History of The Disease / Demographic Data: Age, Sex, Race Distribution in Population
The disease is named after Dr. Grant Liddle, an American endocrinologist working at Vanderbilt University who took the first role in describing the disease (Awadalla, Patwardhan, Alsamsam, and Imran, 2017). He described it as autosomal dominant hypertension with the signs of low renin, aldosterone, and potassium exemplified by heritable genes. Liddle syndrome affects both sexes, including pregnant women. Its onset is during infancy, childhood, Adolescent, and adulthood. It has been identified worldwide, although specific genetic lineage could be distributed non-uniformly (NORD, 2022). However, the Syndrome affects people of all gender, class, race, and ethnicities.
Description of the Disease
Liddle syndrome is a disease due to the characteristics of high blood pressure. The illness is characterized by hypertension that starts early and could likely be diagnosed during adulthood or childhood. In most cases, the symptoms include the signs of stroke. If hypertension in this disease is not managed or treated, the patient could be risking their lives due to the chances of stroke and heart disease (Pagani et al., 2018). Moreover, an individual with high blood pressure could have less potassium in the blood and have fatigue, heart palpitation, and other signs of muscle pain and weakness.
Anatomy of Affected System
Liddle syndrome, a rare hereditary condition affecting the kidneys, is characterized by increased activity of epithelial sodium channels. In this regard, the kidneys excrete potassium while retaining a lot of water and sodium, which results in hypertension (Knight, Olson, Zhou, and Snyder, 2016). The condition’s symptoms include metabolic alkalosis, hypertension, and fluid retention. On the other hand, Liddle syndrome occurs as a rare autosomal and dominant condition affecting renal epithelial transport. It correlates to primary aldosteronism, with low plasma, aldosterone, and renin levels. Also, hypertension and hypokalemic metabolic alkalosis symptoms further prove the condition. The Syndrome occurs from increased activity of the epithelial sodium channels present in the luminal membrane, precisely in the collecting tubule. This accelerates the secretion of potassium and the resorption of sodium, thereby causing potassium retention and sodium excretion.
Effects on Other Body Systems and Complications
The Liddle syndrome is significantly harmful to other body organs, cells, and systems while untreated or not diagnosed on time. For instance, it causes ischemia, renal failure, hypertensive encephalopathy, nephrosclerosis, pulmonary edema, hypertension, and left ventricular hypertrophy. If the disease is misdiagnosed, it is likely to affect the hypoperfusion of the blood in various tissues and organs and cause obstruction or constriction of the various blood vessels like veins and arteries. It also causes complications with the left ventricle muscle of the heart in that it causes a build-up of abnormal volume and pressure that could cause various heart diseases. Moreover, lack of effective management adversely impacts the eye in the retinal vascular and is affected by high blood pressure.
Causes of the Disease
Liddle syndrome is due to the mutation in the SCNN1G gene or SCNN1B genes. Both two genes have the instruction subunit or a piece of a protein complex called the (ENac) epithelial sodium channel (Enslow, Stockand and Berman, 2019). In the kidney, the ENac channel opens to respond to low sodium levels in the blood, hence allowing sodium to get into the cell. Also, the mutation causes truncation in the cytoplasmic C-terminal tail for the affected subunits. The sodium reabsorption collecting duct depends on apical cell membrane channel density. In that case, the channel density is regulated by removing cell membrane ENaC, degradation, or ubiquitination (Tetti et al., 2018). The increase of sodium resorption causes increased hypertension, and water resorption is caused by increased extracellular volume.
Signs and Symptoms
The signs and symptoms of Liddle syndrome that are clinically and biochemically tested include hypokalemic metabolic alkalosis and hypertension, usually as the early-onset. Notably, alkalosis occurs in suppressed plasma renin activity and poor plasma aldosterone concentration. Usually, Liddle syndrome occurs due to the unusual high sodium reabsorption, leading to increased intravascular volume and later leading to arterial hypertension. Elevated pressure in the blood and the low potassium levels in the serum suppresses the system of renin, aldosterone, and angiotensin, thereby leading to hyporeninemia (Furuhashi et al., 2005). Usually, most patients with this Syndrome exhibit severe hypertension, although the severity of these symptoms differs among them. The patients with more severe symptoms can only have mild symptoms such as intermittent headaches, dizziness, visual changes, and fatigue. On the other hand, patients experiencing mutations of this Syndrome might fail to develop any raised blood pressure. Other patients tend to develop end-organ damages like hypertensive retinopathy, nephrosclerosis, and hypertrophy in the left ventricles (Rossi et al., 2011). Symptoms of long-term hypertension in patients also include cerebrovascular accidents, cardiovascular disease, and renal insufficiency.
Liddle Syndrome diagnosis involves hypertension in young patients, especially those with positive family histories. Precisely, low aldosterone, plasma renin, and urine sodium levels are deemed sufficient in confirming the diagnosis (Nesterov et al., 2016). Also, empiric treatment responses provide sufficiency, although a definitive diagnosis requires genetic testing.
There are various options for the treatment and management of Liddle syndrome. Firstly, kidney transplantation completely resolves the problems. Another conventional method is the anti-hypertensive therapies that effectively control the extracellular fluid and hence control the levels of water and sodium in the affected organs. Also, the condition is managed by taking a diet with low sodium and spared potassium-sparing diuretic. Diet is the most used method of managing the condition in that it corrects hypokalemia metabolic alkalosis and reduces blood pressure. Moreover, amiloride is an efficient convention treatment that is the only option available for pregnant women (Awadalla, Patwardhan, Alsamsam, and Imran, 2017). Such a medical treatment does help in correcting hypokalemia and hypertension and may require different potassium replacement therapy.
Current research on the prevalence of Liddle’s Syndrome offers insights regarding the incomplete prevalence data of the Syndrome, thereby implying the underdiagnosis of the disease. Also, research creates awareness on the similarity of the symptoms of this disease to those of other conditions while informing the unpopularity of the Syndrome’s genetic screening. To this effect, proposed research on the attainment of increased population-level genetic screening prevails. Furthermore, non-hypertensives screenings of the Syndrome’s mutations would get recommended to enhance population-level data on the penetrance of the disease. Additionally, prevention strategies for the disease are critical such as constant warnings to patients on the resistant hypertension hazards and compliance to recommended treatment to reduce stroke and heart attack risks. As a result, patients should maintain regular follow-ups and diets with high potassium levels. Early diagnosis of Liddle Syndrome should be a priority as It is crystal clear that there are adverse clinical effects of late diagnosis. Therefore, relevant stakeholders such as pediatrics nephrologists and pediatricians should uphold optimal coordination and offer appropriate genetic counseling.
Awadalla, M., Patwardhan, M., Alsamsam, A., & Imran, N. (2017). Management of Liddle Syndrome in Pregnancy: A Case Report and Literature Review. Case Reports In Obstetrics And Gynecology, 2017, 1-4. https://doi.org/10.1155/2017/6279460
Enslow, B., Stockand, J., & Berman, J. (2019). <p>Liddle’s syndrome mechanisms, diagnosis and management</p>. Integrated Blood Pressure Control, Volume 12, 13-22. https://doi.org/10.2147/ibpc.s188869
Furuhashi, M., Kitamura, K., Adachi, M., Miyoshi, T., Wakida, N., & Ura, N. et al. (2005). Liddle’s Syndrome Caused by a Novel Mutation in the Proline-Rich PY Motif of the Epithelial Sodium Channel β-Subunit. The Journal Of Clinical Endocrinology & Metabolism, 90(1), 340-344. https://doi.org/10.1210/jc.2004-1027
Knight, K., Olson, D., Zhou, R., & Snyder, P. (2016). Liddle’s syndrome mutations increase Na+ transport through dual effects on epithelial Na+ channel surface expression and proteolytic cleavage. Proceedings Of The National Academy Of Sciences, 103(8), 2805-2808. https://doi.org/10.1073/pnas.0511184103
Nesterov, V., Krueger, B., Bertog, M., Dahlmann, A., Palmisano, R., & Korbmacher, C. (2016). In Liddle Syndrome, Epithelial Sodium Channel Is Hyperactive Mainly in the Early Part of the Aldosterone-Sensitive Distal Nephron. Hypertension, 67(6), 1256-1262. https://doi.org/10.1161/hypertensionaha.115.07061
NORD. (2022). Liddle Syndrome – NORD (National Organization for Rare Disorders). NORD (National Organization for Rare Disorders). Retrieved 5 February 2022, from https://rarediseases.org/rare-diseases/liddle-syndrome/.
Pagani, L., Diekmann, Y., Sazzini, M., De Fanti, S., Rondinelli, M., & Farnetti, E. et al. (2018). Three Reportedly Unrelated Families With Liddle Syndrome Inherited From a Common Ancestor. Hypertension, 71(2), 273-279. https://doi.org/10.1161/hypertensionaha.117.10491
Rossi, E., Farnetti, E., Nicoli, D., Sazzini, M., Perazzoli, F., & Regolisti, G. et al. (2011). A Clinical Phenotype Mimicking Essential Hypertension in a Newly Discovered Family With Liddle’s Syndrome. American Journal Of Hypertension, 24(8), 930-935. https://doi.org/10.1038/ajh.2011.76
Tetti, M., Monticone, S., Burrello, J., Matarazzo, P., Veglio, F., & Pasini, B. et al. (2018). Liddle Syndrome: Review of the Literature and Description of a New Case. International Journal Of Molecular Sciences, 19(3), 812. https://doi.org/10.3390/ijms19030812.