- A de novo KCNA1 Mutation in a Patient with Tetany and Hypomagnesemia. [Journal Article]
- NNephron 2018 May 23; :1-8
- Mutations in the KCNA1 gene encoding the voltage-gated potassium (K+) channel Kv1.1 have been linked to rare neurological syndromes, episodic ataxia type 1 (EA1) and myokymia. In 2009, a KCNA1 mutati...
Mutations in the KCNA1 gene encoding the voltage-gated potassium (K+) channel Kv1.1 have been linked to rare neurological syndromes, episodic ataxia type 1 (EA1) and myokymia. In 2009, a KCNA1 mutation was identified in a large family with autosomal dominant hypomagnesemia. Despite efforts in establishing a genotype-phenotype correlation for the wide variety of symptoms in EA1, little is known on the serum magnesium (Mg2+) levels in these patients. In the present study, we describe a new de novo KCNA1 mutation in a Polish patient with tetany and hypomagnesemia. Electrophysiological and biochemical analyses were performed to determine the pathogenicity of the mutation. A female patient presented with low serum Mg2+ levels, renal Mg2+ wasting, muscle cramps, and tetanic episodes. Whole exome sequencing identified a p.Leu328Val mutation in KCNA1 encoding the Kv1.1 K+ channel. Electrophysiological examinations demonstrated that the p.Leu328Val mutation caused a dominant-negative loss of function of the encoded Kv1.1 channel. Cell surface biotinylation showed normal plasma membrane expression. Taken together, this is the second report linking KCNA1 with hypomagnesemia, thereby emphasizing the need for further evaluation of the clinical phenotypes observed in patients carrying KCNA1 mutations.
- Mechanisms of metformin action: in and out of the gut. [Editorial]
- JDJ Diabetes Investig 2018 May 19
- One hundred years have passed since guanidine, a precursor compound of biguanides and thus of metformin, was found to have a glucose-lowering effect in live animals1 . In this historical study, C. K....
One hundred years have passed since guanidine, a precursor compound of biguanides and thus of metformin, was found to have a glucose-lowering effect in live animals1 . In this historical study, C. K. Watanabe1 did not set out to identify glucose-lowering agents but rather to understand the mechanism underlying the development of tetany in animals that have undergone parathyroidectomy. Watanabe 1 concluded that guanidine is a pathogenic factor responsible for tetany because its administration in rabbits resulted in "tetany-like" muscle cramps associated with low blood glucose levels. This article is protected by copyright. All rights reserved.
- Prodromal muscle cramps predict rapid motor functional decline in amyotrophic lateral sclerosis. [Letter]
- JNJ Neurol Neurosurg Psychiatry 2018 May 18
- Successful Improvement of Pain Symptomatology in a Suspected Case of Cramp-Fasciculation Syndrome via Interventional Pain Treatment. [Journal Article]
- JPJ Pain Palliat Care Pharmacother 2018 May 18; :1-5
- Peripheral nerve hyperexcitability (PNH) syndromes are a rare set of neuromuscular disorders that include cramp-fasciculation syndrome (CFS) and Isaacs syndrome (IS). Successful treatment of these di...
Peripheral nerve hyperexcitability (PNH) syndromes are a rare set of neuromuscular disorders that include cramp-fasciculation syndrome (CFS) and Isaacs syndrome (IS). Successful treatment of these diseases has been achieved with antiepileptic medications; however, chronic pain symptoms can persist. We provide a case report of a 25-year-old female who has suffered from painful severe muscle spasms and fasciculations since childhood. With CFS as our working diagnosis, a treatment regimen using interventional pain techniques, including sympathetic chain blocks, ketamine infusions, and trigger point injections, resulted in a significant decrease in the patient's chronic pain symptoms. This case offers a novel application of interventional pain procedures and may help further our understanding of PNH syndromes.
- Pilot study of orphenadrine as a novel treatment for muscle cramps in patients with liver cirrhosis. [Journal Article]
- UEUnited European Gastroenterol J 2018; 6(3):422-427
- CONCLUSIONS: Orphenadrine is safe and effective in treatment of muscle cramps in patients with liver cirrhosis.
- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Immunodeficiency results from a failure or absence of elements of the immune system including lymphocytes, phagocytes and complement system. These immunodeficiencies can be either primary such as Bru...
Immunodeficiency results from a failure or absence of elements of the immune system including lymphocytes, phagocytes and complement system. These immunodeficiencies can be either primary such as Bruton’s disease or secondary as the one caused by HIV infection. Primary ImmunodeficiencyB-cell Deficiencies X- linked Agammaglobulinemia (Bruton’s disease): First described by Bruton. X-linked disorder. Found in male babies expressed around 5 to 6 months of age (maternal IgG disappears). In boys, pre-B cells did not differentiate into mature B lymphocytes. There is a mutation in the gene that encodes for a tyrosine kinase protein. Low level of all immunoglobulins (IgG, IgA, IgM, IgD and IgE) is present. Infants with X-linked agammaglobulinemia suffer from recurrent bacterial infections: otitis media, bronchitis, septicemia, pneumonia, and arthritis, and Giardia lamblia causes intestinal malabsorption. Intermittent injections of large amounts of IgG keep the patient alive, but a patient may die at a younger age if infection with antibiotic-resistant bacteria occurs. Selective Immunoglobulin IgA Deficiencies : IgA deficiency is more common than other deficiencies of immunoglobulins. These patients are more prone to recurrent sinus and lung infections. A malfunctioning in heavy-chain gene switching may cause this problem. Treatment should not include gammaglobulin preparations to prevent hypersensitivity reactions. T-cell Immunodeficiencies Congenital thymic Aplasia (DiGeorge Syndrome): Tetany is present. Fungal and viral infections are common. A transplant of the fetal thymus is needed to correct this deficiency. Chronic Mucocutaneous Candidasis: Selective defect in functioning of T-cells. Patient with this disorder usually have a normal T-cell mediated immunity to microorganisms other than Candida. B-cells function is normal. Disorders affect both genders, and it is inherited. Patient in addition to the above will have other disorders like parathyroid deficiencies. Antifungals are useful. Hyper-IgM syndrome: This disorder is characterized by bacterial infections including pneumonia, meningitis, otitis, among others that start in early childhood. High levels of IgM. Other immunoglobulins are defective. Lymphocytes are normal in numbers. The gene encoding the CD40 ligand on T lymphocytes is faulty. B and T lymphocyte cooperation in the immune response is compromised. The failure to interact with CD40 results in an inability of the B cell to switch from the production of IgM to the other classes of antibodies. Immunoglobulin therapy is recommended. Interleukin-12 receptor deficiency: Mycobacterial infections are frequent due to the lack of the interleukin-12 receptor. Treatment involves selective antimicrobials. T-cell and B-cell Deficiencies Severe combined immunodeficiency disease (SCID): There is a failure of early stem cells to differentiate into T and B lymphocytes. Deficiency of the interleukin-2 receptor is the most prevalent. Other problems are due to defective genes encoding ZAP-70, Janus kinase 3 and the genes involved in the DNA recombination of immune cells receptors: RAG1 and RAG2. Clinically characterized by a variety of infections, including those caused by opportunistic pathogens. Selective antibiotics, antivirals, and antifungals are available after the pathogen identification. Immunosuppressive therapy is not needed after allograft transplantation. Wiskott-Aldrich syndrome: This syndrome is associated with normal T-cell numbers with reduced functions, which get progressively worse. IgM concentrations are reduced, but IgG levels are normal. Both IgA and IgE levels are elevated. These patients have a defective WASP which is involved in actin filament assembly. Immunodeficiency with ataxia-telangiectasia: This is a deficiency of T-cells associated with a lack of coordination of movement (ataxia) and dilation of small blood vessels of the facial area (telangiectasis). T-cells and their functions are diminished to various degrees. B-cell numbers and IgM concentrations are normal to low. IgG is often reduced, and IgA is considerably reduced. There is a high incidence of malignancy, especially leukemias, in these patients. MHC deficiency (Bare leukocyte syndrome): This subjects have have fewer CD4+ or CD8+ T lymphocytes that predispose to these individuals to be prone to recurrent infections. Antibody production is affected and predispose to bacteremia. Complement Deficiencies Hereditary angioedema : This disease has an autosomal dominant genetic pattern. Caused by C1 inhibitor deficiency. Clinically characterized by generalized edema including the one leading to acute suffocation. Therapy with oxymetholone and danazol can be helpful in correcting the defect. Recurrent infections: Frequent infections by extracellular bacteria may be caused by C3 deficiency. C5 deficiency predisposes to viral infections. Patients with deficiency of the membrane attack complex (MAC) are particularly susceptible to bacteremia caused by Neisseria species. Autoimmune diseases This are caused by C2 and C4 deficiencies and mimic systemic lupus erythematosus. Phagocyte Deficiencies Chronic granulomatous disease (CGD): It is mostly an X-linked disorder. It is clinically characterized by a defective NADPH that interferes with the intracellular ability of neutrophils to kill engulfed bacteria species. NAPDH oxidase is required for the generation of peroxidase and superoxides that will kill the organisms. The intracellular survival of the organisms leads to the formation of a granuloma, an organized structure consisting of mononuclear cells. These granulomas can become large enough to obstruct the stomach, esophagus, or bladder. Patients with this disease are very susceptible to opportunistic infection by certain bacteria and fungi especially with Serratia and Burkholderia. Nitroblue tetrazolium (NBT) dye reduction test confirms the diagnosis of CGD and the dichlorofluorescein (DCF) test is also useful. Aggressive therapy with wide spectrum antibiotics and antifungal agents is required. Leukocyte adhesion deficiency syndrome: Characterized by pyogenic infections including pneumonia and otitis. It is an autosomal recessive disease, and the faulty gene encodes for an integrin. There is an impaired adhesion and defective phagocytosis of bacteria. Treatment involves the use of selective antibiotics. Secondary Immunodeficiency Use of Drugs (Steroids) : Administration of steroids has direct effects on immune cell traffic and functions. T cells are more affected than B cells. Cytokine synthesis is inhibited. Nutrient Deficiencies : They are associated with impaired immune system. Affects cell-mediated immunity, antibody production, phagocyte function, complement system and cytokine synthesis. Aggravated by infections. Multiple enzymes with important roles require zinc, iron and other micronutrients. Obesity : It may cause impaired immune responses. There is altered NK function. Cytotoxicity is compromised and the ability of phagocytes to kill microorganisms. Acquired Immune Deficiency Syndrome (AIDS) : Caused by human immunodeficiency virus (HIV), which is a retrovirus transmitted sexually, perinatally or blood products. Immune dysfunction results from the direct effects of HIV and impairment of CD4 T cells. HIV proteins may act as superantigens. There is decreased responses to antigens and mitogens. Interleukin-2 and other cytokines are decreased. Infected cells may be killed by HIV-1 specific CD8+ T cells. In HIV-1 infection neutralizing antibodies appear to be ineffective in controlling viral replication and infection.
- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- The cramp is caused by a continuous, involuntary, painful, and localized contraction of a muscle or simply some muscle bundles. Generally, the cramp can last from minutes to a few seconds for idiopat...
The cramp is caused by a continuous, involuntary, painful, and localized contraction of a muscle or simply some muscle bundles. Generally, the cramp can last from minutes to a few seconds for idiopathic or known causes with healthy subjects or in the presence of diseases. Palpating the muscle area of the cramp will present a knot. Although a frequent event, it is not always simple to find an explanation for this phenomenon. Possible causes depend on the physiological or pathological situation in which the cramps appear. It is important to note that a painful contraction that is limited to a specific area does not mean that the cause of the onset of the cramp is necessarily local. A cramp is almost never a local effect but involves the whole body system: somatic and emotional.
- Identification and Functional Characterization of a Novel Mutation in the Human Calcium-Sensing Receptor That Co-Segregates With Autosomal-Dominant Hypocalcemia. [Journal Article]
- FEFront Endocrinol (Lausanne) 2018; 9:200
- The human calcium-sensing receptor (CASR) is the key controller of extracellular Cao2+ homeostasis, and different mutations in the CASR gene have been linked to different calcium diseases, such as fa...
The human calcium-sensing receptor (CASR) is the key controller of extracellular Cao2+ homeostasis, and different mutations in the CASR gene have been linked to different calcium diseases, such as familial hypocalciuric hypercalcemia, severe hyperparathyroidism, autosomal-dominant hypocalcemia (ADH), and Bartter's syndrome type V. In this study, two generations of a family with biochemically and clinically confirmed ADH who suffered severe muscle pain, arthralgia, tetany, abdominal pain, and fatigue were evaluated for mutations in the CASR gene. The study comprises genotyping of all family members, functional characterization of a potential mutant receptor by in vitro analysis related to the wild-type receptor to reveal an association between the genotype and phenotype in the affected family members. The in vitro analysis of functional characteristics includes measurements of inositol trisphosphate accumulation, Ca2+ mobilization in response to [Ca2+]o-stimulation and receptor expression. The results reveal a significant leftward shift of inositol trisphosphate accumulation as a result of the "gain-of-function" mutant receptor and surprisingly a normalization of the response in (Ca2+)i release in the downstream pathway and additionally the maximal response of (Ca2+)i release was significantly decreased compared to the wild type. However, no gross differences were seen in D126V and the D126V/WT CASR dimeric >250 kDa band expression compared to the WT receptor, however, the D126V and D126V/WT CASR immature ~140 kDa species appear to have reduced expression compared to the WT receptor. In conclusion, in this study, a family with a clinical diagnosis of ADH in two generations was evaluated to identify a mutation in the CASR gene and reveal an association between genotype and phenotype in the affected family members. The clinical condition was caused by a novel, activating, missense mutation (D126V) in the CASR gene and the in vitro functional characteristics of the mutation co-segregated with their individual phenotype.
- Abdominal skeletal muscle activity precedes spontaneous menstrual cramping pain in primary dysmenorrhea. [Journal Article]
- AJAm J Obstet Gynecol 2018 May 04
- CONCLUSIONS: Abdominal muscle activity may contribute to cramping pain in primary dysmenorrhea, but is resolvable with naproxen. Dysmenorrheic patients without cramp-associated abdominal muscle activity exhibit widespread pain sensitivity (lower pressure pain thresholds) and are more likely to also have a chronic pain diagnosis, suggesting their cramps are linked to changes in central pain processes. This preliminary study suggests new tools to phenotype menstrual pain and supports the hypothesis that multiple distinct mechanisms may contribute to dysmenorrhea.
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- Symmetrical and bilateral basal ganglia calcification. Case series and literature review. [Journal Article]
- GMGac Med Mex 2018; 154(2):258-262
- CONCLUSIONS: Ganglia calcification can be associated with age-related neurodegenerative changes, but it can be an initial manifestation of a variety of systemic pathologies, including disorders of the calcium metabolism, intoxication by different agents, and autoimmune and genetic diseases. Correlation of typical imaging findings with clinical manifestations and laboratory results should be established to reach a definitive judgment.