Glucocorticoid remediable aldosteronism also describable as aldosterone synthase hyperactivity, is an autosomal dominant disorder in which the increase in aldosterone secretion produced by ACTH is no longer transient. It is a cause of primary hyperaldosteronism. Symptoms and signs
Patients with GRA may be asymptomatic, but the following symptoms can be present:
Fatigue
Headache
High blood pressure
Hypokalemia
Intermittent or temporary paralysis
Muscle spasms
Muscle weakness
Numbness
Polyuria
Polydipsia
Tingling
Hypernatraemia
Metabolic alkalosis

Normal Physiology
Aldosterone synthase is a steroid hydroxylase cytochrome P450 oxidase enzyme involved in the generation of aldosterone. It is localized to the mitochondrial inner membrane. The enzyme has steroid 18-hydroxylase activity to synthesize aldosterone and other steroids. Aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex. Aldosterone synthase normally is not ACTH sensitive, and is only activated by angiotensin II.Aldosterone causes the tubules of the kidneys to retain sodium and water. This increases the volume of fluid in the body and drives up blood pressure.Steroid hormones are synthesized from cholesterol within the adrenal cortex. Aldosterone and corticosterone share the first part of their biosynthetic pathway. The last part is either mediated by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). Aldosterone synthesis is stimulated by several factors:
by increase in the plasma concentration of angiotensin III. by increased plasma angiotensin II, ACTH, or potassium levels. The ACTH stimulation test is sometimes used to stimulate the production of aldosterone along with cortisol to determine if primary or secondary adrenal insufficiency is present. by plasma acidosis. by the stretch receptors located in the atria of the heart.
A meiosis I error can result in isodisomic UPD if the gene loci in question crossed over, for example, a distal isodisomy would be due to duplicated gene loci from the maternal grandmother that crossed over and due to an error during meiosis I, ended up in the same gamete. A meiosis II error can result in heterodisomy UPD if the gene loci crossed over in a similar fashion. Phenotype
Most occurrences of UPD result in no phenotypical anomalies. However, if the UPD-causing event happened during meiosis II, the genotype may include identical copies of the uniparental chromosome (isodisomy), leading to the manifestation of rare recessive disorders. UPD should be suspected in an individual manifesting a recessive disorder where only one parent is a carrier. Uniparental inheritance of imprinted genes can also result in phenotypical anomalies. Although few imprinted genes have been identified, uniparental inheritance of an imprinted gene can result in the loss of gene function, which can lead to delayed development, intellectual disability, or other medical problems. The most well-known conditions include Prader–Willi syndrome and Angelman syndrome. Both of these disorders can be caused by UPD or other errors in imprinting involving genes on the long arm of chromosome 15. Other conditions, such as Beckwith–Wiedemann syndrome, are associated with abnormalities of imprinted genes on the short arm of chromosome 11.