Idiopathic follicular mucinosis in childhood.

An Bras Dermatol. 2020 Mar - Apr;95(2):268-270

Authors: Bauer FJ, Almeida JRP, Sementilli A, Mattos E Dinato SL

PMID: 32171541 [PubMed - indexed for MEDLINE]

Diffuse normolipemic plane xanthoma and hepatitis C: chance?

An Bras Dermatol. 2020 Mar - Apr;95(2):261-262

Authors: Souza MCC, Martins PHT, Vivian A, Luzzatto L

PMID: 32146013 [PubMed - indexed for MEDLINE]

Prevalence and practice for rare diseases in primary care: a national cross-sectional study in the USA.

BMJ Open. 2019 04 01;9(4):e027248

Authors: Jo A, Larson S, Carek P, Peabody MR, Peterson LE, Mainous AG

Abstract
OBJECTIVES: There are more than 7000 rare diseases in the USA, and they are prevalent in 8% of the population. Due to life-threatening risk and limited therapies, early detection and treatment are critical. The purpose of this study was to explore characteristics of visits for patients with rare diseases seen by primary care physicians (PCPs).
DESIGN: The study used a cross sectional study using a national representative dataset, the National Ambulatory Medical Care Survey for the years 2012-2014.
SETTING: Primary care setting.
PARTICIPANTS: Visits to PCPs (n=22 306 representing 354 507 772 office visits to PCPs).
PRIMARY OUTCOME MEASURES: Prevalence of rare diseases in visits of PCPs was the primary outcome. Bivariate analyses and logistic regression analyses were used to compare patients with rare diseases and those without rare diseases and examined characteristics of PCP visits for rare diseases and practice pattern.
RESULTS: Among outpatient visits to PCPs, rare diseases account for 1.6% of the visits. The majority of patients with rare diseases were established patients (93.0%) and almost half (49.0%) were enrolled in public insurance programmes. The time spent in visits for rare diseases (22.4 min) and visits for more common diseases (21.3 min) was not significantly different (p=0.09). In an adjusted model controlling for patient characteristics (age, sex, types of insurance, reason for this visit, total number of chronic disease, having a rare disease and established or new patient), patients with rare diseases were 52% more likely to be referred to another provider (OR 1.52, 95% CI, 1.01 to 2.28).
CONCLUSIONS: Visits for rare diseases are uncommon in primary care practice. Future research may help to explain whether this low level of management of rare diseases in primary care practice is consistent with a goal of a broad scope of care.

PMID: 30940763 [PubMed - indexed for MEDLINE]

Rare diseases: who pays which bill?

Cad Saude Publica. 2019 09 09;35(9):e00145719

Authors: Trajman A

PMID: 31508695 [PubMed - indexed for MEDLINE]

Reply to the letter from Beuy Joob and Viroj Wiwanitkit.

Eur J Cancer Prev. 2019 09;28(5):457

Authors: Ni Y, Du J, Yin X, Lu M

PMID: 31385842 [PubMed - indexed for MEDLINE]

Rare Lung Disease Research: National Heart, Lung, and Blood Institute's Commitment to Partnership and Progress.

Chest. 2019 09;156(3):438-444

Authors: Vuga LJ, Aggarwal NR, Reineck LA, Kalantari R, Banerjee K, Kiley J

PMID: 31121150 [PubMed - indexed for MEDLINE]

The Molecular Basis of Chemical Chaperone Therapy for Oculocutaneous Albinism Type 1A.

J Invest Dermatol. 2019 05;139(5):1143-1149

Authors: Teramae A, Kobayashi Y, Kunimoto H, Nakajima K, Suzuki T, Tsuruta D, Fukai K

Abstract
Oculocutaneous albinism (OCA) is an autosomal recessive disease characterized by the reduction or complete lack of melanin pigment in the skin, hair, and eyes. No effective treatment for OCA is available at present. OCA type 1 is caused by mutations that disrupt the function of tyrosinase (TYR), the rate-limiting enzyme of melanin synthesis. Recently, it was shown that tyrosinase in some patients with OCA type 1 mutation is retained in the endoplasmic reticulum and that its catalytic activity is lost, a phenomenon known as endoplasmic reticulum retention. However, to our knowledge, the intracellular localization of tyrosinase in Japanese patients with OCA type 1 missense mutations has not been reported. In this study, we first investigated the intracellular localization of Japanese OCA type 1A missense mutant tyrosinases using Western blotting and immunohistochemical staining. R77Q, R239W, D383N, and P431L mutant tyrosinases were retained in the endoplasmic reticulum, and H211Y mutant tyrosinase was partially transported to the Golgi apparatus. Second, we explored the possibility of chemical chaperone therapy for Japanese patients with OCA type 1A missense mutations and found that HeLa cells expressing P431L mutant tyrosinase have restored tyrosinase activity after treatment with a low-dose tyrosinase inhibitor, as a chemical chaperone, in a dose-dependent manner. These results provide the basis for a possible chemical chaperone therapy to recover tyrosinase activities in patients with OCA type 1A patients.

PMID: 30447237 [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 2020/05/07

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.

13 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 2020/05/06

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.

Bone Disease in Nephropathic Cystinosis: Beyond Renal Osteodystrophy.

Int J Mol Sci. 2020 Apr 28;21(9):

Authors: Machuca-Gayet I, Quinaux T, Bertholet-Thomas A, Gaillard S, Claramunt-Taberner D, Acquaviva-Bourdain C, Bacchetta J

Abstract
Patients with chronic kidney disease (CKD) display significant mineral and bone disorders (CKD-MBD) that induce significant cardiovascular, growth and bone comorbidities. Nephropathic cystinosis is an inherited metabolic disorder caused by the lysosomal accumulation of cystine due to mutations in the CTNS gene encoding cystinosin, and leads to end-stage renal disease within the second decade. The cornerstone of management relies on cysteamine therapy to decrease lysosomal cystine accumulation in target organs. However, despite cysteamine therapy, patients display severe bone symptoms, and the concept of "cystinosis metabolic bone disease" is currently emerging. Even though its exact pathophysiology remains unclear, at least five distinct but complementary entities can explain bone impairment in addition to CKD-MBD: long-term consequences of renal Fanconi syndrome, malnutrition and copper deficiency, hormonal disturbances, myopathy, and intrinsic/iatrogenic bone defects. Direct effects of both CTNS mutation and cysteamine on osteoblasts and osteoclasts are described. Thus, the main objective of this manuscript is not only to provide a clinical update on bone disease in cystinosis, but also to summarize the current experimental evidence demonstrating a functional impairment of bone cells in this disease and to discuss new working hypotheses that deserve future research in the field.

PMID: 32354056 [PubMed - in process]

The value of diagnostic testing for parents of children with rare genetic diseases.

Genet Med. 2019 12;21(12):2798-2806

Authors: Marshall DA, MacDonald KV, Heidenreich S, Hartley T, Bernier FP, Gillespie MK, McInnes B, Innes AM, Armour CM, Boycott KM

Abstract
PURPOSE: Exome sequencing (ES) can rapidly identify disease-causing variants responsible for rare, single-gene diseases, and potentially reduce the duration of the diagnostic odyssey. Our study examines how parents and families value ES.
METHODS: We developed a discrete choice experiment (DCE) survey that was administered to parents of children with rare diseases. The DCE included 14 choice tasks with 6 attributes and 3 alternatives. A valuation-space model was used to estimate willingness to pay, willingness to wait for test results, and minimum acceptable chance of a diagnosis for changes in each attribute.
RESULTS: There were n = 319 respondents of whom 89% reported their child had genetic testing, and 66% reported their child had a diagnosis. Twenty-six percent reported that their child had been offered ES. Parents were willing to pay CAD$6590 (US$4943), wait 5.2 years to obtain diagnostic test results, and accept a reduction of 3.1% in the chance of a diagnosis for ES compared with operative procedures.
CONCLUSION: Timely access to ES could reduce the diagnostic odyssey and associated costs. Before ES is incorporated routinely into care for patients with rare diseases in Canada and more broadly, there must be a clear understanding of its value to patients and families.

PMID: 31239560 [PubMed - indexed for MEDLINE]

Mapping the Human Exposome to Uncover the Causes of Breast Cancer.

Int J Environ Res Public Health. 2019 12 27;17(1):

Authors: Bessonneau V, Rudel RA

Abstract
Breast cancer is an important cause of morbidity and mortality for women, yet a significant proportion of variation in individual risk is unexplained. It is reasonable to infer that unexplained breast cancer risks are caused by a myriad of exposures and their interactions with genetic factors. Most epidemiological studies investigating environmental contribution to breast cancer risk have focused on a limited set of exposures and outcomes based on a priori knowledge. We hypothesize that by measuring a rich set of molecular information with omics (e.g., metabolomics and adductomics) and comparing these profiles using a case-control design we can pinpoint novel environmental risk factors. Specifically, exposome-wide association study approaches can be used to compare molecular profiles between controls and either breast cancer cases or participants with phenotypic measures associated with breast cancer (e.g., high breast density, chronic inflammation). Current challenges in annotating compound peaks from biological samples can be addressed by creating libraries of environmental chemicals that are breast cancer relevant using publicly available high throughput exposure and toxicity data, and by mass spectra fragmentation. This line of discovery and innovation will extend understanding of how environmental exposures interact with genetics to affect health, and provide evidence to support new breast cancer prevention strategies.

PMID: 31892107 [PubMed - indexed for MEDLINE]

A Planetary Health Lens for Rare Diseases in Refugee Populations and Innovating Systems Medicine Education.

OMICS. 2019 07;23(7):338-339

Authors: Ağırbaşlı D, Ağırbaşlı M

PMID: 31188084 [PubMed - indexed for MEDLINE]

Secondary haemophagocytic lymphohistiocytosis associated with metronidazole.

Postgrad Med J. 2019 Jul;95(1125):390

Authors: Iio K, Ariyama Y, Tomita H, Sakakibara H, Hataya H

PMID: 31123179 [PubMed - indexed for MEDLINE]

Eidikology: proposition for a new terminology for the science of rare diseases.

Postgrad Med J. 2019 Jul;95(1125):406

Authors: Ramos-Zaldívar HM

PMID: 31023747 [PubMed - indexed for MEDLINE]

Characterization of SETD1A haploinsufficiency in humans and Drosophila defines a novel neurodevelopmental syndrome.

Mol Psychiatry. 2020 Apr 28;:

Authors: Kummeling J, Stremmelaar DE, Raun N, Reijnders MRF, Willemsen MH, Ruiterkamp-Versteeg M, Schepens M, Man CCO, Gilissen C, Cho MT, McWalter K, Sinnema M, Wheless JW, Simon MEH, Genetti CA, Casey AM, Terhal PA, van der Smagt JJ, van Gassen KLI, Joset P, Bahr A, Steindl K, Rauch A, Keller E, Raas-Rothschild A, Koolen DA, Agrawal PB, Hoffman TL, Powell-Hamilton NN, Thiffault I, Engleman K, Zhou D, Bodamer O, Hoefele J, Riedhammer KM, Schwaibold EMC, Tasic V, Schubert D, Top D, Pfundt R, Higgs MR, Kramer JM, Kleefstra T

Abstract
Defects in histone methyltransferases (HMTs) are major contributing factors in neurodevelopmental disorders (NDDs). Heterozygous variants of SETD1A involved in histone H3 lysine 4 (H3K4) methylation were previously identified in individuals with schizophrenia. Here, we define the clinical features of the Mendelian syndrome associated with haploinsufficiency of SETD1A by investigating 15 predominantly pediatric individuals who all have de novo SETD1A variants. These individuals present with a core set of symptoms comprising global developmental delay and/or intellectual disability, subtle facial dysmorphisms, behavioral and psychiatric problems. We examined cellular phenotypes in three patient-derived lymphoblastoid cell lines with three variants: p.Gly535Alafs*12, c.4582-2_4582delAG, and p.Tyr1499Asp. These patient cell lines displayed DNA damage repair defects that were comparable to previously observed RNAi-mediated depletion of SETD1A. This suggested that these variants, including the p.Tyr1499Asp in the catalytic SET domain, behave as loss-of-function (LoF) alleles. Previous studies demonstrated a role for SETD1A in cell cycle control and differentiation. However, individuals with SETD1A variants do not show major structural brain defects or severe microcephaly, suggesting that defective proliferation and differentiation of neural progenitors is unlikely the single underlying cause of the disorder. We show here that the Drosophila melanogaster SETD1A orthologue is required in postmitotic neurons of the fly brain for normal memory, suggesting a role in post development neuronal function. Together, this study defines a neurodevelopmental disorder caused by dominant de novo LoF variants in SETD1A and further supports a role for H3K4 methyltransferases in the regulation of neuronal processes underlying normal cognitive functioning.

PMID: 32346159 [PubMed - as supplied by publisher]

Letter to the editor: Diagnosis of erythropoietic protoporphyria with severe liver injury - a case report.

World J Gastroenterol. 2019 08 14;25(30):4292-4293

Authors: Wensink D, Wagenmakers MA, Wilson JP, Langendonk JG

Abstract
Erythropoietic protoporphyria (EPP) is an extremely rare disease which is often unrecognized as diagnosis. In the recent article Lui et al describe a patient with a new diagnosis of EPP with severe liver injury. Approximately 5%-20% of patients with EPP develop liver manifestations. The most severe complication of EPP is an hepatic crisis, which is a medical emergency requiring urgent treatment. Intensive treatment should consist of (exchange) transfusions and preferably in a center that performs liver transplantations.

PMID: 31435180 [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 2020/04/29

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 2020/04/29

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.

16 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 2020/04/28

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.