Liddle Syndrome

What is Liddle Syndrome?

Liddle syndrome is an unusual genetic disorder that is also known as pseudohyperaldosteronism, and is associated with some impairment in the epithelial sodium channel (ENaC) system or with an amiloride sensitive sodium channel, which are collecting tubule sodium channels of the kidneys.

There will be an excessive amount of reabsorption for sodium in the body and with a loss of potassium coming from the kidney tubules. This health problem is characterized by a severe type of hypertension that is mostly observed in an earlier stage of life during the childhood period, though the diagnosis for some are confirmed upon reaching adulthood.

This is also linked among patients who present with low levels of potassium, renin, and aldosterone in the blood plasma content.

Symptoms of Liddle Syndrome

Children who have Liddle syndrome are mostly not presenting themselves to have the clinical manifestations of this condition.

The most common clinical symptom is an early onset of severe hypertension during childhood that is usually assessed when obtaining for a routine physical examination. Physicians give the child a special consideration to have this rare problem after it gives no response to treatment started to lower the blood pressure levels.

Other nonspecific symptoms among adult patients include:

• Signs of Hypokalemia – These are pain felt in the muscles, fatigability, muscle weakness, palpitations of the heart, shortness of breath, exercise intolerance, abdominal distention or constipation. The sign of a long-standing hypertension can become asymptomatic in time.
• Metabolic alkalosis – This is the result of the shortage of potassium supply in the body which at the same time can raise the pH level of the blood.

Liddle syndrome and autosomal recessive pseudohypoaldosteronism type 1 are both rare genetic problems linked with a malfunction of the ENaC. There is an increased level of ENaC function in Liddle’s Syndrome.

The ENaC function is seen to be decreasing in an autosomal recessive pseudohypoaldosteronism type 1, that ends up with a resistance to aldosterone.

Causes of Liddle Syndrome

Liddle syndrome is basically caused by a problem in the regulation of the ENaC as revealed in the genetic mutations through some studies involving the beta coding SCNN1B (Amiloride-sensitive sodium channel beta) or gamma coding SCNN1G (Amiloride-sensitive sodium channel gamma) subunits located in the chromosome 16p13-p12, where proline-rich regions are being deleted.

As this occurs, the E3 ligase Nedd4 (Neural precursor cell expressed developmentally down-regulated protein 4) is no longer recognized by the channels specifically found in the kidneys, the lungs and sweat glands.

The mutations affect the subunit proteins not to be degraded, giving way to more ENaC channels to stay in the surface of the cells. The increase of ENaC channels present leads to an increase in the reabsorption of the element sodium, and then followed by more water reabsorption, obtaining an end result of hypertension.

The reabsorption of sodium in the blood is associated with potassium removal from the blood, so that hypokalemia can happen with an excess reabsorption of sodium in the body.

Diagnosis

Physicians will usually order for an evaluation of a child’s blood electrolytes and aldosterone level, together with other tests. Blood and urine tests may reveal decreased blood potassium levels, metabolic alkalosis with high sodium plasma levels, decreased or normal plasma levels of aldosterone and renin, and the low rates of urinary excretion of aldosterone and sodium together with the high rates of urinary potassium levels being excreted. Some medical practitioners shall request a genetic study of the ENaC sequences to detect mutation changes and confirm the diagnosis.

Treatment for Liddle Syndrome

Treatment for Liddle’s syndrome is directed at lowering the blood pressure level, correcting hypokalemia and acidosis. A low-sodium, low salt diet is encouraged. Physicians prescribe potassium-sparing diuretics to block the sodium channels and examples of these are the amiloride and triamterene.

Prognosis

Prognosis is good with proper treatment done once the problem is assessed and evaluated well in a patient based on the clinical manifestation of symptoms. If the hypertension problem is being left untreated over a long period of time, it may end up with the development of a heart disease or stroke, and renal complications may happen which can be fatal to the health status of the patient.

Survival Rate

The rate of survival among patients greatly varies since the occurrence of hypertension among affected members in the family may not be as severe with the others. This is basically true because there can be other factors like genetic and lifestyle events of each individual person which can possibly change the blood pressure level in the body.

References:
1. http://ghr.nlm.nih.gov/condition/liddle-syndrome
2. http://www.medscape.com/viewarticle/547662_7
3. http://www.uptodate.com/contents/genetic-disorders-of-the-collecting-tubule-sodium-channel-liddles-syndrome-and-pseudohypoaldosteronism-type-1
4. Rossier BC, Schild L (October 2008). “Epithelial sodium channel: mendelian versus essential hypertension”. Hypertension 52 (4): 595–600.
5. Sigurjonsdottir HA, Axelson M, Johannsson G, Manhem K, Nyström E, Wallerstedt S (2006). “The liquorice effect on the RAAS differs between the genders”. Blood Press. 15 (3): 169–72.
6. Armanini D, Calò L, Semplicini A (June 2003). “Pseudohyperaldosteronism: pathogenetic mechanisms”. Crit Rev Clin Lab Sci 40 (3): 295–335.