Soft paralysis of lower extremities or whole body
Introduction
Introduction Lower limbs or soft palate in the whole body is a symptom of the abnormality of water and salt metabolism in Barth Syndrome. The cause of this disease is still inconclusive. Most scholars believe that it is an autosomal recessive hereditary disease. The clinical manifestations of this disease are diversified, the clinical types are different, the incidence is more common in adolescents, gender is not significantly different, and there is no ethnic difference. If the understanding of the disease is raised, it is not necessarily rare in clinical practice. Due to the occurrence of complications and complications, it is often difficult to diagnose in time and accurately.
Cause
Cause
(1) Causes of the disease
The cause of this disease is still inconclusive. Most scholars believe that it is an autosomal recessive hereditary disease. There have been reports of 5 out of 9 compatriots and 4 cases of 2 consecutive generations. Modern molecular biology techniques have also revealed that Bartter syndrome is caused by mutations in the ion transporter gene on renal tubular epithelial cells. It has been found that there is a Na-K-2Cl-gene mutation in infant Batter syndrome. The gene is located at 15q12-21 and has 16 exons encoding 1099 amino acids, which is Na-K-2Cl-channel. More than 20 have been found. Mutations. The classical Bartter syndrome is caused by a mutation in the CICNKB gene, which is located at 1q38, encoding a basal side of the 687 amino acid Cl-channel, and has now found about 20 mutation types. Adult Bartter syndrome, also known as Batter-Gietlman syndrome, is caused by a mutation in the thiazide-sensitive Na-K channel gene (SCI12A3), which is located at 16q913, encoding 1021 amino acids, and has found up to 40 mutations. In addition, potassium channel gene (ROWK) mutations have been found in some patients. Therefore, Batter syndrome can be identified as a clinical syndrome caused by mutations in several ion channel genes described above.
(two) pathogenesis
The pathogenesis of this disease has not been fully elucidated. Some people have proposed four hypotheses about the pathogenesis of this syndrome:
1. Defects in the response of the vessel wall to ATI lead to increased renin production and secondary aldosterone increase.
2. The proximal small tube sodium reabsorption disorder leads to a negative sodium balance; the low sodium diet can not reverse the renal potassium loss.
3. Excessive production of prostaglandins causes loss of sodium in the renal tubules and reduction of blood sodium to activate the renin-angiotensin system.
4. The thick wall segment of the medullary palpebral pallidus has a barrier to chloride translocation, which reduces the reabsorption of chloride, and the increase of potassium excretion leads to hypokalemia; hypokalemia stimulates the production of prostaglandin E2 and makes plasma renin activity and Angiotensin I is elevated. After prostaglandin E2 elevation, the blood vessels are not sensitive to ATI and the blood pressure is normal.
In recent years, clinical and experimental studies have made great progress in understanding the pathogenesis of Bartter syndrome. It is believed that Bartter syndrome is caused by the translocation of Cl- and Na in the thick-walled segment of the medullary ascending branch. At present, the gene coding of several ion channel proteins of the ascending medulla has been cloned, and the ion transport function has been impeded by the mutation of these ion channel proteins. The normal renal unit medullary ascending thick wall segment (Fig. 1) is responsible for the reabsorption of Cl- and Na by the bumetanide-sensitive sodium-potassium-2-chloride transporter. , NKCC2). Since Na and C1- are lower in cells than in cells, NKCC2 operates Na, K, and 2Cl- into cells, and remains electrically neutral. Na-K-ATPase on the basal side membrane of epithelial cells can pump excess Na out of the cell and into the bloodstream.
In addition, a kidney-specific base lateral channel (CIC-kb) pumps Cl- out of the cell and reabsorbs it through the blood. There is also ATP-regulated potassium channel (ROMK) on the luminal membrane on the thick wall of the medullary ascending branch. The transport rate of NKCC2 is regulated by ROMK for potassium recirculation, ie ROMK provides a valid K concentration for NKCC2, ensuring a positive potential of the lumen.
Examine
an examination
Related inspection
Random exercise check urine routine blood routine
Diagnosis: The clinical manifestations of this disease are diversified, the clinical types are different, the incidence is more common in adolescents, gender is not significantly different, and there is no ethnic difference. If the understanding of the disease is raised, it is not necessarily rare in clinical practice. Due to the occurrence of complications and complications, it is often difficult to diagnose in time and accurately.
Intrinsic is often misdiagnosed as other diseases due to low blood potassium. The authors proposed the diagnosis as follows: 1 low potassium performance; 2 blood potassium, sodium, chlorine, magnesium decreased; 3 alkali poisoning; 4 urinary potassium, chlorine increased; 5 low urine specific gravity, alkaline urine; 6 plasma renin, vascular tension Increased aldosterone; 7 normal blood pressure; 8 renal biopsy with hyperrenal hyperplasia, hypertrophy; 9 vascular wall response to endogenous or exogenous AII is low; 10 prostaglandin levels increased.
Fluid, electrolytes and hormones are abnormal at the same time, characterized by potassium, sodium and chlorine consumption, hypokalemia, hyperaldosteronism, hyperrenalemia and normal blood pressure.
1. Water and salt metabolism disorders: The most common, prominent manifestations of hypokalemia alkalosis. The main cause of the patient's visit is hypokalemia and alkalosis. The clinical manifestations are: fatigue, weakness, and periodic paralysis of the lower extremities or the soft palate in the body; feeling dull, arrhythmia, bloating, intestinal paralysis, intestinal obstruction, nausea, vomiting Dysphagia, syncope, mental retardation, slow reflexes, weakening or disappearance of sputum reflexes, etc.; hypoglycemia can cause disorders of glucose metabolism, impaired glucose tolerance, insulin release, and abnormal EEG patterns. Blood potassium 50mmol / 24h or more. Alkali poisoning and hypokalemia often occur at the same time, there are numbness of hands and feet, convulsions, shortness of breath, mental excitement or agitation, muscle tremor and abdominal pain, Chvostek and Trosseau signs positive, blood pH >7.45, plasma: HCO3-constant>24mEg /L, the urine is alkaline. In early patients, the amount of urine increased, reaching more than 5000 ml per day, the specific gravity decreased, and the osmotic pressure of urine decreased. Although patients had convulsions, blood calcium, phosphorus, AKP, and urinary calcium were normal.
Due to dehydration and salt loss, patients often have dry mouth, thirst, halophilic, polydipsia, polyuria, nocturia, weight loss, weight loss, constipation, poor skin elasticity, deep eye sockets, low intraocular pressure, and less urinary dehydration. , only 300 ~ 400ml per day, can occur collapse, mental disorder or coma. Increased blood sodium, sodium and urine, increased urinary chlorine volume, decreased blood volume, and further changes in the distal convoluted tubules and the ball side, resulting in increased secretion of renin, prostaglandins, angiotensin and aldosterone.
Zipser reported two cases of this disease, one of which had severe hypomagnesemia. The authors believe that hypomagnesemia can also excite the increase of renal PG and cause Barth syndrome, or for other reasons, further research is needed.
2. Kidney disease as the main clinical manifestation type: It is not uncommon for this disease to have pyelonephritis, interstitial nephritis, salt-salt nephritis, glomerulonephritis with renal calcification, kidney stones, hydronephrosis, renal dysfunction Performance. Due to the prolonged unhealed chronic kidney disease, renal osteodystrophy, osteoporosis, tooth loss, and secondary hyperparathyroidism may occur. There may be an increase in urinary phosphorus and diabetes. Meget reports a group of patients with Barth Syndrome, abnormal urate metabolism due to abnormal renal function, decreased uric acid clearance, decreased urinary urate excretion, elevated blood uric acid levels, and hyperuricemia in 50% of patients 20% of patients develop acute gouty arthritis. The incidence of gout in normal people is only 0.2% to 0.3%, while the patients with Barth Syndrome have a significant increase in gout, and gout can also be one of the clinical manifestations of Barth Syndrome. MeCrldie reported 4 cases of this disease, 3 of which had hypercalciuria. Barth Syndrome with renal calcification, kidney stones, and hypercalciuria are not uncommon. The stone properties can be calcium oxalate, calcium phosphate, urate or a combination. Hyperuricemia was found in patients with serum uric acid value >7.0 mg/dl. The normal value of uric acid in urine is 0.5-0.8 g/24h, the normal uric acid clearance rate is 6-12 ml/min, and the discharge in Barth syndrome is reduced. The urinary calcium value varies greatly from region to region. Generally speaking, if it is higher than 200-250mg/24h, it is high urinary calcium, and the reason for the increase of urinary calcium should be sought.
3. Vasoactive hormone balance disorder performance: Barth syndrome has high prostaglandins, renin, angiotensin and aldosterone, and its hematuria PGA2, PGE, PGF, PGI. Both can be raised, but mainly PGE is elevated. Increased PGA2, PGE, and PGF were all treated with aspirin and returned to normal levels after 3 months. Bowden reported an increase in PGE in 5 of the 7 patients. After treatment with indomethacin, 4 patients had a decrease in PGE, decreased sodium and potassium excretion, increased potassium levels, decreased plasma renin values, and decreased creatinine clearance. Urinary PGE of Barth Syndrome is associated with vasopressin excretion, and hyperreninemia is secondary to an increase in renal PG. The kallikrein-kinin system is associated with the prostaglandin-renin-angiotensin-aldosterone system. Increased activity of the kallikrein-kinin system can stimulate the synthesis of PGE in the kidney. After treatment with indomethacin, PGE, kallikrein, and plasma renin activity can be significantly reduced, and Ang II can increase sensitivity, potassium. Back to normal. AngI also increased in this disease, up to 90 ~ 200ng / ml, and the normal value is only below 50ng / ml level. After using indomethacin, the amount of urinary Aldo can not be reduced, the reason is not clear. Animal experiments have confirmed that plasma renin activity can be increased by injecting PGE and arachidonic acid into the renal artery, and the sensitivity of AngII can be increased by indomethacin, and the renin activity can also be decreased. Fujita did an angiotensin injection test in patients with this disease. It did find that the response to angiotensin was lower than that of normal people, but the application of albumin intravenously increased the reactivity, indicating that the blood vessel wall's anti-stress response to angiotensin is Caused by low sodium, low blood volume, etc. Inada gives patients with this disease a daily intake of 175mmol sodium, and when injected with AngII higher than 20ng/(kg?min), the diastolic blood pressure can be increased by 20mmHg, and the systolic blood pressure is greater than the injection speed of 100ng/(kg?min). Only a slight increase, while the normal person can increase the systolic blood pressure of 20mmHg and the diastolic blood pressure of 20mmHg only at the rate of 20ng/(kg?min). It is obvious that the characteristic patients are not sensitive to the exogenous AngII reactivity.
The increase in PG in Barth Syndrome is primary, and plasma renin activity, angiotensin and aldosterone increase are secondary reactions. Normal plasma Aldo value is 5.0-15.0 ng/dl and Barth syndrome patients can reach 50 ng/dl or more, urine Aldo value is 5.0-20.0 ng/24h, and Barth syndrome can reach 30 ng/24h or higher.
4. Other clinical manifestations The incidence of childhood development often has growth and development disorders, growth stagnation or slow, mental retardation and hypogonadism, but no pituitary dwarfism. In patients with Barth Syndrome, anemia can be combined with renal dysfunction. When dehydration is severe, it may be accompanied by blood concentration, hemoglobin is more than 16 grams, and accompanied by polycythemia.
The diagnosis of Barth syndrome is mainly based on the following points:
1. There are clinical manifestations of hypokalemia, such as weakness, periodic paralysis, nocturia, and low potassium on the electrocardiogram. Children are still young and mentally retarded.
2. Alkali poisoning, manifested as hand, foot and ankle.
3. Blood potassium, sodium and chloride are reduced.
4. Plasma renin activity, blood and 24h urine aldosterone increased.
5. There is no blood pressure elevation response to angiotensin II and vasopressin.
6. Renal biopsy has granulosa cell proliferation of the glomerular balloon.
7. Blood pressure is normal.
8. For congenital persons, molecular biology techniques can be used to examine gene mutations.
Diagnosis
Differential diagnosis
Differential diagnosis of lower limbs or soft palate:
1, lower limb weakness: lower limb weakness is caused by cervical spondylotic myelopathy, manifested as lower limb weakness, numbness, tightness, heavy lifting and other symptoms, gradually appearing limp, trembling, gait shaking, easy to fall, etc. .
Cervical spondylotic myelopathy is a type of cervical spondylosis. Cervical spondylosis can be roughly divided into four types: cervical cervical spondylosis, radiculous cervical spondylosis, vertebral artery type cervical spondylosis, and cervical spondylotic myelopathy. Cervical spondylosis, also known as cervical vertebra syndrome, is a general term for cervical osteoarthritis, proliferative cervical spondylitis, cervical nerve root syndrome, and cervical disc herniation. It is a disease based on degenerative pathological changes. Mainly due to long-term cervical vertebrae strain, bone hyperplasia, or disc herniation, ligament thickening, resulting in cervical spinal cord, nerve root or vertebral artery compression, a series of clinical syndromes of dysfunction. The manifestations of cervical disc degeneration and its secondary pathological changes, such as vertebral instability, loosening; nucleus protruding or prolapse; spur formation; ligament hypertrophy and secondary spinal stenosis, etc., stimulated or oppressed Adjacent nerve roots, spinal cord, vertebral artery, and cervical sympathetic nerves, and cause a variety of symptoms and signs of the syndrome.
2, lower limb swelling and fatigue: lower limb swelling and fatigue is one of the symptoms of deep vein thrombosis.
3, lower extremity muscle spasm: lower extremity muscle spasm is a symptom of spinal cord compression.
4. Whole body dystonia: Dystonia refers to dyskinesia characterized by abnormal movements and postures of muscle tension caused by uncoordinated or excessive contraction of active muscles and antagonistic muscles. Systemic dystonia: refers to 3 or more dystonias of the head and neck, limbs, and trunk muscle groups, such as torsion. Dystonia can be classified into systemic, focal or segmental. Systemic dystonia (deformed dystonia, formerly known as tonic sputum) is a rare progressive syndrome characterized by torsional involuntary movements that cause persistent, often bizarre postures. Symptoms usually begin Appeared in childhood. It is characterized by the inversion of the foot during walking and fixation in the flexion position. Systemic dystonia is often hereditary. The main genetic pattern is autosomal dominant with partial penetrance. In the family of a priori patients, some members who appear to be untreated are often cases of this disease. . In several families, the causative gene appears to be located on chromosome 9q. The pathological and anatomical basis of this disease is unknown. The most severe form of the disease shows an unacceptable steady progression of aggravated disease, and cases with very severe symptoms may often be in a peculiar, fixed posture formed by systemic torsion. Spiritual and thinking functions usually remain normal.
