scholarly journals 5th Rare Disease South Eastern Europe (SEE) Meeting, Skopje, Macedonia (November 15th, 2016)

PRILOZI ◽  
2017 ◽  
Vol 38 (1) ◽  
pp. 119-123
Author(s):  
Zoran Gucev ◽  
Velibor Tasic ◽  
Momir Polenakovic
Keyword(s):  
Mitochondrial Diseases ◽  
Renal Stones ◽  
Glycogen Storage ◽  
Diagnosis And Treatment ◽  
Renal Diseases ◽  
Enzyme Replacement ◽  
Replacement Treatment ◽  
Glycogen Storage Diseases ◽  
Gene Treatment ◽  
Special Lecture

Abstract The fifth SEE meeting on rare diseases (RDs) was held in Macedonian Academy of Sciences and Arts (MASA) the November 11th, 2016. Several lectures dealt with mucopolysaccharidosis, glycogen storage diseases and the possibilities for their diagnosis and treatment. Enzyme replacement treatment (ERT), its availability, effects (or the lack of it) on the brain, and further prospects of eventual gene treatment were comprehensively exposed and discussed. Special accent was on Gaucher, Morquio IVA, Hunter and the audience was given new knowledge on the complexities of diagnosis and treatment. A block of lectures on rare renal diseases was also impressive. From renal stones, their molecular and genetic mechanisms to different forms of CAKUT the use of NGS and other molecular methods in diagnosis of RDs. Mitochondrial diseases, the novelties and importance of early discovery were comprehensively exposed. Special lecture was given on the complement system. Endocrine disruptors, microprolactinomas were also the topic of the meeting. A rather reach session of posters was also presented.

scholarly journals The 6th Rare Disease South Eastern Europe (See) Meeting, Skopje, Macedonia (November 11th, 2017)

PRILOZI ◽  
2017 ◽  
Vol 38 (3) ◽  
pp. 163-168
Author(s):  
Zoran Gucev ◽  
Velibor Tasic ◽  
Momir Polenakovic
Keyword(s):  
Mitochondrial Diseases ◽  
Glycogen Storage ◽  
Hypophosphatemic Rickets ◽  
Renal Diseases ◽  
Enzyme Replacement ◽  
Glycogen Storage Diseases ◽  
Gene Treatment ◽  
Number Of Patients ◽  
Genetic Mechanisms ◽  
South Eastern Europe

Abstract The sixth SEE meeting on rare diseases (RDs) was held in MASA the November 10th, 2017. A block of lectures on rare renal diseases started the meeting: nephrotic syndrome, Alport syndrome, atypical HUS, hypophosphatemic rickets, CAKUT were presented in all complexities. Their molecular and genetic mechanisms were discussed. The discovery of a dozen of newly genes in CAKUT, congenital overgrowth, spodilocostal dysplasia, precocious puberty has been done with collaboration of Macedonian and foreign researchers. NGS and other molecular methods in diagnosis of RDs have been presented by several presenters. The mitochondrial diseases, the novelties and importance of early discovery were comprehensively presented and discussed. The genetics and treatment of persistent neonatal hypoglcaemia were of special interest. Dysmorphic syndromes (Klippel Feil) were also presented. A session of oral electronic posters was reach and inspiring. Several lectures dealt with mucopolisaccaridoses, glycogen storage diseases and the possibilities for their diagnosis and treatment. Enzyme replacement treatement (ERT), its availability, effects (or the lack of it on the brain), intratecal ERT administration and further prospects of eventual gene treatment were comprehensively exposed and discussed. The main purposes of this traditional meeting are hopefully fulfilled: increased number of patients with RDs treated and cutting edge presentations got.

scholarly journals Renal Calculi as Initial Presenting Symptom of Glycogen Storage Disease (Type 1 A) in Early Infancy

2020 ◽  
Vol 10 (01) ◽  
pp. e45-e47
Author(s):  
Nida Mirza ◽  
Smita Malhotra ◽  
Anupam Sibal
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Case Reports ◽  
Glycogen Synthesis ◽  
Renal Stones ◽  
Renal Calculi ◽  
Glycogen Storage ◽  
Storage Diseases ◽  
Glycogen Storage Diseases

AbstractGlycogen storage diseases are a group of heterogeneous metabolic disorders that result from a defect in enzymatic pathway of either glycogen synthesis or glycogen degradation. Here we are reporting a case of glycogen storage diseases type 1 with renal stone as initial manifestation of disease at 2 months of age. There were case reports of recurrent renal calculi in older age group with this disease and considered to be arisen due to metabolic derangements. Although the exact mechanism of renal stones in glycogen storage disease is not clear, in this unique case occurrence of renal stones at 2 months of age suggests that the pathogenesis of renal calculi is probably multifactorial or a part of disease.

scholarly journals Hypertrophic Cardiomyopathy in Children: Pathophysiology, Diagnosis, and Treatment of Non-sarcomeric Causes

2021 ◽  
Vol 9 ◽  
Author(s):  
Emanuele Monda ◽  
Marta Rubino ◽  
Michele Lioncino ◽  
Francesco Di Fraia ◽  
Roberta Pacileo ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Neuromuscular Diseases ◽  
Glycogen Storage ◽  
Left Ventricular ◽  
Diagnosis And Treatment ◽  
Acid Oxidation ◽  
Lysosomal Storage ◽  
Mortality And Morbidity ◽  
Storage Diseases ◽  
Glycogen Storage Diseases

Hypertrophic cardiomyopathy (HCM) is a myocardial disease characterized by left ventricular hypertrophy not solely explained by abnormal loading conditions. Despite its rare prevalence in pediatric age, HCM carries a relevant risk of mortality and morbidity in both infants and children. Pediatric HCM is a large heterogeneous group of disorders. Other than mutations in sarcomeric genes, which represent the most important cause of HCM in adults, childhood HCM includes a high prevalence of non-sarcomeric causes, including inherited errors of metabolism (i.e., glycogen storage diseases, lysosomal storage diseases, and fatty acid oxidation disorders), malformation syndromes, neuromuscular diseases, and mitochondrial disease, which globally represent up to 35% of children with HCM. The age of presentation and the underlying etiology significantly impact the prognosis of children with HCM. Moreover, in recent years, different targeted approaches for non-sarcomeric etiologies of HCM have emerged. Therefore, the etiological diagnosis is a fundamental step in designing specific management and therapy in these subjects. The present review aims to provide an overview of the non-sarcomeric causes of HCM in children, focusing on the pathophysiology, clinical features, diagnosis, and treatment of these rare disorders.

The heart in inherited metabolic disorders: lysosomal and glycogen storage diseases

ESC CardioMed ◽  
2018 ◽  
pp. 1540-1545
Author(s):  
Ales Linhart
Keyword(s):  
Glycogen Storage ◽  
Lysosomal Storage ◽  
Acid Hydrolases ◽  
Cardiac Damage ◽  
Irreversible Damage ◽  
Storage Diseases ◽  
Activator Proteins ◽  
Enzyme Replacement ◽  
Glycogen Storage Diseases ◽  
Myocardial Involvement

Lysosomal storage diseases (LSDs) represent a large and heterogeneous group of rare inherited disorders caused by a defective function of one of the lysosomal acid hydrolases, their activator proteins, or proteins necessary for intracellular trafficking. The diseases are characterized by an accumulation of macromolecules representing substrates for defective enzymes. Most diseases affect multiple organs causing neurological, musculoskeletal, gastrointestinal and hepatic involvement, renal, and cardiac damage. Several diseases cause myocardial involvement manifesting as hypertrophic or less frequently dilated cardiomyopathy, arrhythmias (conduction abnormalities, bradycardia, and ventricular arrhythmias), valvular lesions, and coronary involvement. Several lysosomal diseases are now treatable by enzyme replacement therapy or by chaperones. The group of glycogen storage diseases largely overlaps with LSDs. In addition to LSDs causing glycogen storage and myocardial involvement (Pompe and Danon diseases), cytoplasmic glycogen metabolism is disturbed in PRKAG2 autosomal dominant cardiomyopathy. The recognition of specific causes of myocardial involvement may allow a timely treatment by specific therapies preventing irreversible damage.

scholarly journals Hypertrophic Cardiomyopathy and Primary Restrictive Cardiomyopathy: Similarities, Differences and Phenocopies

2021 ◽  
Vol 10 (9) ◽  
pp. 1954
Author(s):  
Riccardo Vio ◽  
Annalisa Angelini ◽  
Cristina Basso ◽  
Alberto Cipriani ◽  
Alessandro Zorzi ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Restrictive Cardiomyopathy ◽  
Glycogen Storage ◽  
Left Ventricular ◽  
Pathophysiological Mechanism ◽  
Storage Diseases ◽  
Glycogen Storage Diseases ◽  
Similar Genetic Background ◽  
Ventricular Wall Thickness ◽  
And Storage

Hypertrophic cardiomyopathy (HCM) and primary restrictive cardiomyopathy (RCM) have a similar genetic background as they are both caused mainly by variants in sarcomeric genes. These “sarcomeric cardiomyopathies” also share diastolic dysfunction as the prevalent pathophysiological mechanism. Starting from the observation that patients with HCM and primary RCM may coexist in the same family, a characteristic pathophysiological profile of HCM with restrictive physiology has been recently described and supports the hypothesis that familiar forms of primary RCM may represent a part of the phenotypic spectrum of HCM rather than a different genetic cardiomyopathy. To further complicate this scenario some infiltrative (amyloidosis) and storage diseases (Fabry disease and glycogen storage diseases) may show either a hypertrophic or restrictive phenotype according to left ventricular wall thickness and filling pattern. Establishing a correct etiological diagnosis among HCM, primary RCM, and hypertrophic or restrictive phenocopies is of paramount importance for cascade family screening and therapy.

scholarly journals Clinical and genetic spectrum of glycogen storage disease in Iranian population using targeted gene sequencing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zahra Beyzaei ◽  
Fatih Ezgu ◽  
Bita Geramizadeh ◽  
Mohammad Hadi Imanieh ◽  
Mahmood Haghighat ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Molecular Genetic ◽  
Gene Sequencing ◽  
Glycogen Storage ◽  
Loss Of Function ◽  
Retrospective Case ◽  
Complex Disorders ◽  
Glycogen Storage Diseases ◽  
Targeted Gene Sequencing ◽  
Retrospective Case Study

AbstractGlycogen storage diseases (GSDs) are known as complex disorders with overlapping manifestations. These features also preclude a specific clinical diagnosis, requiring more accurate paraclinical tests. To evaluate the patients with particular diagnosis features characterizing GSD, an observational retrospective case study was designed by performing a targeted gene sequencing (TGS) for accurate subtyping. A total of the 15 pediatric patients were admitted to our hospital and referred for molecular genetic testing using TGS. Eight genes namely SLC37A4, AGL, GBE1, PYGL, PHKB, PGAM2, and PRKAG2 were detected to be responsible for the onset of the clinical symptoms. A total number of 15 variants were identified i.e. mostly loss-of-function (LoF) variants, of which 10 variants were novel. Finally, diagnosis of GSD types Ib, III, IV, VI, IXb, IXc, X, and GSD of the heart, lethal congenital was made in 13 out of the 14 patients. Notably, GSD-IX and GSD of the heart-lethal congenital (i.e. PRKAG2 deficiency) patients have been reported in Iran for the first time which shown the development of liver cirrhosis with novel variants. These results showed that TGS, in combination with clinical, biochemical, and pathological hallmarks, could provide accurate and high-throughput results for diagnosing and sub-typing GSD and related diseases.

scholarly journals Targeted Therapies for Metabolic Myopathies Related to Glycogen Storage and Lipid Metabolism: a Systematic Review and Steps Towards a ‘Treatabolome’

2021 ◽  
pp. 1-18
Author(s):  
A. Manta ◽  
S. Spendiff ◽  
H. Lochmüller ◽  
R. Thompson
Keyword(s):  
Systematic Review ◽  
Lipid Metabolism ◽  
Genetic Defect ◽  
Genetic Mutation ◽  
Glycogen Storage ◽  
Carnitine Deficiency ◽  
Exercise Intolerance ◽  
Enzyme Replacement ◽  
Metabolic Myopathies ◽  
Published Evidence

Background: Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intolerance, myalgia and progressive muscle weakness. Effective treatments for some of these diseases are available, but while our understanding of the pathogenesis of metabolic myopathies related to glycogen storage, lipid metabolism and β-oxidation is well established, evidence linking treatments with the precise causative genetic defect is lacking. Objective: The objective of this study was to collate all published evidence on pharmacological therapies for the aforementioned metabolic myopathies and link this to the genetic mutation in a format amenable to databasing for further computational use in line with the principles of the “treatabolome” project. Methods: A systematic literature review was conducted to retrieve all levels of evidence examining the therapeutic efficacy of pharmacological treatments on metabolic myopathies related to glycogen storage and lipid metabolism. A key inclusion criterion was the availability of the genetic variant of the treated patients in order to link treatment outcome with the genetic defect. Results: Of the 1,085 articles initially identified, 268 full-text articles were assessed for eligibility, of which 87 were carried over into the final data extraction. The most studied metabolic myopathies were Pompe disease (45 articles), multiple acyl-CoA dehydrogenase deficiency related to mutations in the ETFDH gene (15 articles) and systemic primary carnitine deficiency (8 articles). The most studied therapeutic management strategies for these diseases were enzyme replacement therapy, riboflavin, and carnitine supplementation, respectively. Conclusions: This systematic review provides evidence for treatments of metabolic myopathies linked with the genetic defect in a computationally accessible format suitable for databasing in the treatabolome system, which will enable clinicians to acquire evidence on appropriate therapeutic options for their patient at the time of diagnosis.

scholarly journals mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jingsong Cao ◽  
Minjung Choi ◽  
Eleonora Guadagnin ◽  
Maud Soty ◽  
Marine Silva ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Murine Model ◽  
Storage Disease ◽  
Liver Tumors ◽  
Glycogen Storage ◽  
Human Condition ◽  
Efficacy And Safety ◽  
Current Standard ◽  
Enzyme Replacement ◽  
Life Threatening

AbstractGlycogen Storage Disease 1a (GSD1a) is a rare, inherited metabolic disorder caused by deficiency of glucose 6-phosphatase (G6Pase-α). G6Pase-α is critical for maintaining interprandial euglycemia. GSD1a patients exhibit life-threatening hypoglycemia and long-term liver complications including hepatocellular adenomas (HCAs) and carcinomas (HCCs). There is no treatment for GSD1a and the current standard-of-care for managing hypoglycemia (Glycosade®/modified cornstarch) fails to prevent HCA/HCC risk. Therapeutic modalities such as enzyme replacement therapy and gene therapy are not ideal options for patients due to challenges in drug-delivery, efficacy, and safety. To develop a new treatment for GSD1a capable of addressing both the life-threatening hypoglycemia and HCA/HCC risk, we encapsulated engineered mRNAs encoding human G6Pase-α in lipid nanoparticles. We demonstrate the efficacy and safety of our approach in a preclinical murine model that phenotypically resembles the human condition, thus presenting a potential therapy that could have a significant therapeutic impact on the treatment of GSD1a.

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