Liddell syndrome
Introduction
Introduction to Liddell syndrome Liddlesyndrome, clinical manifestations of hypertension, hypokalemia, metabolic alkalosis, clinical symptoms like primary aldosteronism, but its plasma aldosterone levels are very low, and the mineralocorticoid receptor antagonist drug spironolactone It is not effective, so it is also called pseudo-aldosteronism. basic knowledge The proportion of illness: 0.005% Susceptible people: no special people Mode of infection: non-infectious Complications: myocardial infarction, arrhythmia, swelling
Cause
The cause of Liddell's syndrome
(1) Causes of the disease
The basic lesion of Liddell's syndrome is the , subunit gene mutation in the renal tubular epithelial cell amiloride-sensitive sodium channel (ENaC), which prevents the regulation of protein binding to the -, -subunit carboxyl-terminal proline-rich The area exposes a large amount of active ENaC to the apex of the luminal membrane, resulting in an increase in the number of channels on the luminal membrane, an increase in activity, an increase in sodium reabsorption, and an increase in potassium excretion.
(two) pathogenesis
ENaC is located in the renal distal convoluted tubules, the collecting tubules, the cortical and medullary collecting epithelial cell membranes on the apical side of the luminal membrane, which can absorb the sodium ions (Na+) in the luminal fluid into the epithelial cells by electrochemical gradient, and then the substrate. The side Na+-K+-ATPase is pumped into the intercellular space and reabsorbed into the blood. ENaC is the rate-limiting step of sodium reabsorption and is an important factor in maintaining the homeostasis and blood pressure of extracellular fluid. The channel is sodium and lithium. Specificity, can be specifically blocked by triamterene or amiloride, can regulate the activity of ENaC through the ubiquitination and endocytosis of the C-terminus of the cytosol, aldosterone, vasopressin, insulin and Regulatory pathways including the cytoskeleton and protein kinases A, C regulate their activity.
ENaC consists of three subunits: , , and . All three have two transmembrane domains, one large extracellular domain and two short cytoplasmic tails, and the exact role of three subunits. It is not fully understood that the alpha subunit may be the basic structural unit, which is indispensable for the function of the channel; the , subunit is the unit of activity regulation, and the 3 subunits have 35% homology, but their cytoplasmic tails There is a highly conserved proline-rich region (P2 region) containing a sequence of PPPxY (P for proline, Y for tyrosine, X for any amino acid), called PY motif, chaperone protein The WW domain of the progressive down-regulated gene 4 isoform (Nedd4) expressed by YAP65 and ubiquitin ligase neural precursor cells can be specific to the proline-rich P2 region of the PY motif of the normal , subunit. It is phosphorylated by binding and/or inhibits the activity of ENaC by clathrin-mediated endocytosis.
So far, 12 gene mutations of Liddell's syndrome have been identified, both located in the cytoplasmic tail of the , subunit. The ENaC, which is terminated early due to missense mutation or frameshift mutation, is called Liddle channel. This channel has higher activity than the wild-type ENaC, so that the WW domain of YAP65 protein and Nedd4 protein cannot bind to the PY motif on the , subunit, which reduces the inversion of ENaC into the cell, and a large amount of active ENaC is exposed to the cavity. At the top of the membrane, the number of channels on the cell membrane increases, activity increases, sodium reabsorption increases, blood volume expands, blood pressure rises, aldosterone and renin secretion are inhibited, potassium reabsorption is reduced, and a series of clinical symptoms appear, although The intracellular sodium is high, the ENaC activity is still not down-regulated, and the feedback regulation of EN+C by Na+ is impaired. After the intake of low sodium, the decrease of urinary sodium is not as good as that of normal people.
Liddell's syndrome Although the plasma aldosterone level is very low, the kidney still sputum sodium and potassium, inhibits the synthesis of aldosterone and inhibits the peripheral activity of aldosterone, has no effect on urine electrolytes, and reacts with salt and salt-sparing diuretics and sodium load. Capacity-expandable hypertension is consistent, and triamterene is effective, but most patients can not control blood pressure with ampicillin alone. The effect is better after adding upper limit salt, suggesting that the proximal tubule of the site of triamterene is also There is a phenomenon in which Na+ is excessively reabsorbed.
Kidney transplantation was performed in patients with Liddell's syndrome after renal failure. The results showed that all indicators (including blood pressure and blood, urine and electrolytes) were converted to normal, which proved that the lesion was in the kidney itself. Most of the results of intravenous pyelography were normal. Renal biopsy It was found that the proximal mesangial membrane had clastic changes; the renal glomerular atrophy, the renin particles were few, and the increase in plasma renin and aldosterone levels after salt limitation also reflected the atrophy of the glomerular device; In the case of the increase in the content of glomerular cells, occasionally adhesions.
Prevention
Liddell syndrome prevention
The disease is a rare autosomal dominant genetic disease. At present, there is no effective prevention method. In the diagnosis and treatment of hypertension, it is necessary to be alert to the existence of the disease. When suspicious signs are found, further examination is required. Early detection and early treatment to prevent complications.
Complication
Lyle syndrome complications Complications myocardial infarction arrhythmia swelling
Liddell's syndrome, like any other cause of hypertension, can cause a variety of complications. Liddell syndrome family members die in stroke, myocardial infarction, arrhythmia (especially with coronary artery disease) and heart failure Increased risk; renal progressive sclerosis, renal failure, but this is because the characteristics of the disease itself is still unclear, long-term hypokalemia can cause Kalifopenic nephropathy, accompanied by The cloud-like swelling of the curved tubules and the changes in the function of the distal tubules cause the kidneys to acidify the urine, reduce the acid load and reduce the ability to concentrate the urine.
Symptom
Liddell syndrome symptoms common symptoms hypokalemia hypertension metabolic alkalosis polyuria sensory disorder inability to polydipsia polydipsia convulsions rhabdomyolysis
The typical clinical manifestations of Liddell's syndrome patients are hypertension, hypokalemia, and metabolic alkalosis. The clinical phenotype is greatly affected by gene penetrance and environmental factors. Some patients have elevated blood pressure and normal blood potassium. Some patients have low blood potassium and normal blood pressure. Some patients have normal blood pressure and blood potassium and low aldosterone levels. The level of plasma HCO3- is also very different. Some patients have no metabolic alkalosis, while some patients have HCO3- The level is very high. Generally speaking, the lower the blood potassium level, the higher the level of plasma HCO3-, the clinical manifestation of Liddell syndrome:
Hypertension
It is the earliest symptom and the most common symptom. It is more common in adolescents and is more serious. Patients often see this symptom.
2. Electrolyte disorders
Hypokalemia is also a common symptom, but about 50% of patients have high blood pressure and normal potassium, and blood potassium is generally 2.4 to 2.8 mmol/L; sometimes only mildly low potassium, 3.0 to 3.6 mmol/L, potassium. Very low (1.8 ~ 2.2mmol / L) is rare, metabolic Alkalosis plasma HCO3-level increased, arterial blood pH increased, blood sodium increased, plasma renin, aldosterone levels, urinary sodium decreased, urine Potassium increases and urine aldosterone levels are low.
3. Low potassium performance
Such as muscle weakness, periodic paralysis, hand and foot convulsions, and even rhabdomyolysis (with elevated plasma creatine phosphokinase), paresthesia; polyuria, polydipsia.
Examine
Liddell's syndrome check
1. The blood potassium is generally 2.4 to 2.8 mmol/L, and sometimes only mildly low potassium, 3.0 to 3.6 mmol/L, and extremely low potassium (1.8 to 2.2 mmol/L) are rare.
2. Metabolic alkalosis plasma HCO3-level increased, arterial blood pH increased, blood sodium increased, plasma renin, aldosterone levels were low, urinary sodium decreased, urinary potassium increased, urine aldosterone levels were low.
Diagnosis
Diagnosis and differentiation of Liddell syndrome
Diagnostic criteria
The main diagnosis of Liddell's syndrome is hypertension, hypokalemic metabolic alkalosis, low plasma renin and low plasma aldosterone. Early diagnosis of this disease is important because good treatment can control clinical symptoms and prevent complications. Quality of life and life expectancy such as normal people, history of headache, muscle cramps, paresthesia, convulsions of the hands and feet or muscle weakness, especially those who have died in previous generations, suggesting the possibility of Liddell syndrome, according to clinical symptoms, experiments Laboratory tests showed high blood sodium, hypokalemia, metabolic alkalosis, low levels of plasma renin and aldosterone, and ineffective spironolactone.
Differential diagnosis
1. Primary hyperaldosteonism (primary aldehyde) Primary aldehyde due to adrenocortical autonomous secretion of aldosterone, resulting in sodium, potassium, causing hypertension, hypokalemia with alkalosis and other clinical manifestations, common The reason is adrenal adenoma or hyperplasia, aldosterone determination showed 24h urinary aldosterone and plasma aldosterone were significantly increased, renin-angiotensin levels were reduced, abdominal CT or MRI showed adrenal adenoma or hyperplasia can be identified, spironolactone treatment or surgery Resection of adenomas and hyperplasia is effective.
2. Bartter syndrome (glomerular hyperplasia) Bartter syndrome is characterized by severe hypokalemia, alkalosis, low blood sodium, low chloride, normal blood pressure, polydipsia, polyuria, constipation, dehydration, Plasma renin-angiotensin and aldosterone are elevated, pathological changes in the growth of the juxtaglomerular apparatus and adrenal spheroidal stellate zone, the pathogenesis is unknown, indomethacin, aspirin and other symptoms can be resolved.
3. Syndrome of apparent mineralocorticoid excess (SAME) SAME is a deficiency of congenital 11-beta hydroxysteroid dehydrogenase (11-0HSD), which is located at 16q22.1, and its role is to Cortisol is locally converted to inactive cortisol in the renal tubule. Congenital 11-OHSD deficiency is an autosomal recessive disorder. Due to the lack of 11-OHSD, plasma cortisol levels are elevated due to mineralocorticoid receptors and sugar. Corticosteroid receptors have high homology in amino acid sequence. Therefore, excessive cortisol binds to mineralocorticoid receptor and exerts mineralocorticoid-like effects. Patients have high blood pressure and hypokalemia during adolescence. The lack of secondary sexual characteristics is an important clinical feature.
4. Glucocorticoid-inhibitory aldosteronism Glucocorticoid-inhibitory hyperaldosteronism is an autosomal dominant genetic disease with high penetrance and high aldosterone and low renin. Related to aldosterone synthase gene mutation, aldosterone synthase is ectopically expressed in the adrenal cortical bundle, is regulated by ACTH excitability, sensitive to ACTH stimulation, resulting in increased aldosterol secretion, sodium retention, and elevated blood pressure. The disease is more common in adolescent males. The adrenal gland is large and small nodular hyperplasia. The plasma aldosterone level is parallel to the circadian rhythm of ACTH. After several weeks of physiological replacement of glucocorticosteroids, aldosterone secretion, blood pressure and blood potassium can be restored to normal. .
5.17-hydroxylase deficiency syndrome 17-hydroxylase deficiency syndrome is an autosomal recessive disorder. It has been found that there are at least 18 different types of mutations in this gene, and most of the mutations completely destroy the 17-hydroxylase. Activity, the lack of this enzyme can prevent the conversion of pregnenolone and progesterone to 17-hydroxypregnenolone and 17-hydroxyprogesterone, which reduces or even completely lacks deoxycortisol and cortisol, and increases the reactivity of ACTH secretion. Excessive production of deoxycorticosterone (DOC) by salt corticosteroids leads to hypertension, hypokalemia, and secondary sexual assault is an important clinical feature.
6. Acquired pseudohyperaldosteronism Acquired pseudohyperaldosteronism is hypokalemia caused by licorice or mineralocorticoids. Careful consultation with the history of medication may help to confirm the diagnosis.
In addition, patients with essential hypertension may have hypokalemia when taking diuretics without potassium supplementation, but blood potassium can return to normal after the diuretic is stopped and potassium is added.
