Introduction
Liddle syndrome is a rare condition of resistant or secondary hypertension or high blood pressure in early childhood. However, in some cases, it is not detected until adulthood. Dr. Grant Liddle first explained this in 1963 and termed it pseudo-aldosteronism. It is a rare cause of secondary hypertension (hypertension caused by other medical conditions), which occurs due to a genetic mutation affecting the function of the collecting tubule sodium channel (present in the kidneys).
What Is Liddle Syndrome?
Liddle syndrome is characterized by severe hypertension that begins in early childhood. It shows the classic triad of -
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Hypertension (high blood pressure).
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Hypokalemia (low blood potassium levels due to excessive loss of potassium from the digestive tract because of vomiting, diarrhea, or laxative use).
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Metabolic alkalosis (elevation of pH of the body above 7.5 (acidic) leading to complications affecting the heart, liver, and kidneys).
However, some people do not even experience signs or symptoms, especially in childhood. Still, over time, untreated hypertension can lead to heart disease, which may be fatal.
What Is the Etiology of Liddle Syndrome?
Liddle syndrome is an inherited condition caused by a single gene mutation. Different ethnic groups can be affected by this syndrome. In 1995, Hansson et al. discovered the mutation in gene SCNN1G causing Liddle syndrome. Later on, after various types of research, it was found that 31 different gene mutations can be responsible for Liddle syndrome.
What Is the Epidemiology of Liddle Syndrome?
Liddle syndrome is a rare disorder reported in less than 80 families till now. Because of this reason, the overall population prevalence is unknown. In most cases, patients with this syndrome can remain asymptomatic for up to 40 years, but it can still be diagnosed as early as 12 years of age.
What Are the Signs and Symptoms of Liddle Syndrome?
As already explained, children with Liddle syndrome are primarily asymptomatic. However, the first indication of the syndrome is often high blood pressure (hypertension), which can be found during a routine physical examination.
1. Resistant Hypertension -
Early onset secondary hypertension is usually present between the ages of 11 to 31 years of age due to sodium reabsorption in the kidney nephrons. Hypertension (resistance) caused by Liddle syndrome is diet-sensitive, especially diets containing high salt content, which can lead to the following conditions if left untreated such as -
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Dizziness.
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Retinopathy (a complication of diabetes that affects the eyes).
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Chronic kidney disease.
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Left ventricular hypertrophy (thickening of the walls of heart chambers).
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Sudden death.
Resistant hypertension can also lead to lethal arrhythmias, potentially leading to sudden death.
2. Hypokalemia -
This is the other condition that occurs due to excessive potassium loss in the urine at the expense of sodium reabsorption, which can lead to -
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Muscle weakness.
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Polyuria (excessive urination).
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Polydipsia (excessive thirst).
Some other symptoms which can be seen in adults related to low blood potassium (hypokalemia) include -
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Weakness.
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Fatigue.
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Palpitations.
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Muscular weakness.
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Shortness of breath.
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Constipation.
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Abdominal distention.
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Exercise intolerance.
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Renal insufficiency (improper functioning of kidneys such as concentration of urine, removal of wastes, maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism).
The patients with Liddle syndrome show 92.4 percent and 71.8 percent incidence rates of hypertension and hypokalemia, respectively. Genetic testing is advised in patients who do not have hypertension or hypokalemia to confirm the diagnosis because of significant family history.
What Is the Diagnosis of Liddle Syndrome?
Patient affected with Liddle syndrome often shows secondary or resistant hypertension. The patients are advised to take blood or urine tests to make the diagnosis. Upon laboratory investigation, patients with Liddle syndrome can have hyperaldosteronism, a condition in which adrenal glands produce too much aldosterone (a hormone responsible for regulating blood pressure in the body by controlling the levels of potassium and sodium in the blood). The renin and aldosterone levels should be checked to differentiate between true hyperaldosteronism (a disorder in which the adrenal gland secretes high aldosterone hormone in the blood) and pseudo-hyperaldosteronism (disorder resembling hyperaldosteronism). Patients with Liddle syndrome have low aldosterone levels compared to those with hyperaldosteronism.
Once the patient is diagnosed with low renin and aldosterone levels, they have been prescribed aldosterone for at least two months and are observed. The health care professional can determine Liddle syndrome if the patient does not respond to this treatment. However, the final diagnosis can only be made by genetic testing of the mutated gene SCNN1G.
What Is the Treatment for Liddle Syndrome?
In patients with Liddle syndrome, the drug of choice is Amiloride, which affects sodium reabsorption in the kidney nephrons. This drug can be prescribed daily with a dose of 5-20 mg (milligrams). In addition, Triamterene, a drug similar to Amiloride, can also be prescribed. Along with these drugs, patients are advised to have a sodium and potassium-restricted diet.
What Are the Complications of Liddle Syndrome?
The complications of Liddle syndrome include disorders like hypokalemia, metabolic alkalosis, and resistant hypertension. Moreover, patients with resistant hypertension can develop some severe conditions, such as -
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Myocardial infarction (blockage of blood flow to the heart or heart attack).
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Transient ischemic attack (symptoms like stroke).
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Pulmonary edema (too much fluid in lungs).
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Ventricular hypertrophy (thickening of the heart’s wall).
What Is the Prognosis of Liddle Syndrome?
Liddle syndrome is rare, and patients with this disease respond well to medical therapy involving drugs such as Amiloride. Because of less disease occurrence, long-term mortality data is unavailable. In most cases, clinicians often misdiagnose this condition, which can lead to serious complications if not treated on time.
Although, patients should be warned about the harmful effects of resistant hypertension and should be educated about the treatment to minimize complications such as heart attack and stroke. In addition to that, regular follow-up is required to keep a check on the progress of the treatment.
Conclusion:
Liddle syndrome is an uncommon condition and can lead to adverse clinical outcomes if not treated on time. Therefore, early diagnosis is essential to help treat this condition, as clinicians mostly misdiagnose it. In addition, patients should be aware of the symptoms and guided thoroughly to avoid complications. It is highly recommended that genetic counseling be provided to the patient and family members to diagnose this condition.
