Special Protocols for Special Patients.

EMS World. 2017 05;46(5):21-23, 25

Authors: Rubin M

PMID: 29989726 [PubMed - indexed for MEDLINE]

Osteoid osteoma of the pisiform bone: A rare cause of wrist pain.

Hand Surg Rehabil. 2016 09;35(4):296-298

Authors: Claeys R, Walsdorff M, Pargov S, Matasa R, Duttmann R, Cannie M

Abstract
Non-traumatic wrist pain remains a diagnostic challenge. An accurate diagnosis is crucial in order to choose the appropriate treatment. We report the case of a 23-year-old female with a four-month history of mainly nocturnal wrist pain. There was no history of trauma or prior surgery. Radiographs and CT scans showed a lytic lesion with central nidus and sclerotic margins in the pisiform bone. Bone scan showed increased uptake in the pisiform bone. The diagnosis of osteoid osteoma was confirmed by histopathological analysis after complete surgical resection. Osteoid osteoma of the carpal bones is a rare cause of wrist pain and can raise diagnostic issues. Diagnosis is based on both clinical and radiological features; histopathological analysis can confirm the diagnosis. Treatment depends on several criteria and multiple options are possible, but surgical excision is often preferred for the wrist. Osteoid osteoma should always be considered in young patients presenting with chronic unexplained wrist pain.

PMID: 27781996 [PubMed - indexed for MEDLINE]

Adult linear IgA bullous dermatosis: report of three cases.

An Bras Dermatol. 2018 Jun;93(3):435-437

Authors: Machado TYS, Enokihara MMSES, Iida TM, Porro AM

Abstract
Linear immunoglobulin A bullous dermatosis is a rare autoimmune disease that usually has an excellent prognosis in childhood; however, its control is more difficult in adults. It presents heterogeneous clinical manifestations and is frequently confused with other bullous diseases such as bullous pemphigoid and Duhring's dermatitis herpetiformis. Dermatologists' awareness of this disease contributes to early diagnosis and appropriate treatment. We thus report three cases of linear immunoglobulin A dermatosis in adults.

PMID: 29924252 [PubMed - indexed for MEDLINE]

[SOLAR URTICARIA].

Harefuah. 2016 Oct;155(10):604-607

Authors: Sabbah F, Hodak E, Levi A

Abstract
INTRODUCTION: Solar urticaria is a rare photodermatosis. It belongs to the group of physical urticarias. In this particular urticarial, erythema and whealing accompanied by pruritus occur seconds to minutes after exposure to light. The disease might have a severe impact on the patient's quality of life. A correct diagnosis is important in order to allow proper treatment, which is often challenging. A characteristic patient is described with a review of the epidemiology, clinical manifestations, etiology, diagnosis, treatment course and prognosis of this rare disease.

PMID: 28530058 [PubMed - indexed for MEDLINE]

Penile refracture: a preliminary report.

Int Braz J Urol. 2018 Jul-Aug;44(4):800-804

Authors: Barros R, Guimarães M, Nascimento C, Araújo LR, Koifman L, Favorito LA

Abstract
OBJECTIVE: To report our institutional experience with penile refracture, including demographic data, recurrence time, etiology and operative findings in the first and second episodes.
MATERIALS AND METHODS: Between January 1982 and September 2017, 281 patients underwent surgical treatment for penile fracture (PF) at our institution. Demographic data, clinical presentation, besides operative findings and follow-up of patients with relapsed PF were retrospectively assessed by reviewing medical records.
RESULTS: Of a total of 281 cases of PF operated at our institution, 3 (1.06%) patients experienced two episodes of trauma. Age ranged from 38 - 40 years (mean: 39.3). The recurrence time varied from 45 to 1560 days (mean: 705). Two patients presented the new fracture episode at the same site of the previous lesion, while in the other case the lesion was observed at another site.
CONCLUSION: Recurrent FP is an extremely rare entity. The risk factors for its occurrence are still unknown. Although the lesion of the corpus cavernosum ipsilateral to the scar tissue of the prior FP is more common, contralateral rupture may be present. Nevertheless, prospective studies with larger samples should be conducted.

PMID: 29757574 [PubMed - indexed for MEDLINE]

Mistletoe and Garlic Extracts as Polyurethane Carriers - A Possible Remedy for Choroidal Melanoma.

Curr Drug Deliv. 2017;14(8):1178-1188

Authors: Munteanu MF, Ardelean A, Borcan F, Trifunschi SI, Gligor R, Ardelean SA, Coricovac D, Pinzaru I, Andrica F, Borcan LC

Abstract
BACKGROUND: Melanoma is known as the most dangerous form of skin cancer; whereas the malignant choroidal melanoma is an orphan disease known as the most common primary intraocular malignancy in adults. Literature suggests that the consumption of garlic and mistletoe leads to a reduced risk of developing cancer.
OBJECTIVE: The aim of this study was the obtaining and the characterization of polymer structures containing mistletoe or garlic extract.
METHODS: The structures were obtained in a polyaddition process combined with a spontaneous emulsification; they were characterized by pH, size, Zeta potential and DSC measurements, evaluation of encapsulation efficacy, penetrability through membranes and in vitro cytotoxicity tests.
RESULTS: The microstructures present sizes between 1.05 and 2.60 µm and Zeta potentials between -7 and +36 mV. A good encapsulation was observed on different evaluations (88-92%). It was determined that approx. 30% of polymer microstructures containing vegetal extracts pass through an artificial membrane in 4 days. An in vitro cytotoxicity test revealed that these products are safe for administration. The analysis of antitumor efficacy indicates that garlic extracts have important effects after 48 and 72 hours on A375 cells; however, polymer microstructures with herbal extracts did not reveal antiproliferative activities on A375 cells because these polymer structures present a slow degradation.
CONCLUSION: Sterile eye drops solutions based on polymer microstructures containing garlic or mistletoe extracts were obtained; the sample based on garlic extracts may be used in the pharmaceutical field as drug carrier with an antiproliferative effect which occurs after a prolong period.

PMID: 28128068 [PubMed - indexed for MEDLINE]

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 2018/07/31

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.

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 2018/07/31

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.

Bilateral vision loss due to Leber's hereditary optic neuropathy after long-term alcohol, nicotine and drug abuse.

Doc Ophthalmol. 2018 04;136(2):145-153

Authors: Maass J, Matthé E

Abstract
PURPOSE: Leber's hereditary optic neuropathy is relatively rare, and no clinical pathognomonic signs exist. We present a rare case of bilateral vision loss of a patient with multiple drug abuse in the history.
OBSERVATION: A 31-year-old man presented with a history of progressive, decreased vision in both eyes for 6 month. On examination, his visual acuity was hand motion in both eyes. Funduscopy demonstrated a temporal pallor of the optic disc. Goldmann visual field perimetry showed a crescent visual field in the right eye and a circular decrease to less than 50 ° in the left eye. Electroretinogram showed a scotopic b-wave amplitude reduction. Optical coherence tomographies, Heidelberg Retina tomography, visual evoked potentials, and magnetic resonance imaging with contrast as well as blood tests were normal. The patient reported to consume various kinds of drugs as well as recreational drug use and alcohol consumption since he was 16 years old. We started a hemodilution therapy, believing the patient suffered from a bilateral, toxic optic neuropathy due to his lifestyle. Laboratory results later on showed Leber's hereditary optic neuropathy.
CONCLUSION AND IMPORTANCE: Leber's hereditary optic neuropathy is a rare disease without a typical, pathognomonic presentation. Even though the patient gave good reasons for a toxic optic neuropathy, one should never stop to test for other diseases.

PMID: 29372350 [PubMed - indexed for MEDLINE]

Matchmaker Exchange.

Curr Protoc Hum Genet. 2017 Oct 18;95:9.31.1-9.31.15

Authors: Sobreira NLM, Arachchi H, Buske OJ, Chong JX, Hutton B, Foreman J, Schiettecatte F, Groza T, Jacobsen JOB, Haendel MA, Boycott KM, Hamosh A, Rehm HL, Matchmaker Exchange Consortium

Abstract
In well over half of the individuals with rare disease who undergo clinical or research next-generation sequencing, the responsible gene cannot be determined. Some reasons for this relatively low yield include unappreciated phenotypic heterogeneity; locus heterogeneity; somatic and germline mosaicism; variants of uncertain functional significance; technically inaccessible areas of the genome; incorrect mode of inheritance investigated; and inadequate communication between clinicians and basic scientists with knowledge of particular genes, proteins, or biological systems. To facilitate such communication and improve the search for patients or model organisms with similar phenotypes and variants in specific candidate genes, we have developed the Matchmaker Exchange (MME). MME was created to establish a federated network connecting databases of genomic and phenotypic data using a common application programming interface (API). To date, seven databases can exchange data using the API (GeneMatcher, PhenomeCentral, DECIPHER, MyGene2, matchbox, Australian Genomics Health Alliance Patient Archive, and Monarch Initiative; the latter included for model organism matching). This article guides usage of the MME for rare disease gene discovery. © 2017 by John Wiley & Sons, Inc.

PMID: 29044468 [PubMed - indexed for MEDLINE]

The Rare Bone Disease Working Group: report from the 2016 American Society for Bone and Mineral Research Annual Meeting.

Bone. 2017 Sep;102:80-84

Authors: Drake MT, Collins MT, Hsiao EC

Abstract
A working group on rare bone diseases was held in Atlanta, Georgia as part of the 2016 annual meeting of the American Society for Bone and Mineral Research. The meeting was organized by Matthew Drake. Given recent advances in our understanding of fibrodysplasia ossificans progressiva (FOP), the initial portion of the program was devoted to basic, translational, and clinical aspects of FOP. The remainder of the program was divided into updates on an array of rare bone diseases as detailed below. In total, there were more than 120 scientists from academia and industry in attendance.

PMID: 28115283 [PubMed - indexed for MEDLINE]

Genomic approaches to diagnose rare bone disorders.

Bone. 2017 Sep;102:5-14

Authors: Falardeau F, Camurri MV, Campeau PM

Abstract
Skeletal dysplasias are Mendelian disorders with a prevalence of approximatively 1 in every 5000 individuals and can usually be diagnosed based on clinical and radiological findings. However, given that some diseases can be caused by several different genes, and that some genes can cause a variety of different phenotypes, achieving a molecular diagnosis can be challenging. We review here different approaches, from single gene sequencing to genomic approaches using next-generation sequencing, to reach a molecular diagnosis for skeletal dysplasias. We will further describe the overall advantages and limitations of first, second and third-generation sequencing, including single gene sequencing, whole-exome and genome sequencing (WES and WGS), multiple gene panel sequencing and single molecule sequencing. We also provide a brief overview of potential future applications of emerging technologies.

PMID: 27474525 [PubMed - indexed for MEDLINE]

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 2018/07/27

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.

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 2018/07/27

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.

Pressure Overload in Mice With Haploinsufficiency of Striated Preferentially Expressed Gene Leads to Decompensated Heart Failure.

Front Physiol. 2018;9:863

Authors: Shu C, Huang H, Xu Y, Rota M, Sorrentino A, Peng Y, Padera RF, Huntoon V, Agrawal PB, Liu X, Perrella MA

Abstract
Striated preferentially expressed gene (Speg) is a member of the myosin light chain kinase family of proteins. Constitutive Speg deficient (Speg-/-) mice develop a dilated cardiomyopathy, and the majority of these mice die in utero or shortly after birth. In the present study we assessed the importance of Speg in adult mice. Speg-/- mice that survived to adulthood, or adult striated muscle-specific Speg knockout mice (Speg-KO), demonstrated cardiac dysfunction and evidence of increased left ventricular (LV) internal diameter and heart to body weight ratio. To determine whether heterozygosity of Speg interferes with the response of the heart to pathophysiologic stress, Speg+/- mice were exposed to pressure overload induced by transverse aortic constriction (TAC). At baseline, Speg+/+ and Speg+/- hearts showed no difference in cardiac function. However, 4 weeks after TAC, Speg+/- mice had a marked reduction in LV function. This defect was associated with an increase in LV internal diameter and enhanced heart weight to body weight ratio, compared with Speg+/+ mice after TAC. The response of Speg+/- mice to pressure overload also included increased fibrotic deposition in the myocardium, disruption of transverse tubules, and attenuation in cell contractility, compared with Speg+/+ mice. Taken together, these data demonstrate that Speg is necessary for normal cardiac function and is involved in the complex adaptation of the heart in response to TAC. Haploinsufficiency of Speg results in decompensated heart failure when exposed to pressure overload.

PMID: 30042693 [PubMed]

Recommendations for the Management of Rare Kidney Cancers.

Eur Urol. 2017 Dec;72(6):974-983

Authors: Giles RH, Choueiri TK, Heng DY, Albiges L, Hsieh JJ, Linehan WM, Pal S, Maskens D, Paseman B, Jonasch E, Malouf G, Molina AM, Pickering L, Shuch B, Srinivas S, Srinivasan R, Tannir NM, Bex A

Abstract
CONTEXT: The European Association of Urology Renal Cell Carcinoma Guideline Panel recently conducted a systematic review of treatment options for patients with advanced non-clear-cell renal cell carcinomas (RCCs), which showed a substantial lack of evidence for management recommendations.
OBJECTIVE: To improve the outcomes of patients with rare kidney cancers (RKCs), we performed a subsequent unstructured review to determine current treatment strategies and druggable pathways, involving key stakeholders with a global perspective to generate recommendations.
EVIDENCE ACQUISITION: Based on the systematic review, literature was queried in Pubmed, Medline, and abstracts from proceedings of European Society for Medical Oncology and American Society of Clinical Oncology, in addition to consulting key opinion leaders and stakeholders. A conventional narrative review strategy was adopted to summarize the data.
EVIDENCE SYNTHESIS: The systematic review showed an absence of evidence for treating RKCs, with data only supporting sunitinib or MET inhibitors for some specific subtypes. However, a growing body of evidence implicates druggable pathways in specific RKC subtypes. To test hypotheses, the small patient numbers in each subtype require coordinated multicenter efforts. Many RKC patients are currently excluded from studies or are not analyzed using subtype-specific parameters, despite their unmet medical need.
CONCLUSIONS: We recognize the need for additional multicenter studies and subtype-specific analyses; however, we present management recommendations based on the data available. Web-based tools facilitating subtype-specific global registries and shared translational research resources will help generate sufficient data to formulate evidence-based recommendations for guidelines.
PATIENT SUMMARY: Patients confronted with rare kidney cancers are often treated the same way as clear-cell renal cell carcinoma patients, despite little evidence from randomized trials. Molecular characterization of tumors to stratify patients may improve outcomes. Availability of potential agents and trials remain a problem. Collaboration among medical centers is important to pool scarce data.

PMID: 28720391 [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 2018/07/24

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.

Orbitofrontal pseudotumour in young adult.

J Stomatol Oral Maxillofac Surg. 2018 Jul 19;:

Authors: Kulker D, Queiros C, Kun-Darbois JD, François P, Goga D, Paré A

Abstract
INTRODUCTION: Langerhans Cell Histiocytosis is an orphan disease of clonal dendritic cells that affect the facial skeleton in majority of cases. Actual management for unique and small lesion with easy access is surgical resection. Biggest lesion, with surgical risk is treated by association of vinblastine and corticotherapy. There is no case reported of corticotherapy as neoadjuvant treatment before the surgery for Langerhans Cell disease.
OBSERVATION: In this case, a man age of 18 presented a unifocal frontal bone injury, occasioning pain and skin inflammation in front of orbital lateral superior wall. The CT scan showed an important inflammation of soft tissues, and a heterogeneous osteolysis of the right frontal bone in contact with dura mater. A short corticotherapy was administered followed by a surgical curettage, with parietal bone graft reconstruction. During surgery, soft tissue inflammation wasn't found, and dura matter wasn't invaded. Histological examination confirmed the diagnostic of Histiocytosis. The treatment allowed symptoms resolve.
CONCLUSION: This case shows that corticotherapy doesn't negative histological examination in Langerhans Cell Histiocytosis and could facilitate its dissection and resection.

PMID: 30031893 [PubMed - as supplied by publisher]

5,10-methenyltetrahydrofolate synthetase deficiency causes a neurometabolic disorder associated with microcephaly, epilepsy, and cerebral hypomyelination.

Mol Genet Metab. 2018 Jun 15;:

Authors: Rodan LH, Qi W, Ducker GS, Demirbas D, Laine R, Yang E, Walker MA, Eichler F, Rabinowitz JD, Anselm I, Berry GT, Undiagnosed Diseases Network (UDN)

Abstract
Folate metabolism in the brain is critically important and serves a number of vital roles in nucleotide synthesis, single carbon metabolism/methylation, amino acid metabolism, and mitochondrial translation. Genetic defects in almost every enzyme of folate metabolism have been reported to date, and most have neurological sequelae. We report 2 patients presenting with a neurometabolic disorder associated with biallelic variants in the MTHFS gene, encoding 5,10-methenyltetrahydrofolate synthetase. Both patients presented with microcephaly, short stature, severe global developmental delay, progressive spasticity, epilepsy, and cerebral hypomyelination. Baseline CSF 5-methyltetrahydrolate (5-MTHF) levels were in the low-normal range. The first patient was treated with folinic acid, which resulted in worsening cerebral folate deficiency. Treatment in this patient with a combination of oral L-5-methyltetrahydrofolate and intramuscular methylcobalamin was able to increase CSF 5-MTHF levels, was well tolerated over a 4 month period, and resulted in subjective mild improvements in functioning. Measurement of MTHFS enzyme activity in fibroblasts confirmed reduced activity. The direct substrate of the MTHFS reaction, 5-formyl-THF, was elevated 30-fold in patient fibroblasts compared to control, supporting the hypothesis that the pathophysiology of this disorder is a manifestation of toxicity from this metabolite.

PMID: 30031689 [PubMed - as supplied by publisher]

Health-related quality of life among adults with diverse rare disorders.

Orphanet J Rare Dis. 2017 12 07;12(1):177

Authors: Bogart KR, Irvin VL

Abstract
BACKGROUND: Twenty-five to 30 million Americans live with a rare disease (RD) and share challenges unique to RD. The majority of research on RDs has focused on etiology, treatment and care, while the limited health-related quality of life (HRQL) research has been restricted to single RDs, small samples, or non-validated measures. This study reports HRQL among adults with diverse RDs, and compares their scores to those of the U.S. population and people with common chronic health conditions.
METHODS: We conducted a cross-sectional survey of adults living in the U.S. diagnosed with any RD. Participants were recruited through RD organizations and completed the online survey between December 2016 and May 2017 (n = 1218). HRQL was assessed using the standardized Patient-Reported Outcomes Measurement Information System (PROMIS). RDs were classified into categories defined by Orphanet. Means and 95% confidence intervals were calculated for the main sample and for RD categories and were compared to published U.S. population norms and common chronic disease norms. Intercorrelations were conducted between HRQL, demographics, and RD experiences.
RESULTS: When compared to the norms for the U.S. population and for those with common chronic diseases, mean HRQL scores were significantly poorer across all six PROMIS domains for the main sample, and were usually poorer when analyzed by sub-sets of specific RD classifications. People with rare systemic and rheumatologic, neurological, and immune diseases had the poorest HRQL. Participants had poorer HRQL if they had multiple RDs, lower income, were female, or older. Having symptoms longer was associated with worse HRQL, however, having a formal diagnosis longer was associated with better HRQL.
CONCLUSIONS: This study is the first to examine HRQL in a large, heterogeneous sample of RDs using validated measures. There is a significant disparity in HRQL among people with RD compared to the general population and people with common chronic diseases. Poor HRQL could be attributed to challenges accessing diagnoses, medical information, treatment, psychosocial support, and coping with stigma and uncertainty. As most individuals with RDs will not be cured in their lifetimes, identifying ways to improve HRQL is crucial to patient-centered care and should be a funding priority.

PMID: 29212508 [PubMed - indexed for MEDLINE]