleep. 2016 Aug 01;39(8):1535-42

Authors: Nguyen QT, Groos E, Leclair-Visonneau L, Monaca-Charley C, Rico T, Farber N, Mignot E, Arnulf I

Abstract
STUDY OBJECTIVES: Kleine-Levin syndrome (KLS) is a rare, mostly sporadic disorder, characterized by intermittent episodes of hypersomnia plus cognitive and behavior disorders. Although its cause is unknown, multiplex families have been described. We contrasted the clinical and biological features of familial versus sporadic KLS.
METHODS: Two samples of patients with KLS from the United States and France (n = 260) were studied using clinical interviews and human leukocyte antigen (HLA) genotyping. A multiplex family contained two or more first- or second-degree affected relatives (familial cases).
RESULTS: Twenty-one patients from 10 multiplex families (siblings: n = 12, including two pairs of monozygotic twins; parent-child: n = 4; cousins: n = 2; uncle-nephews: n = 3) and 239 patients with sporadic KLS were identified, yielding to 4% multiplex families and 8% familial cases. The simplex and multiplex families did not differ for autoimmune, neurological, and psychiatric disorders. Age, sex ratio, ethnicity, HLA typing, karyotyping, disease course, frequency, and duration of KLS episodes did not differ between groups. Episodes were less frequent in familial versus sporadic KLS (2.3 ± 1.8/y versus 3.8 ± 3.7/y, P = 0.004). Menses triggered more frequently KLS onset in the nine girls with familial KLS (relative risk, RR = 4.12, P = 0.03), but not subsequent episodes. Familial cases had less disinhibited speech (RR = 3.44, P = 0.049), less combined hypophagia/hyperphagia (RR = 4.38, P = 0.006), more abrupt termination of episodes (RR = 1.45, P = 0.04) and less postepisode insomnia (RR = 2.16, P = 0.008). There was similar HLA DQB1 distribution in familial versus sporadic cases and no abnormal karyotypes.
CONCLUSION: Familial KLS is mostly present in the same generation, and is clinically similar to but slightly less severe than sporadic KLS.

PMID: 27253765 [PubMed - indexed for MEDLINE]

[Frosted branch angiitis : Clinical findings and Spectralis OCT follow-up].

Ophthalmologe. 2016 Aug;113(8):699-703

Authors: Bergua A, Galiano M, Hohberger B, Rudolph M

Abstract
Frosted branch angiitis is a special form of retinal vasculitis, which has only rarely been reported in the literature. Although the majority of cases of frosted branch angiitis are idiopathic, a systematic clinical work-up should be done in order to exclude other causes, such as infectious and autoimmune diseases. The aim of this study was to correlate the clinical findings with the images obtained during follow-up by spectral domain optical coherence tomography (OCT).

PMID: 26612759 [PubMed - indexed for MEDLINE]

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/09/07

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Haematopoietic stem and progenitor cells from human pluripotent stem cells.

Nature. 2017 05 25;545(7655):432-438

Authors: Sugimura R, Jha DK, Han A, Soria-Valles C, da Rocha EL, Lu YF, Goettel JA, Serrao E, Rowe RG, Malleshaiah M, Wong I, Sousa P, Zhu TN, Ditadi A, Keller G, Engelman AN, Snapper SB, Doulatov S, Daley GQ

Abstract
A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders.

PMID: 28514439 [PubMed - indexed for MEDLINE]

Potential Reuse of Oncology Drugs in the Treatment of Rare Diseases.

Trends Pharmacol Sci. 2016 Oct;37(10):843-57

Authors: Liu Z, Fang H, Slikker W, Tong W

Abstract
Cancer research has made remarkable progress with the help of advancing genomics techniques, resulting in more precise clinical application and many new anticancer drugs on the market. By contrast, very few treatment options are available for rare diseases that are often progressive, severe, and life-threatening. In this opinion we elaborate on the possible association between cancers and rare diseases across three different levels including clinical observation, crosstalk between germline mutation and somatic mutation, and shared biological pathways. Consequently, by utilizing systematic drug-repositioning approaches, and taking safety issues into consideration, we suggest that oncology drugs have great potential for reuse in the treatment of rare diseases.

PMID: 27461952 [PubMed - indexed for MEDLINE]

Is Adrenal Insufficiency a Rare Disease?

Front Horm Res. 2016;46:106-14

Authors: Dahlqvist P, Isaksson M, Bensing S

Abstract
Adrenal insufficiency (AI) is a potentially life-threatening condition and it is of utmost importance to identify and adequately manage affected individuals. Diagnosis is often delayed, probably partly because diseases of the adrenal or pituitary region that cause primary AI (PAI) or central AI are relatively rare conditions. However, iatrogenic AI, i.e. the physiological downregulation of the hypothalamic-pituitary-adrenal axis and adrenal atrophy caused by glucocorticoid treatment for different inflammatory conditions is likely to be considerably more common. The type of glucocorticoid, dose and duration of treatment are factors to consider when trying to predict the risk of developing symptoms of AI. However, the considerable individual variation in the sensitivity for developing iatrogenic AI impedes prediction. In industrialized countries, autoimmune adrenalitis accounts for the majority of cases of PAI. Among children, genetic conditions - in particular congenital adrenal hyperplasia - need to be considered. Important risk groups for central AI are patients with tumours in the hypothalamic-pituitary region, moderate-to-severe traumatic head injury and patients who receive cranial radiotherapy or cytotoxic T-lymphocyte antigen 4 blockade treatment. Structured endocrine follow-up is essential in these groups. Health workers need to be attentive to these potentially fatal conditions and at-risk populations should be carefully informed about symptoms and signs of AI.

PMID: 27210825 [PubMed - indexed for MEDLINE]

9 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/09/02

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

9 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/09/02

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Midterm Outcomes of 12 Renal Transplant Recipients Treated With Eculizumab to Prevent Atypical Hemolytic Syndrome Recurrence.

Transplantation. 2017 Aug 25;:

Authors: Levi C, Frémeaux-Bacchi V, Zuber J, Rabant M, Devriese M, Snanoudj R, Scemla A, Amrouche L, Mejean A, Legendre C, Sberro-Soussan R

Abstract
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is an orphan disease with a high rate of recurrence after kidney transplantation. However, reports of successful prevention of posttransplant aHUS recurrence with eculizumab emerged a few years ago. To further delineate its optimal use, we describe the largest series of kidney transplant recipients treated with prophylactic eculizumab.
METHODS: Twelve renal transplant recipients with aHUS-related end stage renal disease received eculizumab: 10 from day 0 and 2 at the time of recurrence (days 6 and 25). Clinical and histological features, complement assessment and free eculizumab measurements were analyzed. The median follow-up was 24.6 months.
RESULTS: 5 patients had failed at least 1 previous renal transplant from aHUS. A genetic mutation was identified in 9 patients, anti-H antibodies were found in 2. No patient demonstrated biological recurrence of thrombotic microangiopathy (TMA) under treatment. Three antibody-mediated rejections (ABMRs) occurred without detectable C5 residual activity. ABMR was associated with subclinical TMA in 2 patients. One patient lost his graft after several complications, including ABMR. One patient experienced post-transplant C3 glomerulonephritis. The last median serum creatinine was 128.2 ± 40.8 μmol/l.
CONCLUSIONS: These data confirm that eculizumab is highly effective in preventing posttransplantation aHUS recurrence, yet may not fully block ABMR pathogenesis.

PMID: 28858176 [PubMed - as supplied by publisher]

Uromodulin: from physiology to rare and complex kidney disorders.

Nat Rev Nephrol. 2017 Sep;13(9):525-544

Authors: Devuyst O, Olinger E, Rampoldi L

Abstract
Uromodulin (also known as Tamm-Horsfall protein) is exclusively produced in the kidney and is the most abundant protein in normal urine. The function of uromodulin remains elusive, but the available data suggest that this protein might regulate salt transport, protect against urinary tract infection and kidney stones, and have roles in kidney injury and innate immunity. Interest in uromodulin was boosted by genetic studies that reported involvement of the UMOD gene, which encodes uromodulin, in a spectrum of rare and common kidney diseases. Rare mutations in UMOD cause autosomal dominant tubulointerstitial kidney disease (ADTKD), which leads to chronic kidney disease (CKD). Moreover, genome-wide association studies have identified common variants in UMOD that are strongly associated with risk of CKD and also with hypertension and kidney stones in the general population. These findings have opened up a new field of kidney research. In this Review we summarize biochemical, physiological, genetic and pathological insights into the roles of uromodulin; the mechanisms by which UMOD mutations cause ADTKD, and the association of common UMOD variants with complex disorders.

PMID: 28781372 [PubMed - indexed for MEDLINE]

Brexit and rare diseases: big risk, bigger opportunity?

Curr Med Res Opin. 2017 Apr;33(4):783-784

Authors: Hyry HI, Cox TM, Roos JC

Abstract
The UK's planned exit from the EU will leave its national health sector in a very dangerous position. It will also have profound consequences for domestic UK law. The impact may be particularly drastic for patients for whom EU law protects the right to treatment. At a particular risk are patients with rare, 'orphan', diseases whose treatments are uniquely enabled at the EU level. We examine the potential effects of Brexit on the orphan sector and identify an opportunity to solve long-standing and intensifying difficulties, especially the pricing of orphan drugs.

PMID: 28100081 [PubMed - indexed for MEDLINE]

8 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/08/31

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Endpoints in the design of clinical trials for primary sclerosing cholangitis.

Biochim Biophys Acta. 2017 Aug 25;:

Authors: Ponsioen CY

Abstract
Primary sclerosing cholangitis is an enigmatic disease affecting the bile ducts, eventually leading to liver failure necessitating liver transplantation in many cases. There is currently no therapy that has proven to halt disease progression. One of the reasons for this is the lack of proper endpoints to measure the effect of medical intervention on the course of the disease. Relevant clinical endpoints such as death or liver tranplsantation occur too infrequently in this orphan disease to be used as endpoints in phase 2 or 3 trials. It is therefore of utmost importance to identify appropriate surrogate endpoints that are reasonably likely to measure true clinical benefit. This artile will discuss a number of surrogate endpoints that are likely candidates to serve this role. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

PMID: 28847513 [PubMed - as supplied by publisher]

Precision medicine in rare disease: Mechanisms of disparate effects of N-carbamyl-l-glutamate on mutant CPS1 enzymes.

Mol Genet Metab. 2017 Mar;120(3):198-206

Authors: Shi D, Zhao G, Ah Mew N, Tuchman M

Abstract
This study documents the disparate therapeutic effect of N-carbamyl-l-glutamate (NCG) in the activation of two different disease-causing mutants of carbamyl phosphate synthetase 1 (CPS1). We investigated the effects of NCG on purified recombinant wild-type (WT) mouse CPS1 and its human corresponding E1034G (increased ureagenesis on NCG) and M792I (decreased ureagenesis on NCG) mutants. NCG activates WT CPS1 sub-optimally compared to NAG. Similar to NAG, NCG, in combination with MgATP, stabilizes the enzyme, but competes with NAG binding to the enzyme. NCG supplementation activates available E1034G mutant CPS1 molecules not bound to NAG enhancing ureagenesis. Conversely, NCG competes with NAG binding to the scarce M792I mutant enzyme further decreasing residual ureagenesis. These results correlate with the respective patient's response to NCG. Particular caution should be taken in the administration of NCG to patients with hyperammonemia before their molecular bases of their urea cycle disorders is known.

PMID: 28007335 [PubMed - indexed for MEDLINE]