Expanding the Phenotypic and Genotypic Landscape of Autoimmune Polyendocrine Syndrome Type 1.

J Clin Endocrinol Metab. 2017 Sep 01;102(9):3546-3556

Authors: Orlova EM, Sozaeva LS, Kareva MA, Oftedal BE, Wolff ASB, Breivik L, Zakharova EY, Ivanova ON, Kämpe O, Dedov II, Knappskog PM, Peterkova VA, Husebye ES

Abstract
Context: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene and characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. Comprehensive characterizations of large patient cohorts are rare.
Objective: To perform an extensive clinical, immunological, and genetic characterization of a large nationwide Russian APS-1 cohort.
Subjects and Methods: Clinical components were mapped by systematic investigations, sera were screened for autoantibodies associated with APS-1, and AIRE mutations were characterized by Sanger sequencing.
Results: We identified 112 patients with APS-1, which is, to the best of our knowledge, the largest cohort described to date. Careful phenotyping revealed several additional and uncommon phenotypes such as cerebellar ataxia with pseudotumor, ptosis, and retinitis pigmentosa. Neutralizing autoantibodies to interferon-ω were found in all patients except for one. The major Finnish mutation c.769C>T (p.R257*) was the most frequent and was present in 72% of the alleles. Altogether, 19 different mutations were found, of which 9 were unknown: c.38T>C (p.L13P), c.173C>T (p.A58V), c.280C>T (p.Q94*), c.554C>G (p.S185*), c.661A>T (p.K221*), c.821del (p.Gly274Afs*104), c.1195G>C (p.A399P), c.1302C>A (p.C434*), and c.1497del (p.A500Pfs*21).
Conclusions: The spectrum of phenotypes and AIRE mutation in APS-1 has been expanded. The Finnish major mutation is the most common mutation in Russia and is almost as common as in Finland. Assay of interferon antibodies is a robust screening tool for APS-1.

PMID: 28911151 [PubMed - indexed for MEDLINE]

AcroangiodermatitisA Presentation of Two Cases of Nonhealing Ulcerations in the Lower Extremity.

J Am Podiatr Med Assoc. 2016 Sep 02;106(5):364-369

Authors: Hronek AL, Clark SN, Young G, Kinikini D, Wells J

Abstract
Acroangiodermatitis (AAD), also known as pseudo-Kaposi's sarcoma, is an uncommon benign angioproliferative condition most commonly seen in the lower extremities. This condition often presents as discolored patches that progress to painful ulcerations. The list of vascular conditions associated with this diagnosis is vast. Acroangiodermatitis presents similarly to more aggressive conditions such as Kaposi's sarcoma, making histopathologic examination helpful in its diagnosis. We present two cases of AAD in the setting of chronic venous insufficiency.

PMID: 27762609 [PubMed - indexed for MEDLINE]

Palatal Perforation as a Rare Complication of Nasal Septoplasty.

Aesthetic Plast Surg. 2016 Dec;40(6):850-853

Authors: Tilaveridis I, Kalaitsidou I, Kyrgidis A, Astreidis IS

Abstract
BACKGROUND: Nasal septoplasty is one of the most commonly performed surgical procedures by otolaryngologists or plastic surgeons and is generally performed to improve the quality of life. Although nasal surgeries are generally safe and effective procedures, various complications have been described in the literature.
METHODS: In this article, we present a rare case of fracture of a part of the hard palate resulting in palatal perforation after nasal septoplasty surgery early diagnosed and successfully treated.
RESULTS: Patient follow-up 1 year after oronasal closure revealed complete healing of the hard palate without the presence of fistula.
CONCLUSIONS: Palatal perforation during septoplasty is extremely rare and, even though it is not a life-threatening complication, has potentially annoying effects; according to its size, it can result in nasal speech, oral health problems, and nasal regurgitation of liquids and is sometimes related with reconstructive challenging problems.
LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the A5 online Instructions to Authors. www.springer.com/00266 .

PMID: 27631545 [PubMed - indexed for MEDLINE]

Primary mitral valve sarcoma: multimodality imaging and therapy.

Eur Heart J Cardiovasc Imaging. 2016 Oct;17(10):1137

Authors: Barber H, Menezes L, Dileo P, Lloyd G, Bhattacharyya S

PMID: 27369847 [PubMed - indexed for MEDLINE]

Kyasanur Forest Disease (KFD): Rare Disease of Zoonotic Origin.

J Nepal Health Res Counc. 2016 Sep;14(34):214-218

Authors: Muraleedharan M

Abstract
Kyasanur forest disease (KFD) is a rare tick borne zoonotic disease that causes acute febrile hemorrhagic illness in humans and monkeys especially in southern part of India. The disease is caused by highly pathogenic KFD virus (KFDV) which belongs to member of the genus Flavivirus and family Flaviviridae. The disease is transmitted to monkeys and humans by infective tick Haemaphysalisspinigera. Seasonal outbreaks are expected to occur during the months of January to June. The aim of this paper is to briefly summarize the epidemiology, mode of transmission of KFD virus, clinical findings, diagnosis, treatment, control and prevention of the disease..

PMID: 28327690 [PubMed - indexed for MEDLINE]

Rare and difficult to treat haematological diseases.

Lancet Haematol. 2015 Jan;2(1):e1

Authors:

PMID: 26687422 [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 2017/10/11

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 2017/10/11

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.

Systemic Manifestations in Pyridox(am)ine 5'-Phosphate Oxidase Deficiency.

Pediatr Neurol. 2017 Jun 03;:

Authors: Guerriero RM, Patel AA, Walsh B, Baumer FM, Shah AS, Peters JM, Rodan LH, Agrawal PB, Pearl PL, Takeoka M

Abstract
OBJECTIVE: Pyridoxine is converted to its biologically active form pyridoxal-5-phosphate (P5P) by the enzyme pyridox(am)ine 5'-phosphate oxidase and serves as a cofactor in nearly 200 reactions in the central nervous system. Pyridox(am)ine 5'-phosphate oxidase deficiency leads to P5P dependent epilepsy, typically a neonatal- or infantile-onset epileptic encephalopathy treatable with P5P or in some cases, pyridoxine. Following identification of retinopathy in a patient with pyridox(am)ine 5'-phosphate oxidase deficiency that was reversible with P5P therapy, we describe the systemic manifestations of pyridox(am)ine 5'-phosphate oxidase deficiency.
METHODS: A series of six patients with homozygous mutations of PNPO, the gene coding pyridox(am)ine 5'-phosphate oxidase, were evaluated in our center over the course of two years for phenotyping of neurological and systemic manifestations.
RESULTS: Five of six were born prematurely, three had anemia and failure to thrive, and two had elevated alkaline phosphatase. A movement disorder was observed in two children, and a reversible retinopathy was observed in the most severely affected infant. All patients had neonatal-onset epilepsy and were on a continuum of developmental delay to profound encephalopathy. Electroencephalographic features included background slowing and disorganization, absent sleep features, and multifocal and generalized epileptiform discharges. All the affected probands carried a homozygous PNPO mutation (c.674 G>T, c.686 G>A and c.352G>A).
CONCLUSION: In addition to the well-described epileptic encephalopathy, pyridox(am)ine 5'-phosphate oxidase deficiency causes a range of neurological and systemic manifestations. A movement disorder, developmental delay, and encephalopathy, as well as retinopathy, anemia, and failure to thrive add to the broadening clinical spectrum of P5P dependent epilepsy.

PMID: 28985901 [PubMed - as supplied by publisher]

Fateful imprints.

Science. 2017 Jan 13;355(6321):122-125

Authors: Couzin-Frankel J

PMID: 28082544 [PubMed - indexed for MEDLINE]

17 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 2017/10/05

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.

17 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 2017/10/05

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.

A systems-level analysis of drug-target-disease associations for drug repositioning.

Brief Funct Genomics. 2017 Aug 17;:

Authors: Rutherford KD, Mazandu GK, Mulder NJ

Abstract
Drug repositioning is the process of finding new therapeutic uses for existing, approved drugs-a process thathas value when considering the exorbitant costs of novel drug development. Several computational strategies exist as a way to predict these alternative applications. In this study, we used datasets on: (1) human biological drug targets and (2) disease-associated genes and, based on a direct functional interaction between them, searched for potential opportunities for drug repositioning. From the set of 1125 unique drug targets and their 88 490 interactions with disease-associated genes, 30 drug targets were analyzed and (3) discussed in detail for the purpose of this article. The current indications of the drugs thattarget them were validated through the interactions, and new opportunities for repositioning were predicted. Among the set of drugs for potential repositioning werebenzodiazepines for the treatment of autism spectrum disorders; nortriptyline for the treatment of melanoma, glioma and other cancers; and vitamin B6 in prevention of spontaneous abortions and cleft palate birth defects. Special emphasis was also placed on those new potential indications that pertained to orphan diseases-these are diseases whose rarity means that development of novel treatment is not financially viable. This computational drug repositioning approach uses existing information on drugs and drug targets, and insights into the genetic basis of disease, as a means to systematically generate the most probable new uses for the drugs on offer, and in this way harness their true therapeutic power.

PMID: 28968683 [PubMed - as supplied by publisher]

Four Cases of Pneumatosis Cystoides Intestinalis Complicated by Connective Tissue Diseases.

Intern Med. 2017;56(9):1101-1106

Authors: Suzuki E, Kanno T, Hazama M, Kobayashi H, Watanabe H, Ohira H

Abstract
Pneumatosis cystoides intestinalis (PCI) is a rare disease that involves the presence of gas in the intestinal wall. Connective tissue disease (CTD) is a major cause of secondary PCI. In addition to the nature of CTDs, the use of prednisolone and some immunosuppressants, and the presence of complicating diseases such as diabetes mellitus, constipation and pulmonary diseases are involved in the development of PCI. This report describes four cases of PCI with different CTDs (granulomatosis with polyangiitis, rheumatoid arthritis, dermatomyositis, and overlap syndrome) and discusses the background of each patient and common risk factors for the occurrence of PCI.

PMID: 28458320 [PubMed - indexed for MEDLINE]

Isolated Gastric Varices Refractory to Balloon-occluded Retrograde Transvenous Obliteration (BRTO) Successfully Treated by Shunt-occluded Endoscopic Injection Sclerotherapy (SO-EIS): A Case Report and Review of the Literature.

Intern Med. 2017;56(9):1041-1048

Authors: Hatanaka T, Kakizaki S, Suzuki Y, Ueno T, Shimada Y, Takizawa D, Katakai K, Sato K, Kusano M, Yamada M

Abstract
Balloon-occluded retrograde transvenous obliteration (BRTO) is widely used to treat isolated gastric varices (IGVs) in Japan. However, BRTO is difficult to perform for IGVs with many small collateral veins, and no secondary treatment has been established. We herein report a rare case of IGVs refractory to BRTO successfully treated by shunt-occluded endoscopic injection sclerotherapy (SO-EIS), which is a combination therapy of major shunt occlusion by a balloon catheter and endoscopic injection sclerotherapy. Since SO-EIS can be performed regardless of the IGVs' anatomical configuration, it may be a promising alternative treatment for IGVs refractory to BRTO.

PMID: 28458309 [PubMed - indexed for MEDLINE]

The Human Phenotype Ontology in 2017.

Nucleic Acids Res. 2017 Jan 04;45(D1):D865-D876

Authors: Köhler S, Vasilevsky NA, Engelstad M, Foster E, McMurry J, Aymé S, Baynam G, Bello SM, Boerkoel CF, Boycott KM, Brudno M, Buske OJ, Chinnery PF, Cipriani V, Connell LE, Dawkins HJ, DeMare LE, Devereau AD, de Vries BB, Firth HV, Freson K, Greene D, Hamosh A, Helbig I, Hum C, Jähn JA, James R, Krause R, F Laulederkind SJ, Lochmüller H, Lyon GJ, Ogishima S, Olry A, Ouwehand WH, Pontikos N, Rath A, Schaefer F, Scott RH, Segal M, Sergouniotis PI, Sever R, Smith CL, Straub V, Thompson R, Turner C, Turro E, Veltman MW, Vulliamy T, Yu J, von Ziegenweidt J, Zankl A, Züchner S, Zemojtel T, Jacobsen JO, Groza T, Smedley D, Mungall CJ, Haendel M, Robinson PN

Abstract
Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human Phenotype Ontology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

PMID: 27899602 [PubMed - indexed for MEDLINE]

Bilateral Internal Carotid Artery Segmental Agenesis: Embryology, Common Collateral Pathways, Clinical Presentation, and Clinical Importance of a Rare Condition.

World Neurosurg. 2016 Nov;95:620.e9-620.e15

Authors: Alexandre AM, Visconti E, Schiarelli C, Frassanito P, Pedicelli A

Abstract
BACKGROUND: Bilateral segmental agenesis of the internal carotid artery is a rare congenital anomaly. We present a case of bilateral internal carotid artery segmental agenesis in an asymptomatic 18-year-old man. Embryology, common collateral pathways, clinical presentation, and clinical importance of this condition are discussed. According to our review of the literature, this report is the first to describe bilateral internal carotid artery segmental agenesis in a patient studied with magnetic resonance imaging, computed tomography, Doppler ultrasonography, and digital subtraction angiography.
CASE DESCRIPTION: An 18-year-old man presented to our hospital complaining of occasional mild headaches. Neurologic examination was unremarkable. Imaging findings consisted of bilateral segmental agenesis of the internal carotid arteries.
CONCLUSION: Bilateral segmental agenesis of internal carotid artery may be completely asymptomatic and harmless, but associated conditions, such as cerebral aneurysms or abnormal collateral circulation, should alert clinicians to the possibilities of subarachnoid hemorrhage or cerebral ischemia.

PMID: 27535626 [PubMed - indexed for MEDLINE]

The Challenge of Guideline Development When Evidence Is Sparse.

Otolaryngol Head Neck Surg. 2017 Sep;157(3):383-384

Authors: Scharpf J

Abstract
Although best-practice standards for clinical guidelines have been released by the Institute of Medicine and Guidelines International Network, a great challenge remains for guideline development for patients afflicted with rare diseases. This article reviews the challenge of guideline development under these circumstances with an emphasis on strategies to overcome these challenges. Guideline development and use in practice have become integral components in the contemporary care of patients to optimize outcome results. The guidelines are developed through an objective, evidence-based process conducted by experts and stakeholders for a given disease process.

PMID: 28675089 [PubMed - indexed for MEDLINE]

Facial paralysis due to Ramsay Hunt syndrome - A rare condition.

Rev Assoc Med Bras (1992). 2017 Apr;63(4):301-302

Authors: Paiva ALC, Araujo JLV, Ferraz VR, Veiga JCE

Abstract
Ramsay Hunt syndrome (or herpes zoster oticus) is a rare complication of herpes zoster in which reactivation of latent varicella zoster virus infection in the geniculate ganglion occurs. Usually, there are auricular vesicles and symptoms and signs such otalgia and peripheral facial paralysis. In addition, rarely, a rash around the mouth can be seen. Immunodeficient patients are more susceptible to this condition. Diagnosis is essentially based on symptoms. We report the case of a diabetic female patient who sought the emergency department with a complaint of this rare entity.

PMID: 28614529 [PubMed - indexed for MEDLINE]

Simultaneous meningioma and brain metastasis from renal cell carcinoma - a rare presentation. Case report.

Sao Paulo Med J. 2017 May-Jun;135(3):296-301

Authors: Campos Paiva AL, Vitorino Araujo JL, Ferraz VR, Esteves Veiga JC

Abstract
CONTEXT:: Brain metastases are the most common tumors of the central nervous system. Because of their high frequency, they may be associated with rare situations. Among these are tumor-to-tumor metastasis and an even a rarer situation called simultaneous brain tumors, which are more related to primary tumors of the reproductive and endocrine systems.
CASE REPORT:: A 56-year-old male patient with a history of renal cell carcinoma (which had previously been resected) presented with a ventricular lesion (suggestive of metastatic origin) and simultaneous olfactory groove lesion (probably a meningioma). First, only the ventricular lesion was dealt with, but after a year, the meningothelial lesion increased and an occipital lesion appeared. Therefore, both of these were resected in a single operation. All the procedures were performed by the same neurosurgeon. The patient evolved without neurological deficits during the postoperative period. After these two interventions, the patient remained well and was referred for adjuvant treatment.
CONCLUSIONS:: This study provides the first description of an association between these two tumors. Brain metastases may be associated with several lesions, and rare presentations such as simultaneity with meningioma should alert neurosurgeons to provide the best oncological treatment.

PMID: 28562734 [PubMed - indexed for MEDLINE]