scholarly journals A 9-Month-Old with Skeletal Abnormalities and a Consanguineous Sibling with Mucopolysaccharidosis IVA: The Role of Urinary Glycosaminoglycan Testing in Disease Diagnosis and Treatment Monitoring

2021 ◽  
Vol 14 ◽  
pp. 117954762199940
Author(s):  
Eric Goldman ◽  
Angela Vu ◽  
Kelly Dietz ◽  
Stefani N Thomas
Keyword(s):  
Autosomal Recessive ◽  
Disease Diagnosis ◽  
Lysosomal Storage ◽  
Mucopolysaccharidosis Iva ◽  
Enzyme Replacement ◽  
Mps Iva ◽  
Normal Urine

Mucopolysaccharidosis IVA (MPS IVA) is a rare autosomal recessive lysosomal storage disorder resulting from N-acetylgalactosamine-6-sulfatase (GALNS) deficiency that occurs in approximately 1 in 76 000 to 1 in 640 000 live births. Given that the diagnosis of MPS IVA relies heavily on the results of initial urine glycosaminoglycan (GAG) screening, cases that present with falsely normal urine GAG concentrations can delay the diagnosis and follow-up care for patients. This case study follows a patient diagnosed with MPS IVA at 9 months of age based on relation to a consanguineous 3-year-old sibling with MPS IVA and the use of direct enzyme activity analysis. Details regarding skeletal presentation and identification of genetic variants are presented along with data on follow-up urinary GAG monitoring during treatment with enzyme replacement therapy and treatment for a growth hormone disorder.

scholarly journals The Landscape of Mucopolysaccharidosis in Southern and Eastern European Countries: A Survey from 19 Specialistic Centers.

2021 ◽  
Author(s):  
Anna Tylki-Szymańska ◽  
Zsuzsanna Almássy ◽  
Violetta Christophidou Anastasiadou ◽  
Daniela Avdjieva-Tzavella ◽  
Ingeborg Barisic ◽  
...  
Keyword(s):  
European Countries ◽  
Eastern European ◽  
Survey Analysis ◽  
Lysosomal Storage ◽  
European Regions ◽  
Enzyme Replacement ◽  
European Guidelines ◽  
Mps Iva ◽  
Eastern European Countries

Abstract Background: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by defects in genes coding for different lysosomal enzymes which degrade glycosaminoglycans. Impaired lysosomal degradation causes cell dysfunction leading to progressive multiorgan involvement, disabling consequences and poor life expectancy. Enzyme replacement therapy (ERT) is now available for most MPS types, offering beneficial effects on disease progression and improving quality of life of patients. The landscape of MPS in Europe is not completely described and studies on availability of treatment show that ERT is not adequately implemented, particularly in Southern and Eastern Europe. In this study we performed a survey analysis in main specialist centers in Southern and Eastern European countries, to outline the landscape of disease management in the region and understand ERT implementation, with particular reference to MPS IVA.Results: 19 experts from 14 Southern and Eastern European countries in total responded to the survey. Results outlined a picture of MPS management in the region, with a high number of MPS patients managed in the centers and a high level of care. MPS II was the most prevalent followed by MPS IVA, with a particular high number of adult patients. The study particularly focused on management and treatment of MPS IVA patients. Adherence to current European Guidelines for follow-up of MPS IVA patients is generally adequate, although some important assessments are reported as difficult due to the lack of MPS skilled specialists. Availability of ERT in Southern and Eastern European countries is generally in line with other European regions, even though regulatory, organizational and reimbursement constrains are demanding. Conclusions: The landscape of MPS in Southern and Eastern European countries is generally comparable to that of other European regions on the epidemiology, treatment accessibility and follow up difficulties. However, issues limiting ERT availability and reimbursement should be simplified, to start treatment as early as possible and make it available for more patients. Besides, educational programs dedicated to specialists should be implemented, particularly for pediatricians, clinical geneticists, surgeons, anesthesiologists and neurologists.

scholarly journals Characterization of New Proteomic Biomarker Candidates in Mucopolysaccharidosis Type IVA

2020 ◽  
Vol 22 (1) ◽  
pp. 226
Author(s):  
Víctor J. Álvarez ◽  
Susana B. Bravo ◽  
Maria Pilar Chantada-Vazquez ◽  
Cristóbal Colón ◽  
María J. De Castro ◽  
...  
Keyword(s):  
Keratan Sulfate ◽  
Bone Lesions ◽  
Mucopolysaccharidosis Type ◽  
Lysosomal Storage ◽  
Protein Biomarkers ◽  
Enzyme Replacement ◽  
Endurance Tests ◽  
Mps Iva ◽  
Mucopolysaccharidosis Type Iva ◽  
Potential Biomarkers

Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal storage disease caused by mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. Skeletal dysplasia and the related clinical features of MPS IVA are caused by disruption of the cartilage and its extracellular matrix, leading to a growth imbalance. Enzyme replacement therapy (ERT) with recombinant human GALNS has yielded positive results in activity of daily living and endurance tests. However, no data have demonstrated improvements in bone lesions and bone grow thin MPS IVA after ERT, and there is no correlation between therapeutic efficacy and urine levels of keratan sulfate, which accumulates in MPS IVA patients. Using qualitative and quantitative proteomics approaches, we analyzed leukocyte samples from healthy controls (n = 6) and from untreated (n = 5) and ERT-treated (n = 8, sampled before and after treatment) MPS IVA patients to identify potential biomarkers of disease. Out of 690 proteins identified in leukocytes, we selected a group of proteins that were dysregulated in MPS IVA patients with ERT. From these, we identified four potential protein biomarkers, all of which may influence bone and cartilage metabolism: lactotransferrin, coronin 1A, neutral alpha-glucosidase AB, and vitronectin. Further studies of cartilage and bone alterations in MPS IVA will be required to verify the validity of these proteins as potential biomarkers of MPS IVA.

scholarly journals A charitable access program for patients with lysosomal storage disorders in underserved communities worldwide

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Atul Mehta ◽  
Uma Ramaswami ◽  
Joseph Muenzer ◽  
Roberto Giugliani ◽  
Kurt Ullrich ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Clinical Manifestations ◽  
Lysosomal Storage Disorders ◽  
Expert Committee ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Access Program ◽  
Storage Disorders

Abstract Background Lysosomal storage disorders (LSDs) are rare genetic disorders, with heterogeneous clinical manifestations and severity. Treatment options, such as enzyme replacement therapy (ERT), substrate replacement therapy, and pharmacological chaperone therapy, are available for several LSDs, including Gaucher disease (GD), Fabry disease (FD), and Hunter syndrome (mucopolysaccharidosis type II [MPS II]). However, patients in some countries face challenges accessing treatments owing to limited availability of locally licensed, approved drugs. Methods The Takeda LSD Charitable access program aims to meet the needs of individuals with GD, FD or MPS II with the greatest overall likelihood of benefit, in selected countries, through donation of ERT to nonprofit organizations, and support for medical capacity-building as well as family support via independent grants. Long-term aims of the program are to establish sustainable healthcare services delivered by local healthcare providers for patients with rare metabolic diseases. Patients receiving treatment through the program are monitored regularly, and their clinical data and progress are reviewed annually by an independent medical expert committee (MEC). The MEC also selects patients for enrollment completely independent from the sponsoring company. Results As of 31 August, 2019, 199 patients from 13 countries were enrolled in the program; 142 with GD, 41 with MPS II, and 16 with FD. Physicians reported improvements in clinical condition for 147 (95%) of 155 patients with follow-up data at 1 year. Conclusions The response rate for follow-up data at 1 year was high, with data collected for > 90% of patients who received ERT through the program showing clinical improvements in the majority of patients. These findings suggest that the program can benefit selected patients previously unable to access disease-specific treatments. Further innovative solutions and efforts are needed to address the challenges and unmet needs of patients with LSDs and other rare diseases around the world.

Individualized Behavioural Treatment of Severe Stuttering

1991 ◽  
Vol 19 (4) ◽  
pp. 347-357 ◽  
Author(s):  
Willi Ecker ◽  
Victor Meyer
Keyword(s):  
Oral Reading ◽  
Reading Improvement ◽  
Behavioural Treatment ◽  
Communication Situations ◽  
Cognitive Techniques ◽  
One Year

This case study illustrates the reduction of severe stuttering by an individually tailored treatment programme. Interventions are derived from a tripartite analysis (Lang, 1971) and include EMG biofeedback, regulated breathing, exposure in vivo to stressful communication situations and cognitive techniques to reduce relapse risk. The role of dysfunctional response system interactions in stuttering is emphasized. Treatment resulted in a marked reduction of stuttering and associated facial contortions during videotaped conversations with strangers and oral reading. Improvement was maintained at one-year follow-up.

scholarly journals Immune response to enzyme replacement therapies in lysosomal storage diseases and the role of immune tolerance induction

2016 ◽  
Vol 117 (2) ◽  
pp. 66-83 ◽  
Author(s):  
Priya S. Kishnani ◽  
Patricia I. Dickson ◽  
Laurie Muldowney ◽  
Jessica J. Lee ◽  
Amy Rosenberg ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Tolerance ◽  
Tolerance Induction ◽  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Immune Tolerance Induction ◽  
Storage Diseases ◽  
Enzyme Replacement

scholarly journals Chest CT as a Complement to RT-PCR to Confirm and Follow-up COVID-19 Patients

Medicinus ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. 31
Author(s):  
Aziza Ghanie Icksan ◽  
Muhammad Hafiz ◽  
Annisa Dian Harlivasari
Keyword(s):  
Chest Ct ◽  
Rt Pcr ◽  
High Resolution Computed Tomography ◽  
X Ray ◽  
First Case ◽  
Chest X Ray ◽  
Polymerase Chain

<p><strong>Background : </strong>The first case of COVID-19 in Indonesia was recorded in March 2020. Limitation of reverse-transcription polymerase chain reaction (RT-PCR) has put chest CT as an essential complementary tool in the diagnosis and follow up treatment for COVID-19. Literatures strongly suggested that High-Resolution Computed Tomography (HRCT) is essential in diagnosing typical symptoms of COVID-19 at the early phase of disease due to its superior sensitivity  (97%) compared to chest x-ray (CXR).</p><p>The two cases presented in this case study showed the crucial role of chest CT with HRCT to establish the working diagnosis and follow up COVID-19 patients as a complement to RT-PCR, currently deemed a gold standard.<strong></strong></p>

scholarly journals Hlutverk vátryggingafélaga við úrlausn umhverfislegra vandamála

2015 ◽  
Vol 11 (1) ◽  
pp. 87
Author(s):  
Lára Jóhannsdóttir ◽  
Snjólfur Ólafsson ◽  
Brynhildur Davíðsdóttir
Keyword(s):  
Environmental Issues ◽  
Insurance Companies ◽  
Group Differences ◽  
Faroe Islands ◽  
Loss Prevention ◽  
Insurance Sector ◽  
Climate Policies

The purpose of this paper is to discuss the role of insurance companies in solving environmental issues. Environmental issues we now face are many of such magnitude and severity that it is not just up to governments or heavy polluting companies to deal with them, everyone needs to contribute including authorities, institutions, corporations and individuals. Insurance systems differ between countries, but due to the size of the insurance sector and integration with almost every aspect oft society, insurers can be a powerful ally when it comes to implementing environment and climate policies of authorities. The article is based on a Ph.D. research of one of the authors which conducted a multi-case study of 16 Nordic insurance companies in the Åland Islands, Faroe Islands, Iceland, Denmark, Finland, Norway, and Sweden. The companies are divided into two case groups; the Islands group and the Mainland group. Differences in actions/inactions were evident between the case groups, meaning that most of the examples used are from the Mainland group. The environmental and climate change focus areas of the Mainland group are 1) products and services, 2) loss prevention and claim settlement, 3) investments, 4) companies own operation, 5) follow-up, and 6) insurers as a driving force of actions. In case of the Islands companies they mainly focus on loss prevention and few factors that affect their daily activities. Theoretical and practical contribution of the study is to highlight the role and contribution of insurance companies in dealing with environmental issues.

Neonatal Nonketotic Hyperglycinemia: A Case Study and Review of Management for the Advanced Practice Nurse

2013 ◽  
Vol 32 (2) ◽  
pp. 95-103 ◽  
Author(s):  
Joanna L. Mulligan
Keyword(s):  
Autosomal Recessive ◽  
Practice Nurse ◽  
Advanced Practice ◽  
Advanced Practice Nurse ◽  
Neurologic Impairment ◽  
Intractable Seizures ◽  
Glycine Metabolism ◽  
Nonketotic Hyperglycinemia

Nonketotic hyperglycinemia (NKH) is an autosomal recessive inborn error of glycine metabolism. In this article, I will present the case of baby girl S. who presented to the emergency room on Day 4 of life with severe lethargy, seizures, and respiratory depression requiring mechanical ventilation. A diagnosis of NKH was made secondary to elevated plasma and cerebrospinal fluid glycine concentrations. I will review the pathophysiology of NKH, methods of diagnosis, and the differential diagnosis. There are a variety of different pharmacologic and alternative therapies for NKH. Despite these treatments, the prognosis for infants with NKH is poor, with severe neurologic impairment, intractable seizures, and death common before 5 years of age. I will address the role of the advanced practice nurse in caring for an infant with NKH including clinical, educational, and research implications.

scholarly journals Hearing Loss in Mucopolysaccharidoses: Current Knowledge and Future Directions

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 554
Author(s):  
Jeremy Wolfberg ◽  
Keerthana Chintalapati ◽  
Shunji Tomatsu ◽  
Kyoko Nagao
Keyword(s):  
Hearing Loss ◽  
Current Knowledge ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Mixed Hearing Loss ◽  
Hearing Function ◽  
Common Clinical Presentation ◽  
Mps Iva ◽  
Mps Vii ◽  
Mps I

Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by a deficiency of one of the enzymes involved in the degradation of glycosaminoglycans. Hearing loss is a common clinical presentation in MPS. This paper reviews the literature on hearing loss for each of the seven recognized subtypes of MPS. Hearing loss was found to be common in MPS I, II, III, IVA, VI, and VII, and absent from MPS IVB and MPS IX. MPS VI presents primarily with conductive hearing loss, while the other subtypes (MPS I, MPS II, MPS III, MPS IVA, and MPS VII) can present with any type of hearing loss (conductive, sensorineural, or mixed hearing loss). The sensorineural component develops as the disease progresses, but there is no consensus on the etiology of the sensorineural component. Enzyme replacement therapy (ERT) is the most common therapy utilized for MPS, but the effects of ERT on hearing function have been inconclusive. This review highlights a need for more comprehensive and multidisciplinary research on hearing function that includes behavioral testing, objective testing, and temporal bone imaging. This information would allow for better understanding of the progression and etiology of hearing loss. Owing to the prevalence of hearing loss in MPS, early diagnosis of hearing loss and annual comprehensive audiological evaluations are recommended.

scholarly journals Development of Substrate Degradation Enzyme Therapy for Mucopolysaccharidosis IVA Murine Model

2019 ◽  
Vol 20 (17) ◽  
pp. 4139 ◽  
Author(s):  
Kazuki Sawamoto ◽  
Shunji Tomatsu
Keyword(s):  
Positive Impact ◽  
Bone Lesion ◽  
Enzyme Therapy ◽  
Bone Pathology ◽  
Mucopolysaccharidosis Iva ◽  
Enzyme Replacement ◽  
Substrate Degradation ◽  
Mps Iva ◽  
Ph Range ◽  
Optimal Ph

Mucopolysaccharidosis IVA (MPS IVA) is caused by a deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Conventional enzyme replacement therapy (ERT) is approved for MPS IVA. However, the fact that the infused enzyme cannot penetrate avascular lesions in cartilage leads to minimal impact on the bone lesion. Moreover, short half-life, high cost, instability, and narrow optimal pH range remain unmet challenges in ERT. Thermostable keratanase, endo-β-N-acetylglucosaminidase, has a unique character of a wide optimal pH range of pH 5.0–7.0. We hypothesized that this endoglycosidase degrades keratan sulfate (KS) polymer in circulating blood and, therefore, ameliorates the accumulation of KS in multiple tissues. We propose a novel approach, Substrate Degradation Enzyme Therapy (SDET), to treat bone lesion of MPS IVA. We assessed the effect of thermostable keratanase on blood KS level and bone pathology using Galns knock-out MPS IVA mice. After a single administration of 2 U/kg (= 0.2 mg/kg) of the enzyme at 8 weeks of age via intravenous injection, the level of serum KS was significantly decreased to normal range level, and this suppression was maintained for at least 4 weeks. We administered 2 U/kg of the enzyme to MPS IVA mice every fourth week for 12 weeks (total of 3 times) at newborns or 8 weeks of age. After a third injection, serum mono-sulfated KS levels were kept low for 4 weeks, similar to that in control mice, and at 12 weeks, bone pathology was markedly improved when SDET started at newborns, compared with untreated MPS IVA mice. Overall, thermostable keratanase reduces the level of KS in blood and provides a positive impact on cartilage lesions, demonstrating that SDET is a novel therapeutic approach to MPS IVA.

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