scholarly journals The Prevalence and Burden of Hypophosphatasia in an Ambulatory Endocrinology Practice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A269-A270
Author(s):  
Hugh B Quinn ◽  
Robert S Busch ◽  
Michael P Kane
Keyword(s):  
Renal Stones ◽  
High Serum ◽  
Loss Of Function ◽  
Text Search ◽  
Gene Encoding ◽  
Pain Medications ◽  
Wide Range ◽  
History Of ◽  
Mobility Impaired ◽  
Practice Methods

Abstract Introduction: Hypophosphatasia (HPP) is an autosomal disease resulting from loss-of-function mutations in the ALPL gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). The presentation and severity of the disease is highly variable ranging from perinatal-onset HPP with mortality rates as high as 100%, to adult onset with little mortality but with high disease-burden. Overall estimated prevalence of HPP in the general population is 1:100,000 though it may be significantly higher in specific populations. Hypophosphatasia is a heterogeneous disease that can reveal itself at any age, presenting within a wide range of symptoms. Adult HPP typically presents during middle age and is often misdiagnosed or missed in practice. The objective of this study was to determine the prevalence and burden of hypophosphatasia in an ambulatory care endocrinology practice. Methods: Potential subjects were identified via a computerized text search of the laboratory fields of patient electronic medical records (EMR). Search terms included serum ALP levels of less than or equal to 40 mg/dL. Records of patients with at least two low ALP levels were reviewed manually to identify potential patients with a history consistent with HPP. Results: A total of 315 patients with ALP levels < 40 mg/dL were identified via text search from an estimated 20,000 patient records. Fifty-six patients with a single low level were not considered for further review. The remaining 259 patients were reviewed for histories consistent with hypophosphatasia. These patients were predominantly white (64.9%), with an average age of 55 (+ 15) years, and an average BMI of 28 (+ 7) kg/m2. Ten of these patients had histories consistent with hypophosphatasia including musculoskeletal pain requiring scheduled use of pain medications, polyarthropathy, chondrocalcinosis, deformity secondary to fractures, low BMD, a history of nontraumatic fracture, delayed or incomplete fracture healing, a history of multiple orthopedic surgeries, fatigue, impaired mobility, impaired gait, impairment of daily activities, a history of renal stones or nephrocalcinosis, and/or high serum B6 levels. None of the identified ten patients were currently being treated or had previously been treated for hypophosphatasia and have subsequently been recommended for genetic testing. Conclusions: Hypophosphatasia is an uncommon condition with a highly variable presentation often resulting in a missed diagnosis. Surveillance of practices by identifying patients with low ALP levels is a reasonable screening approach to identifying potential patients with hypophosphatasia.

scholarly journals Genetic and Functional Investigation of Zn 2 Cys 6 Transcription Factors RSE2 and RSE3 in Podospora anserina

2013 ◽  
Vol 13 (1) ◽  
pp. 53-65 ◽  
Author(s):  
Elodie Bovier ◽  
Carole H. Sellem ◽  
Adeline Humbert ◽  
Annie Sainsard-Chanet
Keyword(s):  
Transcription Factors ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Constitutive Expression ◽  
Podospora Anserina ◽  
Loss Of Function ◽  
Gene Encoding ◽  
Content Type ◽  
Zinc Cluster ◽  
Wide Range ◽  
Genes Encoding

ABSTRACT In Podospora anserina , the two zinc cluster proteins RSE2 and RSE3 are essential for the expression of the gene encoding the alternative oxidase ( aox ) when the mitochondrial electron transport chain is impaired. In parallel, they activated the expression of gluconeogenic genes encoding phosphoenolpyruvate carboxykinase ( pck ) and fructose-1,6-biphosphatase ( fbp ). Orthologues of these transcription factors are present in a wide range of filamentous fungi, and no other role than the regulation of these three genes has been evidenced so far. In order to better understand the function and the organization of RSE2 and RSE3, we conducted a saturated genetic screen based on the constitutive expression of the aox gene. We identified 10 independent mutations in 9 positions in rse2 and 11 mutations in 5 positions in rse3 . Deletions were generated at some of these positions and the effects analyzed. This analysis suggests the presence of central regulatory domains and a C-terminal activation domain in both proteins. Microarray analysis revealed 598 genes that were differentially expressed in the strains containing gain- or loss-of-function mutations in rse2 or rse3 . It showed that in addition to aox , fbp , and pck , RSE2 and RSE3 regulate the expression of genes encoding the alternative NADH dehydrogenase, a Zn 2 Cys 6 transcription factor, a flavohemoglobin, and various hydrolases. As a complement to expression data, a metabolome profiling approach revealed that both an rse2 gain-of-function mutation and growth on antimycin result in similar metabolic alterations in amino acids, fatty acids, and α-ketoglutarate pools.

scholarly journals Association of parathyroid adenoma and familial hypocalciuric hypercalcaemia in a teenager

2009 ◽  
Vol 161 (1) ◽  
pp. 207-210 ◽  
Author(s):  
C Brachet ◽  
E Boros ◽  
S Tenoutasse ◽  
W Lissens ◽  
G Andry ◽  
...  
Keyword(s):  
Parathyroid Adenoma ◽  
Serum Calcium ◽  
Receptor Gene ◽  
Causal Link ◽  
Urinary Calcium ◽  
High Serum ◽  
Calcium Excretion ◽  
Loss Of Function ◽  
Mixed Family ◽  
History Of

ObjectiveFamilial hypocalciuric hypercalcaemia (FHH) is clinically characterized by mild to moderate parathyroid hormone (PTH)-dependent hypercalcaemia, autosomal dominant pattern of inheritance, and normal to frankly reduced urinary calcium excretion in spite of a high serum calcium (clearance (Ca)/clearance (Cr)<0.01). FHH has a benign course and should be differentiated from primary hyperparathyroidism. It is usually caused by a heterozygous loss-of-function mutation in the calcium-sensing receptor gene (CASR).DesignWe report the case of a 16-year-old patient with hypercalcaemia and a mixed family history of parathyroid adenoma and mild hypercalcaemia. Serum calcium was 14 mg/dl with a serum iPTH of 253 pg/ml.ResultsA neck 99mTc-sesta MIBI tomoscintigraphy showed a definite hyperactivity in the left upper quadrant. A surgical four-gland exploration confirmed a single parathyroid adenoma. After surgical resection of a left superior parathyroid adenoma, the patient's hypercalcemia improved but did not normalize, returning to a level typical of FHH. An inactivating mutation in exon 4 of the CASR gene, predicting a p.Glu297Lys amino acid substitution was found.ConclusionsThus, this 16-year old patient presented with the association of FHH and a single parathyroid adenoma. The young age of the patient and the association of parathyroid adenoma and FHH in his grandmother argue for a causal link between CASR mutation and parathyroid adenoma in this family. This case contributes to illustrate the expanding clinical spectrum of CASR loss-of-function mutations.

scholarly journals Case Report: A Novel TNFAIP3 Mutation Causing Haploinsufficiency of A20 With a Lupus-Like Phenotype

2021 ◽  
Vol 12 ◽  
Author(s):  
Zachary R. Shaheen ◽  
Sarah J. A. Williams ◽  
Bryce A. Binstadt
Keyword(s):  
Case Report ◽  
Early Onset ◽  
Autoinflammatory Disease ◽  
Clinical Symptoms ◽  
Novel Mutation ◽  
Genetic Mutations ◽  
Loss Of Function ◽  
Gene Encoding ◽  
Clinical Presentations ◽  
Wide Range

Genetic mutations that result in loss-of-function of the protein A20 result in an early-onset autoinflammatory disease—haploinsufficiency of A20 (HA20). The reported clinical presentations of HA20 include a Behcet’s disease-like phenotype and a more lupus-like phenotype. We have identified a novel mutation in the gene encoding A20 in a pediatric patient with chronic lymphadenopathy, lupus-like symptoms, and progressive hypogammaglobulinemia. This case illustrates the wide range of clinical symptoms, including immunodeficiency, that can occur in patients with HA20.

scholarly journals Biallelic loss-of-function OBSCN variants predispose individuals to severe, recurrent rhabdomyolysis

2021 ◽  
Author(s):  
Macarena Cabrera-Serrano ◽  
Laure Caccavelli ◽  
Marco Savarese ◽  
Anna Vihola ◽  
Manu Jokela ◽  
...  
Keyword(s):  
Genetic Disorders ◽  
Genetic Diagnosis ◽  
Allelic Loss ◽  
Loss Of Function ◽  
Gene Encoding ◽  
Lower Efficiency ◽  
Course Of Disease ◽  
Recurrent Rhabdomyolysis ◽  
History Of

Rhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety of genetic disorders predispose to rhabdomyolysis through different pathogenic mechanisms, particularly in patients with recurrent episodes. However, the majority of cases remain without a genetic diagnosis. Here we present six patients who presented with severe and recurrent rhabdomyolysis, usually with onset in the teenage years; other features included a history of myalgia and muscle cramps. We identified ten bi-allelic loss-of-function variants in the gene encoding obscurin (OBSCN) co-segregating with disease. We show reduced expression of OBSCN and loss of obscurin protein in patient muscle. Obscurin is proposed to be involved in SR function and Ca2+ handling. Patient cultured myoblasts appear more susceptible to starvation as evidenced by a greater decreased in SR Ca2+ content compared to control myoblasts. This likely reflects a lower efficiency when pumping Ca2+ back into the SR and/or a decrease in Ca2+ SR storage ability when metabolism is diminished. OSBCN variants have previously been associated with cardiomyopathies. None of the patients presented with a cardiomyopathy and cardiac examinations were normal in all cases in which cardiac function was assessed. There was also no history of cardiomyopathy in first degree relatives, in particular in any of the carrier parents. This cohort is relatively young, thus follow-up studies and the identification of additional cases with bi-allelic null OBSCN variants will further delineate OBSCN-related disease and the clinical course of disease.

scholarly journals Hereditary Hypercalcemia Caused by a Homozygous Pathogenic Variant in the CYP24A1 Gene: A Case Report and Review of the Literature

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Daniele Cappellani ◽  
Alessandro Brancatella ◽  
Martin Kaufmann ◽  
Angelo Minucci ◽  
Edda Vignali ◽  
...  
Keyword(s):  
Vitamin D ◽  
Gene Mutations ◽  
High Serum ◽  
Pathogenic Variant ◽  
Vitamin D Metabolites ◽  
Loss Of Function ◽  
Life Threatening ◽  
History Of ◽  
Granulomatous Diseases ◽  
Serum Pth

Introduction. Loss of function mutations of CYP24A1 gene, which is involved in vitamin D catabolism, cause vitamin D-mediated PTH-independent hypercalcemia. The phenotype varies from life-threatening forms in the infancy to milder forms in the adulthood. Case Presentation. We report a case of a 17-year-old woman with a history of nephrolithiasis, mild PTH-independent hypercalcemia (10,5mg/dL), and high serum 1,25(OH)2D concentrations (107pg/mL). Other causes of hypercalcemia associated with the above biochemical signature were excluded. Family history revealed nephrolithiasis in the sister. Blood testing in first-degree relatives showed serum PTH in the low-normal range and 1,25(OH)2D at the upper normal limit or slightly elevated. The CYP24A1 gene analysis revealed a known homozygous loss-of-function pathogenic variant (c.428_430delAAG, rs777676129, p.Glu143del). The panel of vitamin D metabolites evaluated by liquid chromatography showed the typical profile of CYP24A1 mutations, namely, low 24,25(OH)2D3, elevated 25(OH)D3:24,25(OH)2D3 ratio, and undetectable 1,24,25(OH)3D3. The parents and both the siblings harbored the same variant in heterozygosis. We decided for a watchful waiting approach and the patient remained clinically and biochemically stable over a 24-month followup. Conclusion. CYP24A1 gene mutations should be considered in cases of PTH-independent hypercalcemia, once that more common causes (hypercalcemia of malignancy, granulomatous diseases, and vitamin D intoxication) have been ruled out.

Group Experiences and Individual Differences in Stuttering

2019 ◽  
Vol 62 (12) ◽  
pp. 4335-4350 ◽  
Author(s):  
Seth E. Tichenor ◽  
J. Scott Yaruss
Keyword(s):  
Individual Differences ◽  
Support Groups ◽  
Support Group ◽  
Affective States ◽  
Life Outcomes ◽  
Self Help ◽  
Wide Range ◽  
Group Experiences ◽  
History Of ◽  
Adults Who Stutter

Purpose This study explored group experiences and individual differences in the behaviors, thoughts, and feelings perceived by adults who stutter. Respondents' goals when speaking and prior participation in self-help/support groups were used to predict individual differences in reported behaviors, thoughts, and feelings. Method In this study, 502 adults who stutter completed a survey examining their behaviors, thoughts, and feelings in and around moments of stuttering. Data were analyzed to determine distributions of group and individual experiences. Results Speakers reported experiencing a wide range of both overt behaviors (e.g., repetitions) and covert behaviors (e.g., remaining silent, choosing not to speak). Having the goal of not stuttering when speaking was significantly associated with more covert behaviors and more negative cognitive and affective states, whereas a history of self-help/support group participation was significantly associated with a decreased probability of these behaviors and states. Conclusion Data from this survey suggest that participating in self-help/support groups and having a goal of communicating freely (as opposed to trying not to stutter) are associated with less negative life outcomes due to stuttering. Results further indicate that the behaviors, thoughts, and experiences most commonly reported by speakers may not be those that are most readily observed by listeners.

Introduction: Emotion, History and the Arts

2018 ◽  
Vol 7 (2) ◽  
pp. 117-128 ◽  
Author(s):  
Erin Sullivan ◽  
Marie Louise Herzfeld-Schild
Keyword(s):  
Historical Change ◽  
Carson Mccullers ◽  
Emotional Life ◽  
Review Section ◽  
The Arts ◽  
Wide Range ◽  
War Correspondents ◽  
History Of ◽  
Johan Huizinga

This introduction surveys the rise of the history of emotions as a field and the role of the arts in such developments. Reflecting on the foundational role of the arts in the early emotion-oriented histories of Johan Huizinga and Jacob Burkhardt, as well as the concerns about methodological impressionism that have sometimes arisen in response to such studies, the introduction considers how intensive engagements with the arts can open up new insights into past emotions while still being historically and theoretically rigorous. Drawing on a wide range of emotionally charged art works from different times and places—including the novels of Carson McCullers and Harriet Beecher-Stowe, the private poetry of neo-Confucian Chinese civil servants, the photojournalism of twentieth-century war correspondents, and music from Igor Stravinsky to the Beatles—the introduction proposes five ways in which art in all its forms contributes to emotional life and consequently to emotional histories: first, by incubating deep emotional experiences that contribute to formations of identity; second, by acting as a place for the expression of private or deviant emotions; third, by functioning as a barometer of wider cultural and attitudinal change; fourth, by serving as an engine of momentous historical change; and fifth, by working as a tool for emotional connection across communities, both within specific time periods but also across them. The introduction finishes by outlining how the special issue's five articles and review section address each of these categories, while also illustrating new methodological possibilities for the field.

History of the Study of Apocrypha in Early Medieval England

2020 ◽  
Vol 48 (3-4) ◽  
pp. 13-26
Author(s):  
Brandon W. Hawk
Keyword(s):  
Old Testament ◽  
Medieval England ◽  
Medieval Period ◽  
Early Medieval ◽  
Future Directions ◽  
Early Judaism ◽  
Wide Range ◽  
History Of ◽  
The Subject ◽  
Early English

Literature written in England between about 500 and 1100 CE attests to a wide range of traditions, although it is clear that Christian sources were the most influential. Biblical apocrypha feature prominently across this corpus of literature, as early English authors clearly relied on a range of extra-biblical texts and traditions related to works under the umbrella of what have been called “Old Testament Pseudepigrapha” and “New Testament/Christian Apocrypha." While scholars of pseudepigrapha and apocrypha have long trained their eyes upon literature from the first few centuries of early Judaism and early Christianity, the medieval period has much to offer. This article presents a survey of significant developments and key threads in the history of scholarship on apocrypha in early medieval England. My purpose is not to offer a comprehensive bibliography, but to highlight major studies that have focused on the transmission of specific apocrypha, contributed to knowledge about medieval uses of apocrypha, and shaped the field from the nineteenth century up to the present. Bringing together major publications on the subject presents a striking picture of the state of the field as well as future directions.

FROM THE HISTORY OF THE FORMATION AND DEVELOPMENT OF PERIODICALS IN NAMANGAN

2019 ◽  
Vol 20 (2) ◽  
pp. 49-54
Author(s):  
Dildora Alinazarova ◽  
Keyword(s):  
The Past ◽  
Wide Range ◽  
History Of ◽  
Printing House

In this article, based on an analysis of a wide range of sources, discusses the emergence and development of periodicals and printing house in Namangan. The activities of Ibrat- as the founder of the first printing house in Namangan are considered. In addition, it describes the functioning and development of "Matbaai Ishokia" in the past and present

Young Scholars Conference “Slavic World: Commonality and Diversity”. 21–22 May 2019. Session “Linguistics”

2019 ◽  
Vol 14 (1-2) ◽  
pp. 295-297
Author(s):  
Sergej A. Borisov
Keyword(s):  
Czech Republic ◽  
Middle Ages ◽  
The Czech Republic ◽  
International Context ◽  
Slavic Languages ◽  
Russian Academy Of Sciences ◽  
Current State ◽  
Wide Range ◽  
History Of ◽  
Academy Of Sciences

For more than twenty years, the Institute of Slavic Studies of the Russian Academy of Sciences celebrates the Day of Slavic Writing and Culture with a traditional scholarly conference.”. Since 2014, it has been held in the young scholars’ format. In 2019, participants from Moscow, St. Petersburg, Kazan, Togliatti, Tyumen, Yekaterinburg, and Rostov-on-Don, as well as Slovakia, the Czech Republic, Hungary, and Romania continued this tradition. A wide range of problems related to the history of the Slavic peoples from the Middle Ages to the present time in the national, regional and international context were discussed again. Participants talked about the typology of Slavic languages and dialects, linguo-geography, socio- and ethnolinguistics, analyzed formation, development, current state, and prospects of Slavic literatures, etc.

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