Signs Of Hyponatremia Research Articles

In silico structural, functional and pathogenicity evaluation of a novel mutation: An overview of HSD3B2 gene mutations

Mutations of 3 beta hydroxysteroid dehydrogenase type II (HSD3B2) gene result in different clinical consequences. We explain a patient who demonstrated a salt wasting form of 3βHSD deficiency in infancy. Signs of hyponatremia and hyperkalemia were recognized in the infant with ambiguous genitalia and perineal hypospadias. The 46,XY male was genotyped by direct sequencing of HSD3B2 gene. Steroid profiles showed elevated concentration of 17 hydroxyprogesterone, and decrease in concentration of cortisol, and testosterone. Dehydroepiandrotone (DHEA) to androstenedione ratio had 6 fold increases. Direct sequencing of the patient revealed homozygous missense A82P mutation in exon 3. This mutation was confirmed by segregation analysis of the parents. Bioinformatic tools were used for in silico structural and functional analyses. Also, the pathological effect of the mutation was validated by different software. Alanine is a conserved amino acid in the membrane binding domain of the enzyme and proline substitution was predicted to destabilize the protein. This report may highlight the importance of the screening programs of the disorder in Iran.

Do salt cravings in children with autistic disorders reveal low blood sodium depleting brain taurine and glutamine?

Because boys are four times more likely than girls to develop autism, the role of male hormones (androgens) has received considerable scrutiny. Some researchers implicate arginine vasopressin, an androgen-dependent hormone from the pituitary gland that elicits male behavior. Elevated vasopressin is also the most common cause of low blood sodium (hyponatremia) – most serious in the brains of children. Hyponatremia causes astrocytes to swell, then release the amino acids taurine and glutamine and their water to compensate. Taurine – the brain osmolyte/inhibitory neurotransmitter that suppresses vasopressin – was the amino acid most wasted or depleted in urine of autistic children. Glutamine is a critical metabolic fuel in brain neurons, astrocytes, endothelial cells, and the intestines, especially during hypoglycemia. Because glutamine is not thought to cross the blood–brain barrier significantly, the implications of low blood glutamine in these children are not recognized. Yet children with high brain glutamine from urea cycle disorders are rarely diagnosed with autistic disorders. Other common events in autistic children that release vasopressin are gastrointestinal inflammation, hypoglycemia, and stress. Signs of hyponatremia in these children are salt cravings reported online and anecdotally, deep yellow urine revealing concentration, and relief of autistic behavior by fluid/salt diets. Several interventions offer promise: (a) taurine to suppress vasopressin and replenish astrocytes; (b) glutamine as fuel for intestines and brain; (c) arginine to spare glutamine, detoxify ammonia, and increase brain blood flow; and (d) oral rehydration salts to compensate dilutional hyponatremia. This hypothesis appears eminently testable: Does your child crave salt? Is his urine deep yellow?

Hyponatremia and Arginine Vasopressin Dysregulation: Mechanisms, Clinical Consequences, and Management

Hyponatremia, the most common electrolyte disorder, occurs frequently in older people and in hospitalized patients. Physiological changes of aging that interact with diseases and drugs commonly present in older people put this population at greater risk for hyponatremia. It can accompany central nervous system disorders, pulmonary and renal disease, cancer, congestive heart failure, and liver cirrhosis, as well as many commonly used drugs. Delayed recognition can lead to symptomatic hyponatremia with consequent cerebral edema and possibly irreversible neurological damage. Symptoms and signs of hyponatremia may be subtle or not attributed to hyponatremia. Most cases are of the euvolemic type, in which extracellular fluid volume is normal and is often due to the syndrome of inappropriate secretion of antidiuretic hormone. Hyponatremia can also occur in association with hypervolemia or hypovolemia. Common to all of these circumstances is increased secretion of arginine vasopressin (AVP). Understanding of the pathophysiological basis of hyponatremia and of brain compensatory mechanisms is critical to safe treatment. Fluid restriction or infusion of hypertonic saline can improve symptoms and normalize serum sodium levels but does not address excess AVP, which in most cases is the underlying cause of the disorder. A major new approach to treatment of hyponatremia is the development of aquaretics: AVP-receptor antagonists that provide a targeted therapeutic approach to correcting the many kinds of hyponatremia caused by excess AVP levels.