GNE deficiency impairs Myogenesis in C2C12 cells and cannot be rescued by ManNAc supplementation.

GNE myopathy (GNEM) is a late-onset muscle atrophy, caused by mutations in the gene for the key enzyme of sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). With an incidence of one to nine cases per million it is an ultra-rare, so far untreatable, autosomal recessive disease. Several attempts have been made to treat GNEM patients by oral supplementation with sialic acid precursors (e.

Evaluation of -Acetylmannosamine Administration to Restore Sialylation in -Deficient Human Embryonal Kidney Cells.

Background: A key mechanism in the neuromuscular disease GNE myopathy (GNEM) is believed to be that point mutations in the gene impair sialic acid synthesis - maybe due to UDP--acetylglucosamine 2-epimerase/-acetylmannosamine kinase (GNE) activity restrictions - and resulting in muscle tissue loss. -acetylmannosamine (ManNAc) is the first product of the bifunctional GNE enzyme and can therefore be regarded as a precursor of sialic acids. This study investigates whether this is also a suitable substance for restoring the sialic acid content in -deficient cells.

Plasma-derived C1 esterase inhibitor pharmacokinetics and safety in patients with hereditary angioedema.

Background: Over 40 years of use demonstrates that complement 1 esterase inhibitor (C1-INH) concentrate is effective and well tolerated for acute edema attacks and prophylaxis in patients with hereditary angioedema. OCTA-C1-INH is a new stable, virus-inactivated, nanofiltrated concentrate of C1-INH derived from human plasma.

Objective: We investigated the pharmacokinetics and safety profile of new C1-INH in people with hereditary angioedema during an attack-free period.

[Not Available].

Palatal tremor (PT) is a rare cause of objective tinnitus. Symptomatic PT is caused by injuries of the Guillain-Mollaret triangle with contraction of levator veli palatini. Essential PT causes are unknown and is produced by contraction of tensor veli palatini, with pathognomonic audible ear click.

Angioedema With Normal Complement Studies: What Do We Know?

Angioedema is generally readily recognizable clinically and is characterized by localized nonpitting edema involving subcutaneous, submucosal, or deep dermal tissue caused by increased vascular permeability and extravasation of intravascular fluid. It can occur via a variety of mechanisms. A number of clinical conditions (masqueraders) are occasionally mistaken for angioedema.

[Not Available].

Laryngeal dystonia (LD) is a rare neurological disorder emerging in middle-aged persons as a chronic and disabling voice disorder. It is a focal dystonia affecting intrinsic laryngeal muscle control only during speech, resulting in voice breaks, effortful phonation, and strangled voice. Due to lack of awareness and lack of well-defined diagnostic criteria, it can be difficult for patients to be diagnosed and treated.

Glycation Interferes with the Activity of the Bi-Functional UDP--Acetylglucosamine 2-Epimerase/-Acetyl-mannosamine Kinase (GNE).

Mutations in the gene coding for the bi-functional UDP--acetylglucosamine 2-epimerase/-acetylmannosamine kinase (GNE), the key enzyme of the sialic acid biosynthesis, are responsible for autosomal-recessive GNE myopathy (GNEM). GNEM is an adult-onset disease with a yet unknown exact pathophysiology. Since the protein appears to work adequately for a certain period of time even though the mutation is already present, other effects appear to influence the onset and progression of the disease.

Gene Mutations Linked to Hereditary Angioedema in Solitary Angioedema Patients With Normal C1 Inhibitor.

Background: Chronic recurrent angioedema without wheals (CRA) with normal C1 inhibitor (C1-INH) that is unresponsive to antihistamines may involve patients with recurrent angioedema of unknown cause (ie, so-called non-histaminergic idiopathic angioedema) as well as patients with hereditary angioedema with normal C1-INH (HAEnCI) when HAEnCI occurs in only one family member.

Objective: To identify patients with one of type of HAEnCI in a group of patients with CRA with normal C1-INH that was unresponsive to antihistamines.

Methods: A total of 132 patients with CRA and normal C1-INH that was unresponsive to antihistamines underwent mutational and clinical analysis.

Mutant plasminogen in hereditary angioedema is bypassing FXII/kallikrein to generate bradykinin.

Hereditary angioedema (HAE) is characterized by recurrent localized edema in various organs, which can be potentially fatal. There are different types of hereditary angioedema, which include genetic deficiency of C1 inhibitor (C1-INH) and hereditary angioedema with normal C1-INH (HAEnCI). In HAEnCI patients mutations have been identified in the , , , , , and genes.

The associations between stunting and wasting at 12 months of age and developmental milestones delays in a cohort of Cambodian children.

Worldwide, over 250 million children under 5 years do not reach their developmental potential due to several causes, including malnutrition. In Cambodia, the prevalence of stunting and wasting among children remains high. This prospective cohort study aimed to assess acquisition of motor and cognitive developmental milestones in early childhood and their associations with stunting and wasting.

Disturbance of Key Cellular Subproteomes upon Propofol Treatment Is Associated with Increased Permeability of the Blood-Brain Barrier.

Background: Propofol is a short-acting anesthetic, which is often used for induction and maintenance of general anesthesia, sedation for mechanically ventilated adults and procedural sedation. Several side effects of propofol are known and a substantial number of patients suffer from post-operative delirium after propofol application. In this study, we analyzed the effect of propofol on the function and protein expression profile on a proteome-wide scale.

Historical overview and geographical distribution of neglected tropical diseases amenable to preventive chemotherapy in the Republic of the Congo: A systematic review.

Background: Neglected Tropical Diseases amenable to Preventive Chemotherapy (PC-NTDs) affect the poorest populations around the world, especially in Africa. Scientific information on the distribution and level of endemicity of these diseases in the Republic of the Congo (RoC) is scarce in the published literature. We sought to collect all available epidemiological data on PC-NTDs in the RoC to document the historical and current situation and identify challenges in reaching the elimination of NTDs.

The international WAO/EAACI guideline for the management of hereditary angioedema - The 2021 revision and update.

Hereditary Angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process.

Attenuated androgen discontinuation in patients with hereditary angioedema: a commented case series.

Background: Hereditary angioedema (HAE) is characterized by potentially severe and life-threatening attacks of localized swelling. Prophylactic therapies are available, including attenuated androgens. Efficacy of attenuated androgens has not been assessed in large, randomized, placebo-controlled trials and can be associated with frequent, and sometimes severe, side effects.

The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update.

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process.

Glycation Interferes with the Expression of Sialyltransferases in Meningiomas.

Meningiomas are the most common non-malignant intracranial tumors and prefer, like most tumors, anaerobic glycolysis for energy production (Warburg effect). This anaerobic glycolysis leads to an increased synthesis of the metabolite methylglyoxal (MGO) or glyoxal (GO), which is known to react with amino groups of proteins. This reaction is called glycation, thereby building advanced glycation end products (AGEs).

Inheritance Pattern of Hereditary Angioedema Indicates Mutation-Dependent Selective Effects During Early Embryonic Development.

Background: Hereditary angioedema (HAE) may be caused by a genetic deficiency of functional C1 inhibitor (C1-INH) or linked with mutations in the F12, PLG, and other genes in combination with normal C1-INH (HAEnCI). Although the types of hereditary angioedema due to deficiency of functional C1 inhibitor and HAEnCI are autosomal dominant inherited, there is the impression that in the types of HAEnCI more females carry disease-linked mutations.

Objective: The aim of this study was to analyze the passing on of the HAE-specific mutations to the next generations in families with various types of HAE.

Analysis of cold activation of the contact system in hereditary angioedema with normal C1 inhibitor.

Hereditary angioedema (HAE) attacks are caused by excessive activation of the contact system. Understanding how the contact system is activated in HAE, especially in patients with normal C1 inhibitor (HAEnCI), is essential to effectively treat this disease. Contact system activation involves the cleavage of several proteins including Factor XII (FXII), high molecular weight kininogen (HK), prekallikrein, sgp120 (ITIH4) and C1 inhibitor (C1-INH) before the subsequent generation of bradykinin that mediates HAE.

Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report.

Background: Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, potentially life-threatening attacks, resulting in significant physical and emotional burdens for patients and families. To optimize care for patients with HAE, an individualized management plan should be considered in partnership with the physician, requiring comprehensive assessment of the patient's frequency and severity of attacks, disease burden, and therapeutic control. Although several guidelines and consensus papers have been published concerning the diagnosis and treatment of HAE, there has been limited specific clinical guidance on the assessment of disease burden and quality of life (QoL) in this patient population.

The Expanding Spectrum of Mutations in Hereditary Angioedema.

The evolution in the knowledge of rare genetic diseases such as hereditary angioedema (HAE) has increased at a parallel pace with the development of new molecular tools. The deficiency of C1 inhibitor (C1-INH) has been recognized as the main cause of HAE (HAE-C1-INH) since the 1960s, but the discovery of the wide spectrum of mutations affecting the C1-INH gene (SERPING1) was possible only from the late 1980s, when Sanger sequencing became available and more accessible worldwide. Nevertheless, the involvement of other genes in HAE was discovered only in 2006 with the description of mutations in the F12 gene in patients with HAE and normal C1-INH.

Glycation of benign meningioma cells leads to increased invasion.

Meningiomas are the most common non-malignant intracranial tumors. Like most tumors, meningiomas prefer anaerobic glycolysis for energy production (Warburg effect). This leads to an increased synthesis of the metabolite methylglyoxal (MGO).