Lipoid Proteinosis: A Rare Disease In Pediatric Dentistry.

Braz Dent J. 2020 Mar-Apr;31(2):186-189

Authors: Lourenço AG, Araújo VC, Passador-Santos F, Sperandio M, Neville BW, Dorta RG

Abstract
This report describes the diagnostic process of a rare disorder in a Brazilian female child. The patient presented initially as a 7-year-old with multiple whitish submucosal nodules of a fibrous consistency in the lower lip, but with an inconclusive pathology report. When she turned 9 years of age, she presented with exacerbation of the original clinical findings, which then involved the upper lip, buccal mucosa, tongue and lingual frenulum. In addition, dermatological lesions were noted on the child's limbs and face, as well as a hoarse voice. Histopathological examination of the buccal mucosa revealed dense connective tissue with hyaline foci, which were positive with periodic acid-Schiff (PAS) staining and resistant to diastase digestion. Clinical and histopathological findings led to the diagnosis of a rare genetic disease with fewer than 300 reported cases - lipoid proteinosis. Magnetic resonance imaging revealed calcium deposits in her amygdaloid region of the brain, and nasopharyngolaryngoscopy revealed lesions in her vocal cords. The patient currently is stable and under multidisciplinary follow-up, but no treatment has been recommended to date.

PMID: 32556019 [PubMed - indexed for MEDLINE]

Isolated Bilateral Superior Rectii Paresis: A Rare Anomaly.

J Coll Physicians Surg Pak. 2019 Dec;29(12):1218-1220

Authors: Nadeem S

Abstract
We present a case of bilateral isolated superior rectus paresis in a 13-year girl who presented with alternating exotropia and hypertropia. She demonstrated bilateral paresis of elevation in abduction with an overaction of both the contralateral yoke muscles, i.e. inferior obliques. Neuroimaging did not reveal a lesion along the pathway of the third nerve nor hypoplasia of the superior rectus muscle. We performed a bilateral lateral rectus recession on adjustable sutures with bilateral myectomy of the inferior obliques (weakening of contralateral yoke muscle). At 1 year, the patient is well aligned and happy. Isolated extraocular muscle pareses are rare events, which present occasionally to the strabismus surgeons and need to be looked out for if the patient's strabismus looks peculiar. We believe we are the first to report an isolated paresis of the superior rectus muscle in Pakistan.

PMID: 31839100 [PubMed - indexed for MEDLINE]

Primary Intra-Osseous Basaloid Squamous Cell Carcinoma of Mandible: Report of Rare Case with Proposed Diagnostic Criteria.

J Coll Physicians Surg Pak. 2019 Dec;29(12):1215-1217

Authors: Bajpai M, Chandolia B, Pardhe N, Arora M

Abstract
Basaloid squamous cell carcinoma (BSCC) is a distinctive variant of squamous cell carcinoma (SCC) characterised by nests of basaloid cells. BSCC is an aggressive and rare tumor of head and neck region; and is relatively rare in oral cavity in comparison to SCC. Although, infrequent, but primary intra-osseous SCC (PIOSCC) has been reported in the jaws. There are separate diagnostic criteria for this lesion and a classification for primary intra-osseous carcinoma has been described. No evidence was found in the published literature about primary intra-osseous BSCC (PIOBSCC). We, herein, present a case of giant osteodestructive lesion of the posterior mandible which was diagnosed as PIOBSCC with a correlation of histopathological and immunohistochemical features. As per the best of our knowledge, this is the first case of PIOBSCC of the jaw. There is no diagnostic criterion of PIOBSCC in the literature owing to the extreme rarity of this tumor. A diagnostic criterion is proposed here to make the diagnosis of this tumor easier.

PMID: 31839099 [PubMed - indexed for MEDLINE]

Identification of Ezetimibe and Pranlukast as Pharmacological Chaperones for the Treatment of the Rare Disease Mucopolysaccharidosis Type IVA.

J Med Chem. 2019 07 11;62(13):6175-6189

Authors: Alméciga-Diaz CJ, Hidalgo OA, Olarte-Avellaneda S, Rodríguez-López A, Guzman E, Garzón R, Pimentel-Vera LN, Puentes-Tellez MA, Rojas-Rodriguez AF, Gorshkov K, Li R, Zheng W

Abstract
Mucopolysaccharidosis type IVA (MPS IVA) is a rare disease caused by mutations in the gene encoding the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). We report here two GALNS pharmacological chaperones, ezetimibe and pranlukast, identified by molecular docking-based virtual screening. These compounds bound to the active cavity of GALNS and increased its thermal stability as well as the production of recombinant GALNS in bacteria, yeast, and HEK293 cells. MPS IVA fibroblasts treated with these chaperones exhibited increases in GALNS protein and enzyme activity and reduced the size of enlarged lysosomes. Abnormalities in autophagy markers p62 and LC3B-II were alleviated by ezetimibe and pranlukast. Combined treatment of recombinant GALNS with ezetimibe or pranlukast produced an additive effect. Altogether, the results demonstrate that ezetimibe and pranlukast can increase the yield of recombinant GALNS and be used as a monotherapy or combination therapy to improve the therapeutic efficacy of MPS IVA enzyme replacement therapy.

PMID: 31188588 [PubMed - indexed for MEDLINE]

A potent antagonist antibody targeting connexin hemichannels alleviates Clouston syndrome symptoms in mutant mice.

EBioMedicine. 2020 Jun 12;:102825

Authors: Kuang Y, Zorzi V, Buratto D, Ziraldo G, Mazzarda F, Peres C, Nardin C, Salvatore AM, Chiani F, Scavizzi F, Raspa M, Qiang M, Chu Y, Shi X, Li Y, Liu L, Shi Y, Zonta F, Yang G, Lerner RA, Mammano F

Abstract
BACKGROUND: Numerous currently incurable human diseases have been causally linked to mutations in connexin (Cx) genes. In several instances, pathological mutations generate abnormally active Cx hemichannels, referred to also as "leaky" hemichannels. The goal of this study was to assay the in vivo efficacy of a potent antagonist antibody targeting Cx hemichannels.
METHODS: We employed the antibody to treat Cx30A88V/A88V adult mutant mice, the only available animal model of Clouston syndrome, a rare orphan disease caused by Cx30 p.A88V leaky hemichannels. To gain mechanistic insight into antibody action, we also performed patch clamp recordings, Ca2+ imaging and ATP release assay in vitro.
FINDINGS: Two weeks of antibody treatment sufficed to repress cell hyperproliferation in skin and reduce hypertrophic sebaceous glands (SGs) to wild type (wt) levels. These effects were obtained whether mutant mice were treated topically, by application of an antibody cream formulation, or systemically, by intraperitoneal antibody injection. Experiments with mouse primary keratinocytes and HaCaT cells revealed the antibody blocked Ca2+ influx and diminished ATP release through leaky Cx30 p.A88V hemichannels.
INTERPRETATION: Our results show anti-Cx antibody treatment was effective in vivo and sufficient to counteract the effects of pathological connexin expression in Cx30A88V/A88V mice. In vitro experiments suggest antibodies gained control over leaky hemichannels and contributed to restoring epidermal homeostasis. Therefore, regulating cell physiology by antibodies targeting the extracellular domain of Cxs may enforce an entirely new therapeutic strategy. These findings support the further development of antibodies as drugs to address unmet medical needs for Cx-related diseases. FUND: Fondazione Telethon, GGP19148; University of Padova, SID/BIRD187130; Consiglio Nazionale delle Ricerche, DSB.AD008.370.003\TERABIO-IBCN; National Science Foundation of China, 31770776; Science and Technology Commission of Shanghai Municipality, 16DZ1910200.

PMID: 32553574 [PubMed - as supplied by publisher]

Fine needle aspiration diagnosis of metastatic Leydig cell tumor. Report of a case and review of the literature.

J Am Soc Cytopathol. 2019 Jul - Aug;8(4):220-229

Authors: Biemer J, Pambuccian SE, Barkan GA

Abstract
Leydig cell tumors are rare sex cord-stromal tumors that account for less than 1% of all testicular tumors. Less than 10% of these tumors show metastatic malignant behavior. Herein we present a case of metastatic malignant Leydig cell tumor in an iliac lymph node diagnosed on fine-needle aspiration (FNA) in a 70-year-old man. The patient was referred from an outside institution with lymphadenopathy and had a past medical history of lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia and past surgical history of orchiectomy. An iliac lymph node FNA was performed demonstrating large discohesive plasmacytoid cells with indistinct cell borders; abundant and finely granular cytoplasm; round, eccentric nuclei with evenly distributed chromatin; and prominent nucleoli. The tumor cells were positive for inhibin and negative for calretinin and keratin leading to the diagnosis of metastatic malignant Leydig cell tumor. Review of the patient's history and of previous pathologic material, careful evaluation of cytomorphologic features, and the judicious use of immunohistochemistry can allow an accurate diagnosis of metastatic Leydig cell tumor.

PMID: 31272604 [PubMed - indexed for MEDLINE]

Fine-needle aspiration specimens of 3 cases of intra-abdominal Rosai-Dorfman disease with comprehensive review of the literature.

J Am Soc Cytopathol. 2019 Jul - Aug;8(4):190-205

Authors: McIntire PJ, Kilic AI, Chen HH, Atieh M, Wojcik EM, Pambuccian SE

Abstract
INTRODUCTION: Rosai-Dorfman disease (RDD) is a rare usually self-limited non-Langerhans cell histiocytosis of unknown etiology. Nodal and extranodal RDD appear to represent distinct conditions with different molecular alterations and prognosis. They also pose different diagnostic challenges on biopsies and fine-needle aspiration (FNA) cytology. The aim of this study was to report on 3 cases of intra-abdominal RDD and perform an extensive review of the literature on FNA findings of RDD.
MATERIALS AND METHODS: We reviewed FNA specimens from cases diagnosed histologically or cytologically as RDD during the past 10 years. We searched the PubMed and Google Scholar databases for cases of RDD sampled by FNA.
RESULTS: We identified 3 cases of intra-abdominal RDD, involving the kidney, periportal lymph node, and pancreas. FNA of the latter was hypocellular with fibrosis and was nondiagnostic. FNA of the first 2 yielded hypercellular smears that were diagnosed as RDD due to the identification of emperipolesis occurring in large uni- or binucleated histiocytes with large nuclei, fine chromatin, and prominent nucleoli in smears and cell-block sections. Immunohistochemistry showed positive staining for S100 and CD68 and negative staining for CD1a. The large histiocytes with emperipolesis were more difficult to identify histologically and their demonstration required immunohistochemical stains.
CONCLUSION: Our experience and an extensive review of the literature suggest that extranodal RDD can be diagnosed on FNA, and that the recognition of histiocytes with emperipolesis may be less challenging cytologically than histologically. The fibrosis frequently seen in extranodal RDD may lead to nondiagnostic aspirates, however.

PMID: 31272602 [PubMed - indexed for MEDLINE]

HTA programme response to the challenges of dealing with orphan medicinal products: Process evaluation in selected European countries.

Health Policy. 2019 02;123(2):140-151

Authors: Nicod E, Annemans L, Bucsics A, Lee A, Upadhyaya S, Facey K

Abstract
BACKGROUND: Challenges commonly encountered in HTA of orphan medicinal products (OMPs) were identified in Advance-HTA. Since then, new initiatives have been developed to specifically address issues related to HTA of OMPs.
OBJECTIVE AND METHODS: This study aimed to understand why these new HTA initiatives in England, Scotland and at European-level were established and whether they resolve the challenges of OMPs. The work of Advance-HTA was updated with a literature review and a conceptual framework of clinical, regulatory and economic challenges for OMPs was developed. The new HTA programmes were critiqued against the conceptual framework and outstanding challenges identified.
RESULTS: The new programmes in England and Scotland recognise the challenges identified in demonstrating the value of ultra-OMPs (and OMPs) and that they require a different process to standard HTA approaches. Wider considerations of disease and treatment experiences from a multi-stakeholder standpoint are needed, combined with other measures to deal with uncertainty (e.g. managed entry agreements). While approaches to assessing this new view of value of OMPs, extending beyond cost/QALY frameworks, differ, their criteria are similar. These are complemented by a European initiative that fosters multi-stakeholder dialogue and consensus about value determinants throughout the life-cycle of an OMP.
CONCLUSION: New HTA programmes specific to OMPs have been developed but questions remain about whether they sufficiently capture value and manage uncertainty in clinical practice.

PMID: 28400128 [PubMed - indexed for MEDLINE]

A Rare Cause of Misplaced Port Catheter: Episternal Ossicles With Abundant Fibrous Capsule.

Ann Thorac Surg. 2020 05;109(5):e391

Authors: Lee HY, Huang WL, Cheng LL, Huang LT

PMID: 31765615 [PubMed - indexed for MEDLINE]

NICE guideline for rectal cancer: already out of date.

Lancet. 2020 06 13;395(10240):e105-e106

Authors: Glynne-Jones R, Harrison M, Cheetham D

PMID: 32534652 [PubMed - indexed for MEDLINE]

Orthodontically Relevant Manifestations in People with Rare Diseases.

Med Princ Pract. 2019;28(3):216-221

Authors: Hanisch M, Hanisch L, Kleinheinz J, Danesh G, Benz K, Jackowski J

Abstract
BACKGROUND: Approximately 15% of all rare diseases occur with orofacial manifestations. Symptoms and manifestations of relevance to orthodontists represent a considerable proportion of these diseases and require appropriate strategies for their treatment. This article provides an overview of the orthodontically relevant manifestations of rare diseases.
MATERIAL AND METHODS: Overall, 3,639 rare diseases listed at the Orphanet, OMIM or Pubmed database were evaluated for orofacial manifestations. All rare diseases which were indicated with at least one orofacial manifestation were recorded in a database for rare diseases with orofacial manifestations called "ROMSE," which was developed by the authors. All the rare diseases were analysed with regard to orthodontically relevant orofacial manifestations, such as dysgnathia, changes in the number of teeth, failures of eruption, pathologies of bone metabolism or orofacial clefts. For all rare diseases with orthodontic relevance, an exact analysis was undertaken.
RESULTS: The orthodontically relevant orofacial manifestation termed dysgnathia is described in 151 of 535 identified rare diseases (28.2%). In these 151 rare diseases, 15 different subforms of dysgnathia, in the sense of skeletal misdevelopments of the jaws but without dental abnormalities, were described. Also changes in the number of teeth (17.9%), orofacial clefts (27.6%), failures of eruption (8.4%) and pathologies of the bone (2.1%) were described.
CONCLUSIONS: Orthodontics play an important role in the diagnosis and treatment of orofacial manifestations in rare diseases. Databases such as ROMSE are a first step toward providing valid information in publicly accessible databases.

PMID: 30716736 [PubMed - indexed for MEDLINE]

14 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 2020/06/17

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.

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 2020/06/13

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 2020/06/12

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 2020/06/11

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.

Role, function and challenges of multidisciplinary centres for rare diseases exemplified for neurofibromatosis type 1 syndrome.

Childs Nerv Syst. 2020 Jun 08;:

Authors: Toledano-Alhadef H, Mautner VF, Gugel I, Zipfel J, Haas-Lude K, Constantini S, Schuhmann MU

Abstract
PURPOSE: Neurofibromatosis type 1 (NF1) syndrome is a common rare/orphan disease that manifests itself early in the paediatric age. It imposes a considerable burden upon patients as well as on caregivers. Decisions regarding optimal care often rely on several medical instances working together as a team.
METHODS: The authors reviewed the literature and supplied a description of their own clinical work at the NF1 centres.
RESULTS: The experience of a multidisciplinary teamwork of three NF centres was summarized in order to enhance awareness for possible multidisciplinary ways of delivery of health and health-related aspects of care to NF1 patients. Both population-focused research centres and family-focused centres were reviewed.
CONCLUSIONS: Chronic rare diseases that start in the paediatric age mandate long-term follow-up most often by several disciplines. NF1 syndrome is an example of a multidisciplinary centre in order to enhance the quality of care.

PMID: 32514759 [PubMed - as supplied by publisher]

A human-on-a-chip approach to tackling rare diseases.

Drug Discov Today. 2019 11;24(11):2139-2151

Authors: de Mello CPP, Rumsey J, Slaughter V, Hickman JJ

Abstract
Drug development for rare diseases, classified as diseases with a prevalence of < 200 000 patients, is limited by the high cost of research and low target population. Owing to a lack of representative disease models, research has been challenging for orphan drugs. Human-on-a-chip (HoaC) technology, which models human tissues in interconnected in vitro microfluidic devices, has the potential to lower the cost of preclinical studies and increase the rate of drug approval by introducing human phenotypic models early in the drug discovery process. Advances in HoaC technology can drive a new approach to rare disease research and orphan drug development.

PMID: 31412288 [PubMed - indexed for MEDLINE]

Madelung Disease: Analysis of Clinicopathological Experience in Taipei Veterans General Hospital.

Ann Plast Surg. 2019 01;82(1S Suppl 1):S66-S71

Authors: Wan SC, Huang MH, Perng CK, Liao WC

Abstract
BACKGROUND: The main feature of Madelung disease (MD), a rare condition, is the growth of adipose tissue without a capsule. Usually, this disease is known for its prominent features with fat deposition around the neck, shoulder, back, or chest wall. Clinically, the patient is likely to exhibit alcohol, neuropathy, and metabolic disorders; however, no clear cause has been confirmed.
AIMS: The aim of this study was to analyze the morphological, pathophysiological, and various treatment methods of MD. We have presented and discussed 16 cases of treatment of this disease at our hospital and reviewed the literature on this subject.
METHODS: We carried out a retrospective chart review of 16 consecutive patients with MD treated from 1989 through 2017. Patient demographic data, tumor size and location, and follow-up data were evaluated. Patients usually seek treatment because of the disfigured appearance, restricted range of the motion of the head and neck, inconvenience in daily activity such as eating or speaking, and worry about the mass effect. All patients underwent surgical resection and/or combined liposuction.
RESULTS: Among the patients, 14 were men, aged 38 to 80 years, with a history of disease ranging from 6 months to 7 years. The mean duration from symptoms to diagnosis of MD was 4.4 years. The mean duration of follow-up was 82.8 months (range, 5-192 months). Three patients died of coronary artery disease at follow-up of 27, 78, and 141 months. The functional results were satisfactory in all patients. Severe complications were not observed.
CONCLUSIONS: According to our experience, surgical resection is the main method of improving the appearance, ensuring eradication of the tumor, and reducing the possibility of recurrence. In addition, we have a case in which atypical changes were confirmed by histological examination in fractional surgery. A long follow-up period is recommended considering the high propensity and mean time to recurrence. Although malignant transformation of MD is rare occurrence, it occurred in 1 of the 16 patients.

PMID: 30461459 [PubMed - indexed for MEDLINE]

18 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 2020/06/09

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.

18 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 2020/06/09

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.