Alveolar echinococcosis - a rare disease with differential diagnostic problems.

Rozhl Chir. Summer 2016;95(6):240-4

Authors: Třeška V, Kolářová L, Mírka H, Daum O, Matějů J, Liška V, Koubová A, Sedláček D

Abstract
INTRODUCTION: Alveolar echinococcosis is a life-threatening zoonotic parasitic disease. Its incidence is rare. In some cases, the correct and timely diagnosis can be difficult.
CASE REPORT: The authors present the case of a young patient with liver, diaphragm and lung involvement. The suspicion of echinococcus infection was made on the basis of medical history, clinical symptoms, and a combination of ultrasonography, computed tomography, magnetic resonance imaging tests and serological methods. The patient underwent multimodal treatment with albendazole and en-bloc resection of the liver, lung and diaphragm. The definitive diagnosis of alveolar echinococcosis was determined from samples of the resected tissues using histopathology and polymerase chain reaction methods. The patient has been followed regularly and is on life-long treatment with albendazole.
CONCLUSION: The precise diagnosis and multimodal therapy of alveolar echinococcosis is fundamental from the point of view of patient long-term survival.
KEY WORDS: alveolar echinococcosis - diagnosis - multimodal treatment - follow-up.

PMID: 27410758 [PubMed - indexed for MEDLINE]

Establishment and Maintenance of Primary Fibroblast Repositories for Rare Diseases-Friedreich's Ataxia Example.

Biopreserv Biobank. 2016 Aug;14(4):324-9

Authors: Li Y, Polak U, Clark AD, Bhalla AD, Chen YY, Li J, Farmer J, Seyer L, Lynch D, Butler JS, Napierala M

Abstract
Friedreich's ataxia (FRDA) represents a rare neurodegenerative disease caused by expansion of GAA trinucleotide repeats in the first intron of the FXN gene. The number of GAA repeats in FRDA patients varies from approximately 60 to <1000 and is tightly correlated with age of onset and severity of the disease symptoms. The heterogeneity of Friedreich's ataxia stresses the need for a large cohort of patient samples to conduct studies addressing the mechanism of disease pathogenesis or evaluate novel therapeutic candidates. Herein, we report the establishment and characterization of an FRDA fibroblast repository, which currently includes 50 primary cell lines derived from FRDA patients and seven lines from mutation carriers. These cells are also a source for generating induced pluripotent stem cell (iPSC) lines by reprogramming, as well as disease-relevant neuronal, cardiac, and pancreatic cells that can then be differentiated from the iPSCs. All FRDA and carrier lines are derived using a standard operating procedure and characterized to confirm mutation status, as well as expression of FXN mRNA and protein. Consideration and significance of creating disease-focused cell line and tissue repositories, especially in the context of rare and heterogeneous disorders, are presented. Although the economic aspect of creating and maintaining such repositories is important, the benefits of easy access to a collection of well-characterized cell lines for the purpose of drug discovery or disease mechanism studies overshadow the associated costs. Importantly, all FRDA fibroblast cell lines collected in our repository are available to the scientific community.

PMID: 27002638 [PubMed - indexed for MEDLINE]

Hereditary Sensory Autonomic Neuropathy II, a rare disease in a large Pakistani family.

J Pak Med Assoc. 2015 Oct;65(10):1128-30

Authors: Arain FM, Chand P

Abstract
Hereditary Sensory Autonomic Neuropathy II (HSAN II) is a rare genetic disorder, characterized by severe loss of pain, temperature and touch sensation. Injuries in these patients can progress to necrosis and shedding of digits and limbs. Here we report two cases of HSAN II belonging to a Pakistani family. Individual 1, a forty five year old man, had complete loss of pain sensation since birth. Self-mutilation and complication of injuries resulted in the shedding of all the digits and right foot and surgical amputation of left leg. Individual 2, a five year old girl,had delay in healing of wounds and self-mutilation. Examination showed a complete lack of pain sensation throughout her body and hyporeflexia. As the genetic cause of HSAN II is unknown, identification of more patients will allow further research on this disease and possibly develop a cure.

PMID: 26440849 [PubMed - indexed for MEDLINE]

A curated gene list for reporting results of newborn genomic sequencing.

Genet Med. 2017 Jan 12;:

Authors: Ceyhan-Birsoy O, Machini K, Lebo MS, Yu TW, Agrawal PB, Parad RB, Holm IA, McGuire A, Green RC, Beggs AH, Rehm HL

Abstract
PURPOSE: Genomic sequencing (GS) for newborns may enable detection of conditions for which early knowledge can improve health outcomes. One of the major challenges hindering its broader application is the time it takes to assess the clinical relevance of detected variants and the genes they impact so that disease risk is reported appropriately.
METHODS: To facilitate rapid interpretation of GS results in newborns, we curated a catalog of genes with putative pediatric relevance for their validity based on the ClinGen clinical validity classification framework criteria, age of onset, penetrance, and mode of inheritance through systematic evaluation of published evidence. Based on these attributes, we classified genes to guide the return of results in the BabySeq Project, a randomized, controlled trial exploring the use of newborn GS (nGS), and used our curated list for the first 15 newborns sequenced in this project.
RESULTS: Here, we present our curated list for 1,514 gene-disease associations. Overall, 954 genes met our criteria for return in nGS. This reference list eliminated manual assessment for 41% of rare variants identified in 15 newborns.
CONCLUSION: Our list provides a resource that can assist in guiding the interpretive scope of clinical GS for newborns and potentially other populations.Genet Med advance online publication 12 January 2017Genetics in Medicine (2017); doi:10.1038/gim.2016.193.

PMID: 28079900 [PubMed - as supplied by publisher]

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 2017/01/11

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.

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 2017/01/10

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.

4-HYDROXYNONENAL PROTEIN ADDUCTS: KEY MEDIATOR IN RETT SYNDROME OXINFLAMMATION.

Free Radic Biol Med. 2017 Jan 04;:

Authors: Valacchi G, Pecorelli A, Cervellati C, Hayek J

Abstract
In the last 15 years a strong correlation between oxidative stress (OxS) and Rett syndrome (RTT), a rare neurodevelopmental disorder known to be caused in 95% of the cases, by a mutation in the methyl-CpG-binding protein 2 (MECP2) gene, has been well documented. Here, we revised, summarized and discussed the current knowledge on the role of lipid peroxidation byproducts, with special emphasis on 4-hydroxynonenal (4HNE), in RTT pathophysiology. The posttranslational modifications of proteins via 4HNE, known as 4HNE protein adducts (4NHE-PAs), causing detrimental effects on protein functions, appear to contribute to the clinical severity of the syndrome, since their levels increase significantly during the subsequent 4 clinical stages, reaching the maximum degree at stage 4, represented by a late motor deterioration. In addition, 4HNE-PA are only partially removed due to the compromised functionality of the proteasome activity, contributing therefore to the cellular damage in RTT. All this will lead to a characteristic subclinical inflammation, defined "OxInflammation", derived by a positive feedback loop between OxS byproducts and inflammatory mediators that in a long run further aggravates the clinical features of RTT patients. Therefore, in a pathology completely orphan of any therapy, aiming 4HNE as a  therapeutic target could represent a coadjuvant treatment with some beneficial impact in these patients.‬‬‬.

PMID: 28063942 [PubMed - as supplied by publisher]

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 2017/01/07

PubMed comprises more than 24 million 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.

Mouse Models for Drug Discovery. Can New Tools and Technology Improve Translational Power?

ILAR J. 2016 Dec;57(2):178-185

Authors: Zuberi A, Lutz C

Abstract
The use of mouse models in biomedical research and preclinical drug evaluation is on the rise. The advent of new molecular genome-altering technologies such as CRISPR/Cas9 allows for genetic mutations to be introduced into the germ line of a mouse faster and less expensively than previous methods. In addition, the rapid progress in the development and use of somatic transgenesis using viral vectors, as well as manipulations of gene expression with siRNAs and antisense oligonucleotides, allow for even greater exploration into genomics and systems biology. These technological advances come at a time when cost reductions in genome sequencing have led to the identification of pathogenic mutations in patient populations, providing unprecedented opportunities in the use of mice to model human disease. The ease of genetic engineering in mice also offers a potential paradigm shift in resource sharing and the speed by which models are made available in the public domain. Predictively, the knowledge alone that a model can be quickly remade will provide relief to resources encumbered by licensing and Material Transfer Agreements. For decades, mouse strains have provided an exquisite experimental tool to study the pathophysiology of the disease and assess therapeutic options in a genetically defined system. However, a major limitation of the mouse has been the limited genetic diversity associated with common laboratory mice. This has been overcome with the recent development of the Collaborative Cross and Diversity Outbred mice. These strains provide new tools capable of replicating genetic diversity to that approaching the diversity found in human populations. The Collaborative Cross and Diversity Outbred strains thus provide a means to observe and characterize toxicity or efficacy of new therapeutic drugs for a given population. The combination of traditional and contemporary mouse genome editing tools, along with the addition of genetic diversity in new modeling systems, are synergistic and serve to make the mouse a better model for biomedical research, enhancing the potential for preclinical drug discovery and personalized medicine.

PMID: 28053071 [PubMed - in process]

Familial florid osseous dysplasia: a report with review of the literature.

BMJ Case Rep. 2016 Mar 30;2016:

Authors: Kucukkurt S, Rzayev S, Baris E, Atac MS

Abstract
There are three types of osseous dysplasia: periapical cemental dysplasia (PCD), focal cemento-osseous dysplasia (FCD) and florid osseous dysplasia (FOD). While PCD is often observed in mandibular anterior teeth, FCD mainly affects mandibular posterior teeth. FOD, on the other hand, commonly involves both jaws. FOD is a type of sclerosing disease that is characterised by intense opaque masses and many areas with different densities. Genetic heritance of FOD is unusual, with only a few reported cases. We describe a case of FOD that affected three family members, discuss its clinical, radiological and histological characteristics, and review the literature.

PMID: 27030456 [PubMed - indexed for MEDLINE]

IgG4-related mastitis, a rare disease, can radiologically and histologically mimic malignancy.

BMJ Case Rep. 2016 Mar 23;2016:

Authors: Yamada R, Horiguchi S, Yamashita T, Kamisawa T

Abstract
IgG4-related disease (IgG4-RD) is characterised by high serum concentrations of IgG4, dense lymphoplasmacytic infiltrates, storiform fibrosis and increased IgG4-positive plasma cells in tissues. This systemic disease occurs in various organs metachronously, but IgG4-related mastitis appears extremely rare. We report a case of IgG4-related mastitis, radiologically considered to represent breast cancer mainly composed of intraductal component and requiring histological differentiation from mucosa-associated lymphoid tissue (MALT) lymphoma. The breast mass disappeared with steroid therapy. When patients have a breast mass, regardless of the presence or absence of IgG4-RD, IgG4-related mastitis should be considered in addition to breast cancer. If histological findings show dense lymphoplasmacytic infiltrates, IgG4-related mastitis should be suspected in addition to malignant lymphoma, and lack of monoclonality should be confirmed. To avoid unnecessary surgery or chemotherapy, knowledge and accurate diagnosis of the entity of IgG4-related mastitis is necessary.

PMID: 27009197 [PubMed - indexed for MEDLINE]

B-cell lymphoma of the heart: A rare diagnosis.

Rev Port Cardiol. 2014 Dec;33(12):803.e1-3

Authors: Matos AP, Palas J, Doulaptsis C, Ramalho M, Duarte S, Bogaert J

Abstract
We present a case of a primary cardiac lymphoma in a 60-year-old woman. The clinical presentation was non-specific and the diagnosis was suggested by its appearance on multidetector computed tomography. The final diagnosis was achieved by histopathological study and was corroborated by a decrease in tumor volume after targeted chemotherapy. A brief review of the appearance of primary cardiac lymphomas in imaging studies is presented.

PMID: 25459635 [PubMed - indexed for MEDLINE]

Sjögren-Larsson syndrome: a rare disease of the skin and central nervous system.

BMJ Case Rep. 2016 Apr 19;2016:10.1136/bcr-2016-215110

Authors: Roy U, Das U, Pandit A, Debnath A

Abstract
Sjögren-Larsson syndrome is a recessively inherited disease caused by a deficiency of fatty aldehyde dehydrogenase with presenting features of congenital ichthyosis, spastic diplegia or tetraplegia, and mental retardation. The basic pathogenic mechanism is deficiency of fatty aldehyde dehydrogenase, which may lead to an accumulation of long-chain fatty alcohols hampering cell membrane integrity, which further disrupts the barrier function of skin and white matter of the brain. MRI of the brain shows diffuse symmetrical white matter hyperintensities on T2-weighted sequences. Although there is no definitive cure for Sjögren-Larsson syndrome, most patients survive until adulthood and management involves therapies directed towards controlling specific problems. We present a case of Sjögren-Larsson syndrome with classical clinical and MRI features, including a few distinctly atypical characteristics in various attributes.

PMID: 27095813 [PubMed - indexed for MEDLINE]

A rare complication resulting in a rare disease: radiation-induced male breast cancer.

BMJ Case Rep. 2016 Apr 15;2016:10.1136/bcr-2015-211874

Authors: Alazhri J, Saclarides C, Avisar E

Abstract
The increase in survival after childhood radiation therapy for some blood malignancies has led to an increase in the diagnosis of radiation-induced secondary solid malignancies (SSM). We report a young man presenting with invasive breast cancer 19 years after receiving radiation therapy and bone marrow transplant for acute lymphocytic leukaemia in childhood. This latency period is longer than previously reported. Therefore, survivors of radiation-treated primary cancer should be closely monitored for SSM, including breast cancer, for the rest of their lives.

PMID: 27084898 [PubMed - indexed for MEDLINE]

Overlapping 16p13.11 deletion and gain of copies variations associated with childhood onset psychosis include genes with mechanistic implications for autism associated pathways: Two case reports.

Am J Med Genet A. 2016 May;170A(5):1165-73

Authors: Brownstein CA, Kleiman RJ, Engle EC, Towne MC, D'Angelo EJ, Yu TW, Beggs AH, Picker J, Fogler JM, Carroll D, Schmitt RC, Wolff RR, Shen Y, Lip V, Bilguvar K, Kim A, Tembulkar S, O'Donnell K, Gonzalez-Heydrich J

Abstract
Copy number variability at 16p13.11 has been associated with intellectual disability, autism, schizophrenia, epilepsy, and attention-deficit hyperactivity disorder. Adolescent/adult- onset psychosis has been reported in a subset of these cases. Here, we report on two children with CNVs in 16p13.11 that developed psychosis before the age of 7. The genotype and neuropsychiatric abnormalities of these patients highlight several overlapping genes that have possible mechanistic relevance to pathways previously implicated in Autism Spectrum Disorders, including the mTOR signaling and the ubiquitin-proteasome cascades. A careful screening of the 16p13.11 region is warranted in patients with childhood onset psychosis.

PMID: 26887912 [PubMed - indexed for MEDLINE]

[Financing rare or orphan diseases].

Rev Peru Med Exp Salud Publica. 2014 Oct-Dec;31(4):808-9

Authors: Oyola-García A, Lituma-Aguirre D, Honorio-Morales H, Comisión Sectorial Enfermedades Raras o Huérfanas

PMID: 25597742 [PubMed - indexed for MEDLINE]

Once again, rare diseases provide a spotlight.

Mol Genet Metab. 2016 May;118(1):1-2

Authors: Lal TR, Borger DK, Sidransky E

PMID: 27017192 [PubMed - indexed for MEDLINE]

Fibrodysplasia Ossificans Progressiva.

J Coll Physicians Surg Pak. 2016 Feb;26(2):154-5

Authors: Rashid U, Bari A, Maqsood A, Naz S, Ahmad TM

Abstract
Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disorder characterized by postnatal progressive heterotopic ossification of connective tissue and congenital malformation of big toes. We report a 3-year male toddler with clinical and radiological features of FOP. He was born with bilateral hallux valgus and at the age of 3 years presented with hard swellings over back, scapular region and forehead that were initially inflammatory and then became bony hard. There is also tilting of neck towards the left due to calcification in neck region. The radiographs showed heterotopic ossification in thoracic region, neck, spine and region of hip joint.

PMID: 26876407 [PubMed - indexed for MEDLINE]

Atypical proliferative endometrioid tumor of ovary: Report of a rare case.

J Postgrad Med. 2016 Apr-Jun;62(2):129-32

Authors: Jetley S, Khetrapal S, Ahmad A, Jairajpuri ZS

Abstract
Borderline ovarian tumors represent 10-20% of epithelial ovarian neoplasms that typically have an excellent prognosis. Both the oncological behavior of this group of tumors and also the diagnostic histological criteria are intermediate between the specific criteria of benign and malignant. They usually occur in the third to fourth decade of women's lives and are limited to the ovary in 80% of cases. Atypical proliferative or borderline ovarian tumors constitute a group of epithelial tumors with an excellent prognosis due to the low aggressiveness, microscopic examination is mandatory in order to establish an accurate histological diagnosis in all cases of borderline ovarian tumors and to differentiate from well differentiated adenocarcinoma. We report a case of a 45 year old female who presented with irregular bleeding per vaginum and underwent hysterectomy with bilateral salpingo-oophorectomy. Atypical proliferative endometrioid tumor of the left ovary was an incidental finding, which is a very rare occurrence.

PMID: 26497398 [PubMed - indexed for MEDLINE]

Living with and treating rare diseases: experiences of patients and professional health care providers.

Qual Health Res. 2015 May;25(5):636-51

Authors: Garrino L, Picco E, Finiguerra I, Rossi D, Simone P, Roccatello D

Abstract
We explored the experiences of illness of patients suffering from rare diseases and of the health professionals who care for them at the Center for the Interregional Coordination of Rare Diseases of Piedmont and Valle d'Aosta in Italy. The research was carried out between 2010 and 2011. We collected qualitative data from 22 patients and 12 health professional health care providers. The interviews were analyzed using the Colaizzi phenomenological approach. We identified five themes from the narratives of the patient participants--dealing with disease development, living with the disease, everyday living, relating to others, and relations with health care providers--and four themes from the professional health care participants--dealing with the disease, dealing with expectations, building relationships, and being operators in the context. The study has raised awareness about the issue of rare diseases and it provides some useful considerations for improving services.

PMID: 25667160 [PubMed - indexed for MEDLINE]