A case of concomitant intralobar bronchopulmonary sequestration and situs inversus totalis.

Clin Respir J. 2017 May;11(3):391-393

Authors: Barış MM, Gezer NS, Çelik AO, Kılınç O, Balcı P

Abstract
BACKGROUND AND AIMS: Situs inversus is a rare congenital abnormality involving partial or complete transposition of the thoracic or abdominal viscera. In situs inversus totalis, both the thoracic and abdominal viscera are transposed. The incidence of this condition is 0.01% to 0.02%. Bronchopulmonary sequestration (BPS) is a rare congenital abnormality of the respiratory tract with an incidence of 0.15% to 1.80%. Intralobar sequestration is uncommonly associated with congenital anomalies.
METHODS: A routine chest X-ray of a 41-year-old asymptomatic man showed dextrocardia, a left-sided liver, right-sided stomach, and left paracardiac opacity.
RESULTS: Computed tomography (CT) and CT pulmonary angiography revealed dextrocardia with situs inversus totalis and left paracardiac intralobar BPS in the lingular segment of the left upper lobe.
CONCLUSION: We present a rare case of combined situs inversus totalis and intralobar BPS with an atypical location and feeder artery.

PMID: 26177792 [PubMed - indexed for MEDLINE]

Sequential occurrence of combined pulmonary fibrosis and emphysema syndrome in a non-smoker female patient.

Clin Respir J. 2017 May;11(3):378-382

Authors: Gupta P, Dash D, Mittal R, Chhabra SK

Abstract
The combined pulmonary fibrosis and emphysema (CPFE) syndrome is a unique and an under-recognized disorder characterized by emphysema in the upper lobes and interstitial fibrosis in the lower lobes of the lung. It occurs predominantly in males and almost exclusively in smokers. This rare combination of a restrictive and an obstructive mechanical defect carries a poorer prognosis than either of the two components. We present a case of CPFE syndrome in a non-smoker female patient who developed lower lobe emphysema subsequent to development of interstitial fibrosis. The case was remarkable for the extreme rarity of several presenting features, namely, a lower lobe occurrence of emphysema subsequent to pre-existent interstitial fibrosis, female gender and absence of a history of smoking.

PMID: 26077104 [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 2018/03/01

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.

Prevalence of Rare Craniofacial Clefts.

J Craniofac Surg. 2017 Jul;28(5):e467-e470

Authors: Kalantar-Hormozi A, Abbaszadeh-Kasbi A, Goravanchi F, Davai NR

Abstract
BACKGROUND: Craniofacial clefts are extremely rare congenital malformations that have adverse functional, psychosocial, and aesthetic effects on patients' life. Although the exact incidence is unclear, it is estimated between 1.4 and 4.9 per 100,000 live births. Prevalence of the rare craniofacial clefts is imprecise due to the paucity of literature as well as their etiologies.
METHODS: All the patients with rare craniofacial clefts during 10 years in a plastic surgery tertiary referral hospital were included, and Tessier craniofacial clefting classification was used for classifying the clefts.
RESULTS: Of 964 patients with craniofacial clefts, 80 (8.29%) patients were identified with rare craniofacial clefts. There were 39 (48.7%) males and 41 (51.3%) females. Family history was determined positive in 30 (37.5%) patients. Tessier number 0 (58.7%) was the most common cleft in the authors' study. Tessier numbers 8, 13, and 30 were the rarest clefts. There was no patient with Clefts numbers 5, 6, or 9. Maternal smoking during pregnancy was observed in 1 (1.3%) of the women and 3 of the women had used drugs, 1 of them used the dexamethasone tablets and 2 of them could not remember name of the used drug.
CONCLUSIONS: Tessier number 0 was the most common cleft and Tessier numbers 8, 13, and 30 were the rarest types. The precise etiology of rare craniofacial clefts remained undetermined in this study. Women should be educated about the risk factors and subsequent ways of preventing from these risk factors.

PMID: 28678141 [PubMed - indexed for MEDLINE]

Physicochemical Properties of Bosentan and Selected PDE-5 Inhibitors in the Design of Drugs for Rare Diseases.

AAPS PharmSciTech. 2017 May;18(4):1318-1331

Authors: Krupa A, Majda D, Mozgawa W, Szlęk J, Jachowicz R

Abstract
The study provides the physicochemical characteristic of bosentan (BOS) in comparison to tadalafil (TA) and sildenafil citrate (SIL). Despite some reports dealing with thermal characteristic of SIL and TA, physicochemical properties of BOS have not been investigated so far. Recent clinical reports have indicated that the combination of bosentan and PDE-5 inhibitor can improve the effectiveness of pharmacotherapy of pulmonary arterial hypertension (PAH). However, in order to design personalized medicines for therapy of chronic rare diseases, detailed information on the thermal behaviour and solubility of each drug is indispensable. Thus, XRD, DSC and TGA-QMS analyses were applied to compare the properties of the drugs, their thermal stability as well as to identify the products of thermal degradation. The dehydration of BOS started at 70°C and was followed by the chemical degradation with the onset at 290°C. The highest thermal stability was stated for TA, which decomposed at ca. 320°C, whereas the lowest onset of the thermal decomposition process was stated for SIL, i.e. 190°C. The products of the drug decomposition were identified. FT-FIR was applied to study intra- and intermolecular interactions between the drug molecules. FT-MIR and Raman spectroscopy were used to examine the chemical structure of the drugs. Chemoinformatic tools were used to predict the polar surface area, pKa, or logP of the drugs. Their results were in line with solubility and dissolution studies.

PMID: 27495162 [PubMed - indexed for MEDLINE]

Communication strategies employed by rare disease patient organizations in Spain.

Cien Saude Colet. 2016 Aug;21(8):2423-36

Authors: Castillo-Esparcia A, López-Villafranca P

Abstract
The current study focuses on communication strategies employed by rare disease patient organizations. The aims of these organizations are: educate and inform the public about rare diseases, raise awareness of the problems related to rare diseases, and achieve social legitimacy in order give visibility to their demands. We analyzed the portrayal of rare disease and patient organizations by Spain's major media organizations in terms of circulation and viewership - the press (El País, El Mundo, La Vanguardia,ABC and El Periódico), radio (CadenaSer, Onda Cero, Cope and RNE), and television (Telecinco, Antena 3, La 1, La Sexta, Cuatro) -between 2012 and 2014.We then carried out a descriptive analysis of communication activities performed via the World Wide Web and social networks by 143 national organizations. Finally, we conducted a telephone questionnaire of a representative sample of 90 organizations in order to explore the association between media presence and funding and public image. The triangulation of quantitative and qualitative methods allowed us to meet the study's objectives. Increased visibility of the organizations afforded by an increase in the coverage of the topic by the medialed to an increase in membership - but not in donations - and increased awareness of these diseases.

PMID: 27557016 [PubMed - indexed for MEDLINE]

HPCA-related dystonia: Too rare to be found?

Mov Disord. 2016 07;31(7):1071

Authors: Dobričić V, Kresojević N, Marjanović A, Tomić A, Svetel M, Novaković I, Kostić VS

PMID: 27145302 [PubMed - indexed for MEDLINE]

19 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 2018/02/24

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.

[First cases of Pompe's disease in Kazakhstan].

Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(8):85-87

Authors: Zharkinbekova NA, Mukhambetova GA, Kaishibayeva GS, Zhiyenbayeva BS, Zhumagulova KB, Kaishibayev SN, Iglikova AE, Suleimanova SY

Abstract
The article presents the clinical observations of two newly diagnosed patients with Pompe disease in the Republic of Kazakhstan, confirmed by genetic research.

PMID: 28884723 [PubMed - indexed for MEDLINE]

MULTIMODAL IMAGING OF POSTERIOR POLAR ANNULAR CHOROIDAL DYSTROPHY.

Retin Cases Brief Rep. 2018 Winter;12(1):29-32

Authors: Forte R, Aptel F, Feldmann A, Chiquet C

Abstract
BACKGROUND: Posterior polar annular choroidal dystrophy (PPACD) is a rare disease. Patients with PPACD show loss of retinal pigment epithelium and choriocapillaries surrounding the vascular arcades and optic nerve.
METHODS: Two patients with PPACD were evaluated with multimodal imaging, including fundus autofluorescence (FAF) and adaptive optics (AO).
REPORT OF CASES: One patient (32 year old, one eye) with PPACD was followed up for 3 years. Best-corrected visual acuity (BCVA) was stable at 20/40, whereas a slight enlargement of paravascular atrophy of pigment epithelium was observed at fundus autofluorescence (FAF). Adaptive optics obtained at last examination showed reduced density of foveal cone photoreceptors. The second patient (30 year old, two eyes) with PPACD showed bilateral normal BCVA, associated with reduction in the density of foveal cone photoreceptors.
CONCLUSION: At FAF, longitudinal follow-up of PPACD showed progression of the paravascular atrophy of the pigment epithelium. Foveal cone photoreceptors can be reduced even in the presence of preserved visual acuity.

PMID: 27579567 [PubMed - indexed for MEDLINE]

Pachydermodactyly: A Benign Cutaneous Condition that May Be Misdiagnosed as a Joint Disorder.

J Rheumatol. 2016 08;43(8):1615-6

Authors: Chu H, Song J, Kim do Y

PMID: 27481990 [PubMed - indexed for MEDLINE]

New insights into the evaluation of randomized controlled trials for rare diseases over a long-term research horizon: a simulation study.

Stat Med. 2016 Aug 30;35(19):3245-58

Authors: Bayar MA, Le Teuff G, Michiels S, Sargent DJ, Le Deley MC

Abstract
Large sample sizes are required in randomized clinical trials designed to meet typical one-sided 2.5% α-level and 80% power. This may not be achievable when the disease is rare. We simulated a series of two-arm superiority trials over a 15-year period. The design parameters examined were the α-level and the number of trials conducted over the 15-year period (thus, trial sample size). Different disease severities and accrual rates were considered. The future treatment effect was characterized by its associated hazard rate; different hypotheses of how treatments improve over time were considered. We defined the total survival benefit as the relative difference of the hazard rates at year 15 versus year 0. The optimal design was defined by maximizing the expected total survival benefit, provided that the risk of selecting at year 15 a treatment inferior to the initial control treatment remains below 1%. Compared with two larger trials with typical one-sided 2.5% α-level, performing a series of small trials with relaxed α-levels leads on average to larger survival benefits over a 15-year research horizon, but also to higher risk of selecting a worse treatment at the end of the research period. Under reasonably optimistic assumptions regarding the future treatment effects, optimal designs outperform traditional ones when the disease is severe (baseline median survival ≤ 1 year) and the accrual is ≥100 patients per year, whereas no major improvement is observed in diseases with better prognosis. Trial designs aiming to maximize survival gain over a long research horizon across a series of trials are worth discussing in the context of rare diseases. Copyright © 2016 John Wiley & Sons, Ltd.

PMID: 27027783 [PubMed - indexed for MEDLINE]

Pediatric Pulmonology year in review 2016: Part 1.

Pediatr Pulmonol. 2017 Sep;52(9):1226-1233

Authors: Birnkrant DJ, Black JB, Tapia IE, Nicolai T, Gower WA, Noah TL

Abstract
Pediatric Pulmonology continues to publish research and clinical topics related to the entire range of children's respiratory disorders. As we have done annually in recent years, we here summarize the past year's publications in our major topic areas, as well as selected literature in these areas from other core journals relevant to our discipline. This review (Part 1) covers selected articles on sleep, diagnostic testing/endoscopy, respiratory complications of neuromuscular disorders, and rare lung diseases.

PMID: 28440921 [PubMed - indexed for MEDLINE]

A rare case of renal thrombotic microangiopathy associated with Castleman's disease.

BMC Nephrol. 2017 Feb 10;18(1):57

Authors: Mutneja A, Cossey LN, Liapis H, Chen YM

Abstract
BACKGROUND: Castleman's disease (CD) is an uncommon, heterogeneous lympho-proliferative disorder leading to high circulating levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). Renal involvement has been only described in a limited number of small studies. Herein, we report a rare case of renal thrombotic microangiopathy (TMA) associated with CD and investigate the podocyte expression of VEGF in the renal biopsy prior to initiation of treatment.
CASE PRESENTATION: An 18-year-old male presented with fever, diarrhea, diffuse lymphadenopathy, ascites and acute kidney injury. Laboratory tests for hemolytic uremic syndrome and thrombotic thrombocytopenic purpura were negative. The kidney biopsy showed TMA. An excisional lymph node biopsy was consistent with CD, plasma cell variant. Immunofluorescence staining showed suppressed podocyte VEGF expression. Chemotherapy that inhibits production of inflammatory mediators including IL-6 and VEGF led to complete recovery of renal function.
CONCLUSIONS: Our case illustrates a rare renal histological feature of CD. IL-6 and VEGF are postulated to suppress glomerular VEGF expression, thereby causing renal TMA. Therapy directed against these inflammatory mediators may have important therapeutic implications.

PMID: 28183278 [PubMed - indexed for MEDLINE]

[To reimburse or not? Evaluating expensive drugs differently].

Ned Tijdschr Geneeskd. 2016;160(0):D1022

Authors: Stolk J

Abstract
Health insurance organisations grant reimbursement for drug treatment on the basis of results of placebo-controlled randomised clinical trials showing a clinically meaningful and statistically significant effect over placebo. This often proves problematic in rare diseases as well as in many chronic diseases that are difficult to treat. Clinical scientists may address the issue by testing the drug on surrogate outcome parameters and ask for post-marketing studies conducted by expert reference centres as expediency research, using budgets provided by the government to show that the drug really works in terms of real-life patient experience. In the past 5 years, the pharmaceutical industry has released an increasing number of expensive drugs for rare diseases; this jeopardises the solidarity of health insurance cover for all EU citizens. To facilitate drug development, a new model might benefit all key players involved. The foundation Fair Medicine recently called for coalitions that jointly develop medicines based on contribution and complementarity, sharing responsibilities, risks and rewards.

PMID: 27879186 [PubMed - indexed for MEDLINE]

[Kleine Levin Syndrome: more than just periodic hypersomnia].

Ned Tijdschr Geneeskd. 2016;160:D238

Authors: Pillen S, Vandenbussche NL, Fronczek R, van Duijn J, Lammers GJ, Overeem S

Abstract
BACKGROUND: Kleine Levin Syndrome (KLS) is a rare disease with periodic hypersomnia as its main feature. Hyperphagia and hypersexuality are also described as classical symptoms, although quite recently it has become clear that the full triad is absent in the majority of patients.
CASE DESCRIPTION: A 14-year-old boy developed KLS after a period of flu-like symptoms. Over the course of three years he suffered from seven one-week episodes of extreme hypersomnia (sleeping 18 hours a day), depersonalisation, apathy, anxiety, paranoia, confusion, hallucinations and uninhibited sexual behaviour. He ate little. Ancillary investigations did not reveal any abnormalities. In between these episodes he had no symptoms.
CONCLUSION: From this case description and a summary of the symptoms of twelve other patients with KLS, it appears that neuropsychiatric symptoms are much more prominent than hyperphagia and hypersexuality. It is important that the typical KLS phenotype be reappraised, so that the condition can be recognised early and patients managed appropriately.

PMID: 27484420 [PubMed - indexed for MEDLINE]

FATCO Syndrome (Fibular Aplasia, Tibial Campomelia, Oligosyndactyly with Talar Aplasia). A Case Study.

Ortop Traumatol Rehabil. 2017 Jan 26;19(1):75-78

Authors: Ahmad K, Ahmad Malla H, Dawood S

Abstract
FATCO syndrome consists of fibular hemimelia, tibial campomelia and oligosyndactyly. FATCO syndrome can also be associated with other congenital anomalies; therefore, every case needs thorough evaluation so as to make the management of the patient easier. A few cases of this syndrome have been described in literature but only two cases have been reported in India so far. We present a 3-year-old male child born of a non-con-sanguinous marriage with FATCO syndrome and ipilateral talar aplasia without any other congenital anomalies.

PMID: 28436373 [PubMed - indexed for MEDLINE]

Evaluating the Calling Performance of a Rare Disease NGS Panel for Single Nucleotide and Copy Number Variants.

Mol Diagn Ther. 2017 Jun;21(3):303-313

Authors: Cacheiro P, Ordóñez-Ugalde A, Quintáns B, Piñeiro-Hermida S, Amigo J, García-Murias M, Pascual-Pascual SI, Grandas F, Arpa J, Carracedo A, Sobrido MJ

Abstract
INTRODUCTION: Variant detection protocols for clinical next-generation sequencing (NGS) need application-specific optimization. Our aim was to analyze the performance of single nucleotide variant (SNV) and copy number (CNV) detection programs on an NGS panel for a rare disease.
METHODS: Thirty genes were sequenced in 83 patients with hereditary spastic paraplegia. The variant calls obtained with LifeScope, GATK UnifiedGenotyper and GATK HaplotypeCaller were compared with Sanger sequencing. The calling efficiency was evaluated for 187 (56 unique) SNVs and indels. Five multiexon deletions detected by multiple ligation probe assay were assessed from the NGS panel data with ExomeDepth, panelcn.MOPS and CNVPanelizer software.
RESULTS: There were 48/51 (94%) SNVs and 1/5 (20%) indels consistently detected by all the calling algorithms. Two SNVs were not detected by any of the callers because of a rare reference allele, and one SNV in a low coverage region was only detected by two algorithms. Regarding CNVs, ExomeDepth detected 5/5 multi-exon deletions, panelcn.MOPs 4/5 and only 3/5 deletions were accurately detected by CNVPanelizer.
CONCLUSIONS: The calling efficiency of NGS algorithms for SNVs is influenced by variant type and coverage. NGS protocols need to account for the presence of rare variants in the reference sequence as well as for ambiguities in indel calling. CNV detection algorithms can be used to identify large deletions from NGS panel data for diagnostic applications; however, sensitivity depends on coverage, selection of the reference set and deletion size. We recommend the incorporation of several variant callers in the NGS pipeline to maximize variant detection efficiency.

PMID: 28290094 [PubMed - indexed for MEDLINE]

[The place of neuropathy in the early diagnosis of Cockayne syndrome: Report on two siblings].

Arch Pediatr. 2017 Apr;24(4):353-359

Authors: Blin-Rochemaure N, Allani-Essid N, Carlier R, Laugel V, Quijano-Roy S

Abstract
Two siblings affected with Cockayne syndrome (CS) are described: this diagnosis was suggested by the finding of a demyelinating neuropathy on electromyography in both children and consistent clinical features. CS is a rare genetic disorder with severe prognosis and a highly varied phenotype, making early diagnosis difficult. Taking into account these two cases and the literature, the current diagnosis criteria are insufficiently specific and appear late: the diagnosis may be delayed because multi-organ involvement and sensorial impairment suggests more frequent neurometabolic disorders. Neuroradiologic abnormalities are suggestive but may occur later. The finding of a demyelinating peripheral neuropathy seems to be a more useful marker to suspect this disorder in the presence of other clinical features. Further studies are required to better define the chronology of the symptoms, not only for adequate genetic counseling and eventual prenatal diagnosis, but also to assess the efficacy of future therapies.

PMID: 28258862 [PubMed - indexed for MEDLINE]

[Chronic vulvar lymphedema revealing Crohn disease in a teenage girl].

Arch Pediatr. 2017 Apr;24(4):346-349

Authors: Aounallah A, Ghariani Fetoui N, Ksiaa M, Boussofara L, Saidi W, Mokni S, Sriha B, Belajouza C, Denguezli M, Ghariani N, Nouira R

Abstract
INTRODUCTION: Cutaneous Crohn disease is a rare cutaneous manifestation of Crohn disease in children. Herein is reported a case of persistent vulvar lymphedema revealing Crohn disease in a teenage girl.
CASE REPORT: A 14-year-old girl presented with an 8-month history of persistent vulvar swelling associated with chronic macrocheilia. Dermatologic examination showed an inflammatory vulvar lymphedema, associated with perianal fissures and hypertrophic gingivitis. Vulvar skin biopsy revealed non-necrotizing granulomatous inflammation. Gastrointestinal endoscopy yielded no significant findings. The diagnosis of Crohn disease presenting as vulvar lymphedema was established. Oral metronidazole therapy resulted in partial improvement of cutaneous lesions beginning the 1st week.
CONCLUSION: The originality of this case lies in the presentation of chronic macrocheilia with persistent vulvar lymphedema in a child, revealing Crohn disease without gastrointestinal involvement.

PMID: 28233720 [PubMed - indexed for MEDLINE]