Liddles syndrome

Data in part from Ackerman NJ, Clapham DE Ion channels— basic science and clinical disease. N Engl J Med 1997,-336 1575. Other channelopathies include the long QT syndrome (MIM 192500) pseudoaldosteronism (Liddle syndrome, MIM 177200) persistent hyperinsulinemic hypoglycemia of infancy (MIM 601820) hereditary X-linked recessive type II nephrolithiasis of infancy (Dent syndrome, MIM 300009) and generalized myotonia, recessive (Becker disease, MIM 255700). The term "myotonia" signifies any condition in which muscles do not relax after contraction. 

Andreoli TE Ion transport disorders introductory comments. Am J Med 1998 104 85. (First of a series of articles on ion transport disorders published between January and August, 1998. Topics covered were structure and function of ion channels, arrhythmias and antiarrhythmic drugs, Liddle syndrome, cholera, malignant hyperthermia, cystic fibrosis, the periodic paralyses and Bartter syndrome, and Gittelman syndrome.)... 

The major disease clearly linked with disordered sodium homeostasis, among other diseases, is hypertension, and this is observed in very small populations with genetic defects including glucocorticoid-responsive aldosteronism, Liddle syndrome, and apparent mineralocorticoid excess (AME) (Anke 2002). Cystic fibrosis is another genetically determined defect in the chloride channels. This leads to the secretion of sweat with high NaCl concen-... 

Familial hypomagnesem ia-hypercalciuria Dent disease Liddle syndrome... 

Liddle s syndrome is an autosomal dominant disorder that is caused by persistent hyperactivity of the epithelial Na channel. Its symptoms mimic aldosterone excess, but plasma aldosterone levels are actually reduced (pseudoaldosteronism). The disease is characterized by early onset arterial hypertension, hypokalemia, and metabolic alkalosis. 

Disease-causing mutations are found in the cytoplasmic regulatory region of the (3 and y subunits of the epithelial sodium channel (ENaC) genes. In general, patients with Liddle s syndrome can be treated successfully with the ENaC inhibitor amiloride. 

Example, Bartter s or Gitelman s syndrome, Cushing s syndrome, hyperaldosteronism (1° or 2°), and Liddle s syndrome... 

Staub, O., S. Dho, P. Henry, J. Correa, T. Ishikawa, J. McGlade, and D. Rotin. WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle s syndrome. Embo J. 15 2371-80.1996. 

Corvol, P. (1995). Liddle s syndrome heritable human hypertension caused by mutations in the Beta subunit of the epithelial sodium channel. J. Endocrinol. Invest., 18(7), 592-594. 

Pseudoaldosteronism (Liddle s syndrome) Na+ channel defect SCNN1BSCNN1G 16pl3-pl2 16pl3-pl2 600760 600761(177200)... 

Liddle s syndrome is an autosomal dominant form of hypertension. It is a disorder of the renal epithelial sodium channel, which has three subunits, a, j, and y, and mutations within the first two are associated with increased sodium channel activity [7, 36]. This causes excessive sodium absorption in the distal nephron of the kidney. It gives rise to hypoglycemia, low -renin, and low aldosterone. 

Botero-Velez M, Curtis JJ, Warnock DG (1994) Liddle s syndrome revisited - a disorder of sodium reabsorption in the distal tubule. N Engl J Med 330 178-181... 

Schizophrenia is a complex neuropsychiatric disorder with a prevalence of nearly 1% of the world population. Clinically, schizophrenia is characterized by chronic psychotic symptoms and psychosocial impairment. At least two core syndromes of schizophrenia, the positive and the negative, are recognized (Liddle, 1987). Those in whom positive symptoms predominate have hallucinations, delusions, and paranoid ideation. Those with negative symptoms have apathy and anledonia. Besides impairment in the cognitive domain, individuals with schizophrenia show a deficit in emotion processing, as indicated by a markedly reduced ability to perceive, process, and express facial emotions (Aleman et al., 1999). 

SCNNIB/G 16pl2.2-pl2.1 ENaC Liddle s syndrome D Gain... 

Liddle, P. F., T. R. E. Barnes, D. Morris, and S. Haque. 1989. Three syndromes in chronic schizophrenia. British Journal of Psychiatry 155 (Suppl 7)119-22. 

Other unusual conditions that suggest aldosterone excess or deficiency but are not connected to the renin-angiotensin-aldosterone system include Liddle s syndrome (pseudo hyper aldosteronism),which resembles primary aldosteronism clinically, but aldosterone production is low and hypertension is absent and Barttefs syndrome,which involves a prostaglandin-mediated renal potassium wasting and renal chloride handling defect, in which both aldosterone concentrations and renin activities are elevated. In renal tubular acidosis and pseudohypoaldosteronism, the clinical picture of hypoaldosteronism is seen concurrent with greater-than-normal concentrations of aldosterone. 

Excess mineralocorticoid activity Hyperaldosteronism Cushing s syndrome Bartter s syndrome Gitelman s syndrome Excessive black licorice intake Profound potassium depletion Magnesium deficiency Liddle s syndrome Unclassified Alkali administration Milk-alkali syndrome... 

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