16 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 2020/04/28

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.

7 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 2020/04/25

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.

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 2020/04/24

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.

Small-Molecule PAPD5 Inhibitors Restore Telomerase Activity in Patient Stem Cells.

Cell Stem Cell. 2020 Apr 17;:

Authors: Nagpal N, Wang J, Zeng J, Lo E, Moon DH, Luk K, Braun RO, Burroughs LM, Keel SB, Reilly C, Lindsley RC, Wolfe SA, Tai AK, Cahan P, Bauer DE, Fong YW, Agarwal S

Abstract
Genetic lesions that reduce telomerase activity inhibit stem cell replication and cause a range of incurable diseases, including dyskeratosis congenita (DC) and pulmonary fibrosis (PF). Modalities to restore telomerase in stem cells throughout the body remain unclear. Here, we describe small-molecule PAPD5 inhibitors that demonstrate telomere restoration in vitro, in stem cell models, and in vivo. PAPD5 is a non-canonical polymerase that oligoadenylates and destabilizes telomerase RNA component (TERC). We identified BCH001, a specific PAPD5 inhibitor that restored telomerase activity and telomere length in DC patient induced pluripotent stem cells. When human blood stem cells engineered to carry DC-causing PARN mutations were xenotransplanted into immunodeficient mice, oral treatment with a repurposed PAPD5 inhibitor, the dihydroquinolizinone RG7834, rescued TERC 3' end maturation and telomere length. These findings pave the way for developing systemic telomere therapeutics to counteract stem cell exhaustion in DC, PF, and possibly other aging-related diseases.

PMID: 32320679 [PubMed - as supplied by publisher]

Drug Development for Rare Paediatric Epilepsies: Current State and Future Directions.

Drugs. 2019 Dec;79(18):1917-1935

Authors: Auvin S, Avbersek A, Bast T, Chiron C, Guerrini R, Kaminski RM, Lagae L, Muglia P, Cross JH

Abstract
Rare diseases provide a challenge in the evaluation of new therapies. However, orphan drug development is of increasing interest because of the legislation enabling facilitated support by regulatory agencies through scientific advice, and the protection of the molecules with orphan designation. In the landscape of the rare epilepsies, very few syndromes, namely Dravet syndrome, Lennox-Gastaut syndrome and West syndrome, have been subject to orphan drug development. Despite orphan designations for rare epilepsies having dramatically increased in the past 10 years, the number of approved drugs remains limited and restricted to a handful of epilepsy syndromes. In this paper, we describe the current state of orphan drug development for rare epilepsies. We identified a large number of compounds currently under investigation, but mostly in the same rare epilepsy syndromes as in the past. A rationale for further development in rare epilepsies could be based on the match between the drug mechanisms of action and the knowledge of the causative gene mutation or by evidence from animal models. In case of the absence of strong pathophysiological hypotheses, exploratory/basket clinical studies could be helpful to identify a subpopulation that may benefit from the new drug. We provide some suggestions for future improvements in orphan drug development such as promoting paediatric drug investigations, better evaluation of the incidence and the prevalence, together with the natural history data, and the development of new primary outcomes.

PMID: 31734883 [PubMed - indexed for MEDLINE]

Pediatric Pulmonology Year in Review 2018: Rare lung disease, neuromuscular disease, and diagnostic testing.

Pediatr Pulmonol. 2019 11;54(11):1655-1662

Authors: Gower WA, Birnkrant DJ, Black JB, Noah TL

Abstract
Pediatric Pulmonology publishes original research, case reports, and review articles on topics related to a wide range of children's respiratory disorders. In this article, we highlight the past year's publications in the topic areas of rare lung diseases, respiratory complications of neuromuscular disorders, and diagnostic testing, as well as selected literature in these areas from other journals.

PMID: 31402599 [PubMed - indexed for MEDLINE]

Beckwith-Wiedemann syndrome in diverse populations.

Am J Med Genet A. 2019 04;179(4):525-533

Authors: Duffy KA, Sajorda BJ, Yu AC, Hathaway ER, Grand KL, Deardorff MA, Kalish JM

Abstract
Beckwith-Wiedemann syndrome (BWS) is the most common epigenetic overgrowth disorder and presents with patients affected by a variety of clinical features. Although genotype-phenotype correlations have been demonstrated in BWS and although BWS has been reported to occur equally among racial and ethnic backgrounds, no study to date has evaluated the frequency of findings in different backgrounds. In this study, we evaluated the incidence of clinical features and molecular diagnoses among patients with BWS in Caucasian, Mixed, and non-Caucasian groups. These results suggest that clinical features and molecular diagnoses differ between race/ethnicity groups and raise the possibility of race and ethnicity effects on genotype-phenotype correlations in BWS.

PMID: 30719840 [PubMed - indexed for MEDLINE]

QJM providing a platform for enhancing our knowledge for rare diseases.

QJM. 2018 Aug 01;111(8):513-514

Authors: Donnelly SC

PMID: 31986215 [PubMed - indexed for MEDLINE]

A patient-researcher partnership for rare cancer research.

Nat Med. 2020 02;26(2):164-165

Authors: Staniszewka S

PMID: 32042195 [PubMed - indexed for MEDLINE]

The Angiosarcoma Project: enabling genomic and clinical discoveries in a rare cancer through patient-partnered research.

Nat Med. 2020 02;26(2):181-187

Authors: Painter CA, Jain E, Tomson BN, Dunphy M, Stoddard RE, Thomas BS, Damon AL, Shah S, Kim D, Gómez Tejeda Zañudo J, Hornick JL, Chen YL, Merriam P, Raut CP, Demetri GD, Van Tine BA, Lander ES, Golub TR, Wagle N

Abstract
Despite rare cancers accounting for 25% of adult tumors1, they are difficult to study due to the low disease incidence and geographically dispersed patient populations, which has resulted in significant unmet clinical needs for patients with rare cancers. We assessed whether a patient-partnered research approach using online engagement can overcome these challenges, focusing on angiosarcoma, a sarcoma with an annual incidence of 300 cases in the United States. Here we describe the development of the Angiosarcoma Project (ASCproject), an initiative enabling US and Canadian patients to remotely share their clinical information and biospecimens for research. The project generates and publicly releases clinically annotated genomic data on tumor and germline specimens on an ongoing basis. Over 18 months, 338 patients registered for the ASCproject, which comprises a large proportion of all patients with angiosarcoma. Whole-exome sequencing (WES) of 47 tumors revealed recurrently mutated genes that included KDR, TP53, and PIK3CA. PIK3CA-activating mutations were observed predominantly in primary breast angiosarcoma, which suggested a therapeutic rationale. Angiosarcoma of the head, neck, face and scalp (HNFS) was associated with a high tumor mutation burden (TMB) and a dominant ultraviolet damage mutational signature, which suggested that for the subset of patients with angiosarcoma of HNFS, ultraviolet damage may be a causative factor and that immune checkpoint inhibition may be beneficial. Medical record review revealed that two patients with HNFS angiosarcoma had received off-label therapeutic use of antibody to the programmed death-1 protein (anti-PD-1) and had experienced exceptional responses, which highlights immune checkpoint inhibition as a therapeutic avenue for HNFS angiosarcoma. This patient-partnered approach has catalyzed an opportunity to discover the etiology and potential therapies for patients with angiosarcoma. Collectively, this proof-of-concept study demonstrates that empowering patients to directly participate in research can overcome barriers in rare diseases and can enable discoveries.

PMID: 32042194 [PubMed - indexed for MEDLINE]

The global prevalence and genetic spectrum of lysosomal acid lipase deficiency: A rare condition that mimics NAFLD.

J Hepatol. 2019 01;70(1):142-150

Authors: Carter A, Brackley SM, Gao J, Mann JP

Abstract
BACKGROUND & AIMS: Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive condition that may present in a mild form (cholesteryl ester storage disease [CESD]), which mimics non-alcoholic fatty liver disease (NAFLD). It has been suggested that CESD may affect 1 in 40,000 and is under-diagnosed in NAFLD clinics. Therefore, we aimed to estimate the prevalence of LAL-D using analysis of genetic variation in LIPA.
METHODS: MEDLINE and EMBASE were systematically searched for previously reported disease variants and prevalence estimates. Previous prevalence estimates were meta-analysed. Disease variants in LIPA were annotated with allele frequencies from gnomAD and combined with unreported major functional variants found in humans. Pooled ethnicity-specific prevalences for LAL-D and CESD were calculated using the Hardy-Weinberg equation.
RESULTS: Meta-analysis of existing genetic studies estimated the prevalence of LAL-D as 1 per 160,000 (95% CI 1 per 65,025-761,652) using the allele frequency of c.894G>A in LIPA. A total of 98 previously reported disease variants in LIPA were identified, of which 32/98 were present in gnomAD, giving a prevalence of 1 per 307,482 (95% CI 257,672-366,865). Wolman disease was associated with more loss-of-function variants than CESD. When this was combined with 22 previously unreported major functional variants in LIPA identified in humans, the pooled prevalence of LAL-D was 1 per 177,452 (95% CI 149,467-210,683) with a carrier frequency of 1 per 421. The prevalence is lowest in those of East Asian, South Asian, and Finnish ancestry.
CONCLUSION: Using 120 disease variants in LIPA, these data can reassure clinicians that LAL-D is an ultra-rare disorder. Given the therapeutic capability of sebelipase alpha, investigation for LAL-D might be included in second-line metabolic screening in NAFLD.
LAY SUMMARY: Lysosomal Acid Lipase Deficiency (LAL-D) is a rare genetic condition that can cause severe liver disease, but it is difficult to diagnose and sometimes can look like simple fatty liver. It was not clear how common LAL-D was and whether many cases were being missed. To study this, we searched for all genetic mutations that could cause LAL-D, calculated how common those mutations were, and added them up. This let us estimate that LAL-D affects roughly 1 in 175,000 people. We conclude that LAL-D is a very rare condition, but it is treatable so may be included in a 'second-line' of tests for causes of fatty liver.

PMID: 30315827 [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 2020/04/21

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.

The Canadian Rare Diseases Models and Mechanisms (RDMM) Network: Connecting Understudied Genes to Model Organisms.

Am J Hum Genet. 2020 02 06;106(2):143-152

Authors: Boycott KM, Campeau PM, Howley HE, Pavlidis P, Rogic S, Oriel C, Berman JN, Hamilton RM, Hicks GG, Lipshitz HD, Masson JY, Shoubridge EA, Junker A, Leroux MR, McMaster CR, Michaud JL, Turvey SE, Dyment D, Innes AM, van Karnebeek CD, Lehman A, Cohn RD, MacDonald IM, Rachubinski RA, Frosk P, Vandersteen A, Wozniak RW, Pena IA, Wen XY, Lacaze-Masmonteil T, Rankin C, Hieter P

Abstract
Advances in genomics have transformed our ability to identify the genetic causes of rare diseases (RDs), yet we have a limited understanding of the mechanistic roles of most genes in health and disease. When a novel RD gene is first discovered, there is minimal insight into its biological function, the pathogenic mechanisms of disease-causing variants, and how therapy might be approached. To address this gap, the Canadian Rare Diseases Models and Mechanisms (RDMM) Network was established to connect clinicians discovering new disease genes with Canadian scientists able to study equivalent genes and pathways in model organisms (MOs). The Network is built around a registry of more than 500 Canadian MO scientists, representing expertise for over 7,500 human genes. RDMM uses a committee process to identify and evaluate clinician-MO scientist collaborations and approve 25,000 Canadian dollars in catalyst funding. To date, we have made 85 clinician-MO scientist connections and funded 105 projects. These collaborations help confirm variant pathogenicity and unravel the molecular mechanisms of RD, and also test novel therapies and lead to long-term collaborations. To expand the impact and reach of this model, we made the RDMM Registry open-source, portable, and customizable, and we freely share our committee structures and processes. We are currently working with emerging networks in Europe, Australia, and Japan to link international RDMM networks and registries and enable matches across borders. We will continue to create meaningful collaborations, generate knowledge, and advance RD research locally and globally for the benefit of patients and families living with RD.

PMID: 32032513 [PubMed - indexed for MEDLINE]

Room for improvement in clinical trials for rare diseases.

Nat Rev Rheumatol. 2020 03;16(3):131-132

Authors: Musters A, Tas SW

PMID: 31996788 [PubMed - indexed for MEDLINE]

Harmonizing care for rare diseases: How we developed the mitochondrial care network in the United States.

Mol Genet Metab. 2019 06;127(2):122-127

Authors: Karaa A, Goldstein A, Balcells C, Mann K, Stanley L, Yeske PE, Parikh S

Abstract
The mitochondrial medicine society (MMS) has previously highlighted the clinical landscape and physician practice patterns of mitochondrial medicine in the US and attempted to develop consensus criteria for diagnosis and management to improve patient coordinated care. Most recently, and in collaboration with US-based patient advocacy groups, we developed a clinical care network to formally unify US-based clinicians who provide medical care to individuals with mitochondrial disease; to define, design and implement best practices in mitochondrial medicine building on the current consensus guidelines and to improve patients' clinical outcomes. Here we review the steps taken in collaboration with several stakeholders to develop goals and expectations for a mitochondrial care network (MCN), criteria for MCN site selection and formal launch of the network.

PMID: 31138493 [PubMed - indexed for MEDLINE]

Health information behaviour of rare disease patients: seeking, finding and sharing health information.

Health Info Libr J. 2019 Dec;36(4):341-356

Authors: Stanarević Katavić S

Abstract
BACKGROUND: Rare disease patients find independent health information seeking necessary due to the general lack of knowledge on rare diseases and inadequate information provision by health care professionals.
OBJECTIVE: The aim of this study is to describe distinctive aspects of health information behaviour of rare disease patients and specific challenges they face when seeking health information.
METHODS: A qualitative research approach was employed including semi-structured interviews that were analysed using thematic analysis. Fifteen respondents suffering from three different rare diseases participated in the study.
RESULTS: Health information behaviour of rare disease patients is characterised by independent and continuous health information seeking and sharing. Connecting with other patients and getting realistic insight into the condition after diagnosis, advice for everyday life, comfort and hope and confirmation that their symptoms are 'normal' are of particular importance. Lack of specific advice for daily life, inaccessible new knowledge, lack of information about drugs and encountering severe health information are common challenges patients face due to insufficient support from health care professionals.
CONCLUSION: Health information seeking and sharing are important aspects of rare disease patients' everyday life. Challenges they face could be overcome in cooperation with patient support groups, health care professionals and health information professionals.

PMID: 31099979 [PubMed - indexed for MEDLINE]

Spontaneous coronary artery dissection: no longer a rare disease.

Eur Heart J. 2019 04 14;40(15):1198-1201

Authors: Adlam D, García-Guimaraes M, Maas AHEM

PMID: 30844061 [PubMed - indexed for MEDLINE]

Acute spontaneous suppurative thyroiditis caused by Eikenella corrodens presented with thyrotoxicosis.

Einstein (Sao Paulo). 2020;18:eRC5273

Authors: Akhanlı P, Bayır Ö, Bayram SM, Hepşen S, Badirshaev M, Çakal E, Saylam G, Korkmaz MH

Abstract
Acute suppurative thyroiditis is a very rare and life-threatening endocrine emergency. Thyrotoxicosis is a rare condition accompanying acute suppurative thyroiditis. While the majority of the cases in the literature are caused by different reasons, spontaneous development is very rare. We present a patient with acute suppurative thyroiditis who presented to our clinic with thyrotoxic findings, and we compared the case to the literature. A 31-year-old male patient was admitted to our clinic with a complaint of progressive neck pain, swelling and redness on midline neck, fever, and palpitations. On physical examination, swelling, redness and tenderness were detected on the neck region that was consistent with the thyroid location. He presented with tremor on the hands, tachycardia and agitation. Thyroid function tests were compatible with thyrotoxicosis, but there were findings supporting the presence of infection in biochemistry tests. On his radiological evaluations, a heterogeneous lesion divided with small septs was observed, with consolidation areas in the left thyroid lobe. In fine needle aspiration biopsy, 2mL of purulent fluid could be aspirated due to the presence of small, separated consolidation areas. He initiated on antibiotic therapy, propranolol, steroid and symptomatic treatment. Eikenella corrodens was detected on the culture antibiogram. Antibiotic therapy was continued for 14 days due to less symptoms and better biochemical values. After treatment, the patient had normal thyroid function, had relief of fever and redness of the neck, and was followed-up. It should be kept in mind that acute suppurative thyroiditis may develop spontaneously with the findings of thyrotoxicosis, with no risk factors.

PMID: 32215470 [PubMed - indexed for MEDLINE]

Surgical Technique for Nasal Cleft Repair.

Ann Plast Surg. 2019 03;82(3):289-291

Authors: Chapchay K, Zaga J, Billig A, Adler N, Margulis A

Abstract
BACKGROUND: Congenital nasal cleft is a very rare yet challenging deformity to reconstruct. Atypical craniofacial clefts that involve the nasal ala are designated as number 1 and number 2 under the Tessier classification system. These clefts typically present as notches in the medial one-third of either nasal ala and may be accompanied by a malpositioned cartilaginous framework. Nasal clefts are smaller and far less common than familiar clefts of the lip and palate, but they pose equally challenging reconstructive planning.
METHODS: Our described technique relies on usage of existing nasal tissue near the cleft. Local tissue rearrangement using a laterally based rotational alar flap, a medially based triangular flap, and a nasal wall advancement flap restores normal anatomy and provides an aesthetically pleasing result.
RESULTS: Five children with isolated nasal cleft were treated by the senior author (A.M.) between 2010 and 2017. All patients presented with clefts of the soft tissue with no underlying cartilaginous involvement. There were no postoperative complications. Excellent aesthetic outcome was achieved in all patients.
CONCLUSION: Isolated nasal cleft can be properly corrected with the described procedure in a single stage and with optimal result.

PMID: 30562204 [PubMed - indexed for MEDLINE]

Rare bleeding disorders and advances in gene therapy.

Blood Coagul Fibrinolysis. 2019 Dec;30(8):371-378

Authors: Liu T, Yang Z

Abstract
: Rare bleeding disorders usually begin in childhood and manifest as varying degrees of bleeding, which can be life-threatening in severe cases. With the development of gene editing technology, it is expected that hereditary coagulation factor disorders will someday be fundamentally cured by gene therapy. On account of their rarity, comprehension of these diseases is essential for the application of new treatment strategies. We have compiled the features of some newly discovered mutations of prothrombin, factor VII, and factor X in recent years. In addition, this review introduces the advances and obstacles in gene therapy.

PMID: 31738733 [PubMed - indexed for MEDLINE]