Primary rhabdomyosarcoma of the distal femoral diaphysis: a case report and review of the literature.

Skeletal Radiol. 2016 Oct;45(10):1391-5

Authors: Bressner JA, McCarthy EF, Fayad LM, Morris CD

Abstract
Primary rhabdomyosarcoma of the bone is an extremely rare condition with few examples reported in the literature. We present the case of a 34-year-old male who presented with a lesion in the distal femur with initial imaging features consistent with Ewing sarcoma. Histologically, the lesion consisted of atypical pleomorphic polygonal rhabdomyoblasts demonstrating focal desmin and myogenin expression. A diagnosis of pleomorphic rhabdomyosarcoma was rendered. Despite systemic treatment and surgery, this patient experienced a rapidly progressive disease course. We believe this is only the second report in the orthopedic literature of a case of primary pleomorphic rhabdomyosarcoma of the bone. The key imaging, pathologic, and clinical findings are discussed.

PMID: 27412560 [PubMed - indexed for MEDLINE]

Treating the enigmatic "exceptional responders" as patients with undiagnosed diseases.

Sci Transl Med. 2016 05 25;8(340):340ed8

Authors: Perakslis ED, Kohane IS

PMID: 27225181 [PubMed - indexed for MEDLINE]

Collagenofibrotic glomerulopathy.

Kidney Int. 2016 06;89(6):1406

Authors: Patel S, Cimbaluk D

PMID: 27181787 [PubMed - indexed for MEDLINE]

11 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 2018/02/05

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.

11 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 2018/02/03

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.

Management of primary Sjögren's syndrome: recent developments and new classification criteria.

Ther Adv Musculoskelet Dis. 2018 Feb;10(2):39-54

Authors: Del Papa N, Vitali C

Abstract
For many years primary Sjögren's syndrome (pSS) has been considered an orphan disease, since no specific therapies were recognized as being capable of contrasting the development and progression of this disorder. The treatment of oral and ocular features, as well as of the systemic organ involvement, has been entrusted to the joint management of different subspecialty physicians, like ophthalmologists, otolaryngologists, dentists and rheumatologists. These latter subspecialty doctors are usually more involved in the treatment of systemic extraglandular involvement and, to do it, they have long been using the conventional therapies borrowed by the treatment schedules adopted in other systemic autoimmune diseases. The increasing knowledge of the biological pathways that are operative in patients with pSS, and the parallel development of molecular biology technology, have allowed the production and availability of a number of biological agents able to positively act on different disease mechanisms, and thus are candidates for testing in therapeutic trials. Meanwhile, the scientific community has made a great effort to develop new accurate and validated classification criteria and outcome measures to be applied in the selection of patients to be included and monitored in therapeutic studies. Some of the new-generation biotechnological agents have been tested in a number of open-label and randomized controlled trials that have produced in many cases inconclusive or contradictory results. Behind the differences in trial protocols, adopted outcome measures and predefined endpoints, reasons for such unsatisfactory results can be found in the large heterogeneity of clinical subtypes in the examined cohorts. The future challenge for a substantial advancement in the therapeutic approach to pSS could be to identify the pathologic mechanisms, outcome tools and biomarkers that characterize the different subsets of the disease in order to test carefully selected target therapies with the highest probability of success in each different clinical phenotype.

PMID: 29387177 [PubMed]

Management of intestinal failure in middle-income countries, for children and adults.

Curr Opin Organ Transplant. 2018 Jan 30;:

Authors: Gondolesi GE, Pattín F, Nikkoupur H

Abstract
PURPOSE OF REVIEW: Intestinal failure is a life-threatening medical condition that remains as a rare or orphan disease in most countries. The prevalence of intestinal failure and the therapeutic options available in middle-income countries (MIC) remain unclear. We aim to provide an overview on the current differences in management of intestinal failure patients in MIC from Latin America and Asia.
RECENT FINDINGS: In order to fulfil the challenge, and after facing the difficulties of going over a topic with scarce available data, from countries with an extreme variety of social and economic problems, which are closely related to the treatment of intestinal failure patients, we have used both the existing publications and personal surveys to draft this document. Our results have shown that there is still significant disparity among MIC over the last years, concepts such as the need for establishing multidisciplinary dedicated teams as well as the need to evolve first home parenteral nutrition (HPN), then rehabilitation, and finally transplantation, have become important signals of an adequate understanding of this evolving field.
SUMMARY: The manuscript presents, for the first time, an overview of the different developments and needs to manage intestinal failure patients in MIC from Latin America and Asia. Future discussions will emerge from this manuscript, aiming to pursue the development of registries, guidelines and health policies to continue improving the long-term care of intestinal failure patients in all MIC.

PMID: 29389822 [PubMed - as supplied by publisher]

The Association of Congenital Urethral Duplication and Double Megalourethra.

Balkan Med J. 2017 Dec 01;34(6):572-575

Authors: Uçar M, Karagözlü Akgül A, Kılıç N, Balkan E

Abstract
BACKGROUND: Urethral duplication and megalourethra are rare urethral anomalies. However, the concomitance of urethral duplication and double megalourethra has not been reported previously.
CASE REPORT: A newborn was presented with penile swelling during voiding. Physical examination revealed a retractable foreskin and two external meatus of a double urethra. Retrograde urethrography demonstrated two complete megalourethras. Urethro-urethrostomy and urethroplasty were performed when the patient was 10 months old. The patient was followed up for one year without any urinary problems and has good cosmetics and urinary continence.
CONCLUSION: The concomitance of these two rare anomalies and more importantly its surgical treatment makes this case report unique and valuable.

PMID: 29215339 [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 2018/01/31

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.

Gastric heterotopia in the rectum. A rare cause of ectopic gastric tissue.

Arab J Gastroenterol. 2017 Mar;18(1):42-43

Authors: Salem GA, Fazili J, Ali T

Abstract
Gastric heterotopia refers to the discovery of normal gastric tissue at foreign, unexpected sites. It has been described anywhere in the alimentary tract, even in the mediastinum, scrotum, and spinal cord. It is not uncommonly seen in the oesophagus or small intestine. However, large bowel lesions are rare, with the most common location of colonic lesions is the rectum. Although it is a rare entity, it may be the source for significant problems such as rectal bleeding, abdominal pain, deep rectal pain, and malignancy. Here, we report an additional case of gastric heterotopia in the rectum of a 56year old gentleman, and review the literature.

PMID: 28223104 [PubMed - indexed for MEDLINE]

Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease.

Proc Natl Acad Sci U S A. 2016 09 06;113(36):10127-32

Authors: Zhou Q, Yu X, Demirkaya E, Deuitch N, Stone D, Tsai WL, Kuehn HS, Wang H, Yang D, Park YH, Ombrello AK, Blake M, Romeo T, Remmers EF, Chae JJ, Mullikin JC, Güzel F, Milner JD, Boehm M, Rosenzweig SD, Gadina M, Welch SB, Özen S, Topaloglu R, Abinun M, Kastner DL, Aksentijevich I

Abstract
Systemic autoinflammatory diseases are caused by mutations in genes that function in innate immunity. Here, we report an autoinflammatory disease caused by loss-of-function mutations in OTULIN (FAM105B), encoding a deubiquitinase with linear linkage specificity. We identified two missense and one frameshift mutations in one Pakistani and two Turkish families with four affected patients. Patients presented with neonatal-onset fever, neutrophilic dermatitis/panniculitis, and failure to thrive, but without obvious primary immunodeficiency. HEK293 cells transfected with mutated OTULIN had decreased enzyme activity relative to cells transfected with WT OTULIN, and showed a substantial defect in the linear deubiquitination of target molecules. Stimulated patients' fibroblasts and peripheral blood mononuclear cells showed evidence for increased signaling in the canonical NF-κB pathway and accumulated linear ubiquitin aggregates. Levels of proinflammatory cytokines were significantly increased in the supernatants of stimulated primary cells and serum samples. This discovery adds to the emerging spectrum of human diseases caused by defects in the ubiquitin pathway and suggests a role for targeted cytokine therapies.

PMID: 27559085 [PubMed - indexed for MEDLINE]

Rare diseases: matching wheelchair users with rare metabolic, neuromuscular or neurological disorders to electric powered indoor/outdoor wheelchairs (EPIOCs).

Disabil Rehabil. 2016 Aug;38(16):1547-56

Authors: De Souza LH, Frank AO

Abstract
PURPOSE: To describe the clinical features of electric powered indoor/outdoor wheelchair (EPIOC) users with rare diseases (RD) impacting on EPIOC provision and seating.
METHOD: Retrospective review by a consultant in rehabilitation medicine of electronic and case note records of EPIOC recipients with RDs attending a specialist wheelchair service between June 2007 and September 2008. Data were systematically extracted, entered into a database and analysed under three themes; demographic, diagnostic/clinical (including comorbidity and associated clinical features (ACFs) of the illness/disability) and wheelchair factors.
RESULTS: Fifty-four (27 male) EPIOC users, mean age 37.3 (SD 18.6, range 11-70) with RDs were identified and reviewed a mean of 64 (range 0-131) months after receiving their wheelchair. Diagnoses included 27 types of RDs including Friedreich's ataxia, motor neurone disease, osteogenesis imperfecta, arthrogryposis, cerebellar syndromes and others. Nineteen users had between them 36 comorbidities and 30 users had 44 ACFs likely to influence the prescription. Tilt-in-space was provided to 34 (63%) users and specialised seating to 17 (31%). Four users had between them complex control or interfacing issues.
CONCLUSIONS: The complex and diverse clinical problems of those with RDs present unique challenges to the multiprofessional wheelchair team to maintain successful independent mobility and community living. Implications for Rehabilitation Powered mobility is a major therapeutic tool for those with rare diseases enhancing independence, participation, reducing pain and other clinical features. The challenge for rehabilitation professionals is reconciling the physical disabilities with the individual's need for function and participation whilst allowing for disease progression and/or growth. Powered wheelchair users with rare diseases with a (kypho) scoliosis require a wheelchair system that balances spine stability and movement to maximise residual upper limb and trunk function. The role of specialised seating needs careful consideration in supporting joint derangements and preventing complications such as pressure sores.

PMID: 26714619 [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 2018/01/27

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.

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 2018/01/27

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 primitive extratesticular seminoma: diagnosis of a rare pathology.

Acta Biomed. 2017 Apr 28;88(1):82-85

Authors: Saba L

Abstract
 Background: The Primitive Extratesticular Seminoma is a very rare condition and represents 3% of germ cell tumors; it is an indeterminate origin disease, whose diagnosis is often complicated by a nonspecific and highly variable clinical finding.
CASE PRESENTATION: A caucasian 55 years old male, non-smoker, arrived to our centre with cough, severe respiratory distress and dysphagia, in a context of the superior vena cava syndrome. A Computed Tomography was performed, which shows the presence of a mediastinal anterior mass with aorto-pulmonary window and left paracardiac invasion. A biopsy of the mediastinal mass was performed with mediastinoscopy; the hystological diagnosis was seminoma. After, first of all the 18FDG PET-CT is performed, which shows the presence of an intense hypermetabolism (SUV max=20.3 and metabolic volume 867 cc) at the level of bulky mediastinal mass, with paratracheal, aorto-pulmonary window and left paracardiac invasion. The mass presents also a sternal manubrium invasion. There were no other detectable tissue metabolic alterations with the 18FDG PET-CT and, in particular, the testicles examination was negative. A bilateral testicular ultrasound (US) was executed, which confirms the absence of testicular germ tumor. Clinical laboratory tests show a significant increase of beta-HCG (123 IU/L); AFP is negative. A final diagnosis of primitive extratesticular seminoma was carried.
CONCLUSIONS: The Primitive Extratesticolar Seminoma is a rare patology, and, for its massive size at the onset diagnosis, curable in early stage often only with radiochemotherapy. The Diagnostic Imaging and Nuclear Medicine, as Testicular Ultrasound, the CT with contrast medium and the 18FDG PET-CT total body examination, are fundamental to the staging and localisation. MRI sometimes is useful for testicular evaluation. The biopsy is needed for tissue characterization.

PMID: 28467339 [PubMed - indexed for MEDLINE]

Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features.

Proc Natl Acad Sci U S A. 2016 09 20;113(38):E5598-607

Authors: Ouyang Q, Nakayama T, Baytas O, Davidson SM, Yang C, Schmidt M, Lizarraga SB, Mishra S, Ei-Quessny M, Niaz S, Gul Butt M, Imran Murtaza S, Javed A, Chaudhry HR, Vaughan DJ, Hill RS, Partlow JN, Yoo SY, Lam AT, Nasir R, Al-Saffar M, Barkovich AJ, Schwede M, Nagpal S, Rajab A, DeBerardinis RJ, Housman DE, Mochida GH, Morrow EM

Abstract
Mutations that cause neurological phenotypes are highly informative with regard to mechanisms governing human brain function and disease. We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in large kindreds initially ascertained for intellectual and developmental disability (IDD). GPT2 [also known as alanine transaminase 2 (ALT2)] is one of two related transaminases that catalyze the reversible addition of an amino group from glutamate to pyruvate, yielding alanine and α-ketoglutarate. In addition to IDD, all affected individuals show postnatal microcephaly and ∼80% of those followed over time show progressive motor symptoms, a spastic paraplegia. Homozygous nonsense p.Arg404* and missense p.Pro272Leu mutations are shown biochemically to be loss of function. The GPT2 gene demonstrates increasing expression in brain in the early postnatal period, and GPT2 protein localizes to mitochondria. Akin to the human phenotype, Gpt2-null mice exhibit reduced brain growth. Through metabolomics and direct isotope tracing experiments, we find a number of metabolic abnormalities associated with loss of Gpt2. These include defects in amino acid metabolism such as low alanine levels and elevated essential amino acids. Also, we find defects in anaplerosis, the metabolic process involved in replenishing TCA cycle intermediates. Finally, mutant brains demonstrate misregulated metabolites in pathways implicated in neuroprotective mechanisms previously associated with neurodegenerative disorders. Overall, our data reveal an important role for the GPT2 enzyme in mitochondrial metabolism with relevance to developmental as well as potentially to neurodegenerative mechanisms.

PMID: 27601654 [PubMed - indexed for MEDLINE]

Risk of Human Papillomavirus Infection in Cancer-Prone Individuals: What We Know.

Viruses. 2018 Jan 20;10(1):

Authors: Khoury R, Sauter S, Butsch Kovacic M, Nelson AS, Myers KC, Mehta PA, Davies SM, Wells SI

Abstract
Human papillomavirus (HPV) infections cause a significant proportion of cancers worldwide, predominantly squamous cell carcinomas (SCC) of the mucosas and skin. High-risk HPV types are associated with SCCs of the anogenital and oropharyngeal tract. HPV oncogene activities and the biology of SCCs have been intensely studied in laboratory models and humans. What remains largely unknown are host tissue and immune-related factors that determine an individual's susceptibility to infection and/or carcinogenesis. Such susceptibility factors could serve to identify those at greatest risk and spark individually tailored HPV and SCC prevention efforts. Fanconi anemia (FA) is an inherited DNA repair disorder that is in part characterized by extreme susceptibility to SCCs. An increased prevalence of HPV has been reported in affected individuals, and molecular and functional connections between FA, SCC, and HPV were established in laboratory models. However, the presence of HPV in some human FA tumors is controversial, and the extent of the etiological connections remains to be established. Herein, we discuss cellular, immunological, and phenotypic features of FA, placed into the context of HPV pathogenesis. The goal is to highlight this orphan disease as a unique model system to uncover host genetic and molecular HPV features, as well as SCC susceptibility factors.

PMID: 29361695 [PubMed - in process]

Cerebral cortical neuron diversity and development at single-cell resolution.

Curr Opin Neurobiol. 2017 Feb;42:9-16

Authors: Johnson MB, Walsh CA

Abstract
Over a century of efforts to categorize the astonishing diversity of cortical neurons has relied on criteria of morphology, electrophysiology, ontology, and the expression of a few transcripts and proteins. The rapid development of single-cell RNA sequencing (scRNA-seq) adds genome-wide gene expression patterns to this list of criteria, and promises to reveal new insights into the transitions that establish neuronal identity during development, differentiation, activity, and disease. Comparing single neuron data to reference atlases constructed from hundreds of thousands of single-cell transcriptomes will be critical to understanding these transitions and the molecular mechanisms that drive them. We review early efforts, and discuss future challenges and opportunities, in applying scRNA-seq to the elucidation of neuronal subtypes and their development.

PMID: 27888678 [PubMed - indexed for MEDLINE]

Rare Disease: Lobar Holoprosencephaly With a Median Cleft Lip-Case Report.

Cleft Palate Craniofac J. 2016 Jan;53(1):109-17

Authors: Radojicic J, Tanic T, Pesic Z, Jovic N, Cutovic T, Filipovic G

Abstract
Holoprosencephaly is a complex malformation of the brain associated with the median facial defects. Variability of the clinical picture is the characteristic of this anomaly. In most cases, the degree of severity of the facial anomaly correlates with the degree of damage to the brain. This article aims to present a rare case of child with a milder form of brain anomaly combined with a severe form of facial anomaly. The article also presents the application of a feeding stimulator to improve the child's quality of life. The anomaly was diagnosed by postnatal sonography of the brain, magnetic resonance imaging of the endocranium, and three-dimensional computed tomography of the craniofacial skeleton.

PMID: 25291088 [PubMed - indexed for MEDLINE]

Early Recognition and Management of Rare Kidney Stone Disorders.

Urol Nurs. 2017 Mar-Apr;37(2):81-9, 102

Authors: Goldstein B, Goldfarb DS

Abstract
Kidney stones, especially those that present in childhood/adolescence, may be due to rare inherited disorders such as cystinuria. Early recognition and prompt treatment can help reduce or even prevent the serious long-term complications of these rare stone disorders.

PMID: 29240373 [PubMed - indexed for MEDLINE]