Catecholamine-Induced Cardiomyopathy in Pheochromocytoma: How to Manage a Rare Complication in a Rare Disease?

Horm Metab Res. 2019 Jul;51(7):458-469

Authors: Santos JRU, Brofferio A, Viana B, Pacak K

Abstract
Pheochromocytomas and paragangliomas (PHEOs) are rare neuroendocrine tumors. Clinical manifestations include different cardiovascular signs and symptoms, which are related to excessive secretion of catecholamines. Catecholamine-induced cardiomyopathy in PHEO (CICMPP) is a rare but dreaded complication of PHEO. Once patient is diagnosed with this condition, the prognosis is worse and a surgical risk is much higher than expected. This article focuses on how catecholamines affect the heart and the pathophysiologic mechanism of CICMPP. The cardiovascular responses to catecholamine depend mostly on which catecholamine is released as well as the amount of catecholamine that is released. The acute release of norepinephrine and epinephrine from PHEO increases heart rate, systemic vascular resistance, myocardial contractility, and reduces venous compliance. The excessive adrenergic stimulation by catecholamine results in severe vasoconstriction and coronary vasospasm, myocardial ischemia, and subsequently damage, and necrosis. Chronically elevated catecholamine levels lead to significant desensitization of cardiac β-adrenoceptors. The increased levels of the enzyme β-adrenoceptors kinase (βARK) in the heart seems to mediate these biochemical and physiological changes that are consistently correlated with attenuated responsiveness to catecholamine stimulation. Through these mechanisms different types of cardiomyopathy (CMP) can be formed. This review discusses extensively the 3 types of cardiomyopathies that can be present in a PHEO patient. It also provides the clinical presentation and diagnostic and therapeutic algorithm in managing patients with CICMPP.

PMID: 30227459 [PubMed - indexed for MEDLINE]

Why Is This Auntminnie a Diagnostic Conundrum?: A Knowledge-Based Approach to Balo's Concentric Sclerosis From Reports of 3 Cases and Pooled Data From 68 Other Patients in the Literature.

Curr Probl Diagn Radiol. 2019 Jul - Aug;48(4):415-422

Authors: Agarwal M, Ulmer JL, Klein AP, Mark LP

Abstract
INTRODUCTION: We came across 3 cases of Balo's concentric sclerosis (BCS). The first of these patients presented to an outside hospital and was transferred to our institution due to complications resulting from a biopsy. The other 2 patients, despite having a characteristic imaging appearance and despite insistence on our part on the diagnosis of BCS, underwent a surgical procedure, which could have been prevented. This led us to review the available literature on BCS.
MATERIAL AND METHODS: A total of 68 patients diagnosed with BCS between 1995 and 2015 were studied and the data collected for the clinical presentation and course, imaging, spinal fluid analysis, treatment, and clinical and imaging outcome.
CONCLUSIONS: A 25% surgery rate (biopsy or resection) was found in the study. We concluded that this relatively high surgery rate in this auntminnie nonsurgical disease is multifactorial; and includes factors like nonfamiliarity with the disease, anxiety on the part of patients and physicians, due to a sometimes rapidly deteriorating clinical picture; and resemblance of the disease with other entities such as tumor and infection. However, characteristic imaging appearance combined with acute or subacute presentation and dramatic improvement in clinical status after high-dose steroid chemotherapy; are highly suggestive of the disease, and can prevent unnecessary surgery.

PMID: 29428181 [PubMed - indexed for MEDLINE]

Hibernoma: case report of a rare lipomatous tumor.

An Bras Dermatol. 2019 Sep - Oct;94(5):626-628

Authors: Valejo Coelho MM, João A, Fernandes C

PMID: 31777371 [PubMed - indexed for MEDLINE]

Newborn with desquamating rash.

J Fam Pract. 2019 Apr;68(3):175-177

Authors: Holmes N, Walker JJ, Chapple W

Abstract
A 9-day-old boy was brought to the emergency department by his mother. The infant had been doing well until his most recent diaper change when his mother noticed a rash around the umbilicus, genitalia, and anus. The infant was born at term via spontaneous vaginal delivery. The pregnancy was uncomplicated; the infant's mother was group B strep negative. Following a routine postpartum course, the infant underwent an elective circumcision before hospital discharge on his second day of life. There were no interval reports of irritability, poor feeding, fevers, vomiting, or changes in urine or stool output.

PMID: 31039216 [PubMed - indexed for MEDLINE]

Expanding the Boundaries of RNA Sequencing as a Diagnostic Tool for Rare Mendelian Disease.

Am J Hum Genet. 2019 03 07;104(3):466-483

Authors: Gonorazky HD, Naumenko S, Ramani AK, Nelakuditi V, Mashouri P, Wang P, Kao D, Ohri K, Viththiyapaskaran S, Tarnopolsky MA, Mathews KD, Moore SA, Osorio AN, Villanova D, Kemaladewi DU, Cohn RD, Brudno M, Dowling JJ

Abstract
Gene-panel and whole-exome analyses are now standard methodologies for mutation detection in Mendelian disease. However, the diagnostic yield achieved is at best 50%, leaving the genetic basis for disease unsolved in many individuals. New approaches are thus needed to narrow the diagnostic gap. Whole-genome sequencing is one potential strategy, but it currently has variant-interpretation challenges, particularly for non-coding changes. In this study we focus on transcriptome analysis, specifically total RNA sequencing (RNA-seq), by using monogenetic neuromuscular disorders as proof of principle. We examined a cohort of 25 exome and/or panel "negative" cases and provided genetic resolution in 36% (9/25). Causative mutations were identified in coding and non-coding exons, as well as in intronic regions, and the mutational pathomechanisms included transcriptional repression, exon skipping, and intron inclusion. We address a key barrier of transcriptome-based diagnostics: the need for source material with disease-representative expression patterns. We establish that blood-based RNA-seq is not adequate for neuromuscular diagnostics, whereas myotubes generated by transdifferentiation from an individual's fibroblasts accurately reflect the muscle transcriptome and faithfully reveal disease-causing mutations. Our work confirms that RNA-seq can greatly improve diagnostic yield in genetically unresolved cases of Mendelian disease, defines strengths and challenges of the technology, and demonstrates the suitability of cell models for RNA-based diagnostics. Our data set the stage for development of RNA-seq as a powerful clinical diagnostic tool that can be applied to the large population of individuals with undiagnosed, rare diseases and provide a framework for establishing minimally invasive strategies for doing so.

PMID: 30827497 [PubMed - indexed for MEDLINE]

"It is like a jungle gym, and everything is under construction": The parent's perspective of caring for a child with a rare disease.

Child Care Health Dev. 2019 01;45(1):96-103

Authors: Currie G, Szabo J

Abstract
DESCRIPTIVE TITLE: Parents of children with rare diseases face pervasive challenges in meeting medical and social care needs. Existing research on the parents' experience of caring for a child with a rare disease is limited. This paper offers suggestions for better supporting families living with rare disease as well as possible avenues of future research.
BACKGROUND: Parents of children with rare diseases face pervasive challenges in meeting medical and social care needs. Existing research on the parent's experience of caring for a child with a rare disease is limited.
METHODS: An interpretive phenomenological approach was applied in this inquiry. Fifteen parents of children with rare diseases participated in semistructured interviews.
RESULTS: Interpretive thematic analysis revealed that due to the rarity of the disease and an overall lack of knowledge of the disease, there is an increase in the burden on the family in relation to "rarity" in addition to "disability." Four insights were also revealed: (a) Parents often know more about the disease then Health Care providers, and this leads to entanglements in communication and collaboration as experts and parents; (b) there is lack of coordination of care between providers and services caring for children with rare diseases; (c) there is a gap in accessibility to government supports; and (d) due to fragmented care, parents must fill the aforementioned gaps by juggling multiple roles including that of advocate, case manager, and medical navigator.
CONCLUSION: This paper offers suggestions for better supporting families living with rare disease as well as possible avenues of future research.

PMID: 30370696 [PubMed - indexed for MEDLINE]

47 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 2019/12/18

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.

FDA oversight of NSIGHT genomic research: the need for an integrated systems approach to regulation.

NPJ Genom Med. 2019;4:32

Authors: Milko LV, Chen F, Chan K, Brower AM, Agrawal PB, Beggs AH, Berg JS, Brenner SE, Holm IA, Koenig BA, Parad RB, Powell CM, Kingsmore SF

Abstract
The National Institutes of Health (NIH) funded the Newborn Sequencing In Genomic medicine and public HealTh (NSIGHT) Consortium to investigate the implications, challenges, and opportunities associated with the possible use of genomic sequence information in the newborn period. Following announcement of the NSIGHT awardees in 2013, the Food and Drug Administration (FDA) contacted investigators and requested that pre-submissions to investigational device exemptions (IDE) be submitted for the use of genomic sequencing under Title 21 of the Code of Federal Regulations (21 CFR) part 812. IDE regulation permits clinical investigation of medical devices that have not been approved by the FDA. To our knowledge, this marked the first time the FDA determined that NIH-funded clinical genomic research projects are subject to IDE regulation. Here, we review the history of and rationale behind FDA oversight of clinical research and the NSIGHT Consortium's experiences in navigating the IDE process. Overall, NSIGHT investigators found that FDA's application of existing IDE regulations and medical device definitions aligned imprecisely with the aims of publicly funded exploratory clinical research protocols. IDE risk assessments by the FDA were similar to, but distinct from, protocol risk assessments conducted by local Institutional Review Boards (IRBs), and had the potential to reflect novel oversight of emerging genomic technologies. However, the pre-IDE and IDE process delayed the start of NSIGHT research studies by an average of 10 months, and significantly limited the scope of investigation in two of the four NIH approved projects. Based on the experience of the NSIGHT Consortium, we conclude that policies and practices governing the development and use of novel genomic technologies in clinical research urgently need clarification in order to mitigate potentially conflicting or redundant oversight by IRBs, NIH, FDA, and state authorities.

PMID: 31839987 [PubMed]

Pathophysiology and targets for treatment in hereditary galactosemia: A systematic review of animal and cellular models.

J Inherit Metab Dis. 2019 Dec 06;:

Authors: Haskovic M, Coelho AI, Bierau J, Vanoevelen JM, Steinbusch LKM, Zimmermann LJI, Villamor-Martinez E, Berry GT, Rubio-Gozalbo ME

Abstract
Since the first description of galactosemia in 1908 and despite decades of research, the pathophysiology is complex and not yet fully elucidated. Galactosemia is an inborn error of carbohydrate metabolism caused by deficient activity of any of the galactose metabolizing enzymes. The current standard of care, a galactose-restricted diet, fails to prevent long-term complications. Studies in cellular and animal models in the past decades have led to an enormous progress and advancement of knowledge. Summarizing current evidence in the pathophysiology underlying hereditary galactosemia may contribute to the identification of treatment targets for alternative therapies that may successfully prevent long-term complications. A systematic review of cellular and animal studies reporting on disease complications (clinical signs and/or biochemical findings) and/or treatment targets in hereditary galactosemia was performed. PubMed/MEDLINE, EMBASE, and Web of Science were searched, 46 original articles were included. Results revealed that Gal-1-P is not the sole pathophysiological agent responsible for the phenotype observed in galactosemia. Other currently described contributing factors include accumulation of galactose metabolites, UDP-hexose alterations and subsequent impaired glycosylation, ER stress, altered signaling pathways and oxidative stress. GALK inhibitors, UGP up-regulation, uridine supplementation, ER stress reducers, antioxidants and pharmacological chaperones have been studied, showing rescue of biochemical and/or clinical symptoms in galactosemia. Promising co-adjuvant therapies include antioxidant therapy and UGP up-regulation. This systematic review provides an overview of the scattered information resulting from animal and cellular studies performed in the past decades, summarizing the complex pathophysiological mechanisms underlying hereditary galactosemia and providing insights on potential treatment targets. This article is protected by copyright. All rights reserved.

PMID: 31808946 [PubMed - as supplied by publisher]

Clinical and genetic spectrum of an orphan disease MPAN: a series with new variants and a novel phenotype.

Neurol Neurochir Pol. 2019 Dec 05;:

Authors: Akçakaya NH, Haryanyan G, Mercan S, Sozer N, Ali A, Tombul T, Ozbek U, Uğur İşeri SA, Yapıcı Z

Abstract
INTRODUCTION: Pathogenic variations in C19orf12 are responsible for two allelic diseases: mitochondrial membrane protein-associated neurodegeneration (MPAN); and spastic paraplegia type 43 (SPG43). MPAN is an orphan disease, which presents with spasticity, dystonia, peripheral nerve involvement, and dementia. The pattern of iron accumulation on brain MRI may be a clue for the diagnosis of MPAN. SPG43, on the other hand, is characterised by progressive lower limb spasticity without brain iron accumulation. We here present clinical and genetic findings of MPAN patients with potentially pathogenic C19orf12 variants.
MATERIALS AND METHODS: Patients from 13 different families having progressive motor symptoms with irritative pyramidal signs and brain iron accumulation were screened for C19orf12 gene variants.
RESULTS: C19orf12 screening identified seven variants associated with MPAN in eight patients from seven families. We associated two pathogenic variants (c.24G > C; p.(Lys8Asn) and c.194G > A; p.(Gly65Glu)) with the MPAN phenotype for the first time. We also provided a genetic diagnosis for a patient with an atypical MPAN presentation. The variant c.32C > T; p.(Thr11Met), common to Turkish adult-onset MPAN patients, was also detected in two unrelated late-onset MPAN patients.
CONCLUSIONS: Genetic analysis along with thorough clinical analysis supported by radiological findings will aid the differential diagnosis of MPAN within the neurodegeneration with brain iron accumulation spectrum as well as other disorders including hereditary spastic paraplegia. Dystonia and parkinsonism may not be the leading clinical findings in MPAN patients, as these are absent in the atypical case. Finally, we emphasise that the existence of frameshifting variants may bias the age of onset toward childhood.

PMID: 31804703 [PubMed - as supplied by publisher]

Hot topics and current controversies in non-cystic fibrosis bronchiectasis.

Breathe (Sheff). 2019 Dec;15(4):286-295

Authors: Severiche-Bueno D, Gamboa E, Reyes LF, Chotirmall SH

Abstract
Non-cystic fibrosis bronchiectasis (NCFB) is a neglected and orphan disease with poor advances through the 20th century. However, its prevalence is rising and with this come new challenges for physicians. Few guidelines are available to guide clinicians on how to diagnose and manage patients with NCFB. Many areas of debate persist, and there is lack of consensus about research priorities most needed to advance patient care and improve clinical outcomes. In this review, we highlight the current hot topics in NCFB and present updated evidence to inform the critical areas of controversy.
Key points: Postural drainage, active cycle of breathing techniques and pulmonary rehabilitation are non-pharmacological treatment options that should be offered to all patients with non-cystic fibrosis bronchiectasis (NCFB).Eradication of Pseudomonas aeruginosa (PA) colonisation in patients without an acute exacerbation remains debatable.Sputum cultures are the leading and most readily available tool to detect patients with chronic colonisation by PA and should be performed in all patients with NCFB.Antibacterial monoclonal antibodies and vaccine studies have shown promising results in the prevention of chronic colonisation with PA and should stimulate new studies in NCFB.NCFB patients colonised with PA are at more risk of a rapid decline in lung function, worsening quality of life and more hospital admissions.Dual therapy is a promising option for the management of patients with PA-related exacerbations.Patients with PA-related exacerbations benefit from prolonged courses of antibiotics (i.e. 14 days) but emerging and future studies, including dual therapy, may show promising results with shorter courses.Endophenotyping bronchiectasis to address its inherent heterogeneity is a promising avenue for future investment and research.

PMID: 31803263 [PubMed]

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 2019/12/04

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 2019/12/04

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.

15 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 2019/11/30

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 2019/11/29

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 2019/11/28

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.

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 2019/11/28

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.

Australian Paediatric Surveillance Unit Annual Report 2018.

Commun Dis Intell (2018). 2019 Nov 18;43:

Authors: Nunez CA, Morris A, Teutsch SM, McGregor S, Brotherton J, Novakovic D, Rawlinson W, Jones CA, Thorley BR, Elliott EJ

Abstract

PMID: 31738868 [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 2019/11/26

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 2019/11/26

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.