Barth syndrome
Introduction
Introduction to Barth Syndrome Bart's syndrome, Bartter's syndrome, is characterized by hypokalemia, hypervolemia, aldosterone, but normal blood pressure, hyperthyroidism and hypertrophy. Early manifestations of polyuria, polydipsia, constipation, anorexia and vomiting, more common in children under the age of 5, has been considered a clinical syndrome caused by ion channel gene mutations. basic knowledge Sickness ratio: 5% Susceptible population: common in childhood Mode of infection: non-infectious Complications: vitamin D deficiency
Cause
The cause of Barth Syndrome
Cause:
Genetic factors (68%):
Recessive hereditary disease, once reported in 5 out of 9 siblings and 4 consecutive cases in 4 cases, modern molecular biology techniques also revealed that Bartter syndrome is an ion transporter on renal tubular epithelial cells Caused by gene mutation, 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 mutations have been discovered. The classic Bartter syndrome is caused by a mutation in the CICNKB gene, which is located at 1q38 and encodes a basal side of the 687 amino acid Cl-channel. About 20 mutation types have been found in adults. Type 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 some patients, the potassium channel gene (ROWK) mutation is found, so Batter syndrome can be identified as a clinical syndrome caused by mutations in several ion channel genes mentioned above.
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.
Prevention
Barth Syndrome Prevention
The symptoms of infancy are severe, one third of them have mental retardation, and they may die due to dehydration, electrolyte imbalance and infection. After the age of 5, almost all of them have growth retardation, some patients have progressive renal insufficiency, and even develop acute. Renal Failure. Of the 11 deaths reported, 10 were under 1 year of age and died of dehydration, electrolyte imbalance or repeated infections. Older adults and adults died of chronic renal failure.
Promote high potassium and high sodium diet to prevent urinary tract infections. There is no effective preventive measure for this disease, mainly to prevent chronic nephritis, interstitial nephritis, pyelonephritis and other diseases.
Complication
Barth Syndrome Complications Complications vitamin D deficiency
Electrolyte disorders complicated by hyperuricemia, renal calcification, gout kidney and kidney stones and intestinal obstruction and mental naivety. The main complications of children are developmental disorders, vitamin D deficiency, mental retardation and special face. In severe cases, progressive renal failure can occur.
Symptom
Barth Syndrome Symptoms Common symptoms Intestinal paralysis hypokalemia hypokalemia polydipsia polyuria convulsions tremor
The clinical manifestations of this disease are diversified, the clinical types are different, the incidence is more common in adolescents, there is no significant difference in gender, no racial differences, if the understanding of the disease is raised, it is not necessarily rare in clinical, due to complications and complications. The emergence of clinical, often difficult to timely and accurate diagnosis.
The instinct is often misdiagnosed as other diseases due to low blood potassium. The authors propose the diagnosis as follows:
1 has low potassium performance;
2 blood potassium, sodium, chlorine, magnesium reduced;
3 alkali poisoning;
4 urinary potassium, chlorine increased;
5 low urine specific gravity, alkaline urine;
6 plasma renin, angiotensin, aldosterone increased;
7 blood pressure is normal;
8 renal biopsy has hyperrenal growth, hypertrophy;
9 The blood vessel wall has a low response to endogenous or exogenous AII;
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 reason for patients to visit is hypokalemia and alkalosis, its clinical manifestations are: fatigue, weakness, lower limbs or soft body cycle Sexual paralysis; dysfunction, arrhythmia, abdominal distension, intestinal paralysis, intestinal obstruction, nausea, vomiting, difficulty urinating, syncope, mental retardation, slow reflex, weakened or disappeared tendon reflexes; hypokalemia can occur Impaired glucose metabolism, impaired glucose tolerance, insulin release is affected, EEG has abnormal wave pattern, blood potassium <3.0mmol/L, urinary potassium>50mmol/24h or more, alkalosis and hypokalemia often occur simultaneously, with numbness of hands and feet , convulsions, shortness of breath, mental excitement or agitation, muscle tremors and abdominal pain, Chvostek and Trosseau signs positive, blood pH > 7.45, plasma: HCO3- often > 24mEg / L, urine alkaline reaction, early patient urine volume Increase, up to 5000 ml per day, the specific gravity is reduced, urine osmotic pressure is reduced, although patients have convulsions, but blood calcium, phosphorus, AKP, urinary calcium can be 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, blood sodium <130mmol / L, blood chlorine <90mmol / L, urine sodium, increased urinary chlorine discharge, effective blood volume reduction, distal convoluted tubules and ball side devices Further changes have led to 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: not uncommon, this disease can often have pyelonephritis, interstitial nephritis, salt-salt nephritis, glomerulonephritis with renal calcification, kidney stones, hydronephrosis, renal dysfunction Other manifestations, due to chronic renal disease prolonged unhealed, may occur renal osteopathy, osteoporosis, tooth loss, secondary hyperparathyroidism and other performance, and may have increased urinary phosphorus and diabetes, Meget reported a group In patients with Barth Syndrome, urate metabolism is abnormal due to abnormal renal function, uric acid clearance is decreased, urinary urate excretion is reduced, blood uric acid level is elevated, hyperuricemia occurs in 50% of patients, and 20% of patients Acute gouty arthritis occurs, the incidence of gout in normal people is only 0.2% to 0.3%, while 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, including 3 cases of hypercalciuria, Bart syndrome with renal calcification, kidney stones, hypercalciuria is not uncommon, the stone properties can be calcium oxalate, calcium phosphate, urate or mixed Sex, serum uric acid value>7.0mg / dl for hyperuricemia, urine uric acid normal value of 0.5 ~ 0.8g / 24h, normal uric acid clearance rate of 6 ~ 12ml / min, while Barth Syndrome discharge decreased, urine The calcium value varies greatly from region to region. Generally speaking, if it is higher than 200-250mg/24h, it is high-calcium calcium, and the reason for the increase of urinary calcium should be sought.
Examine
Barth Syndrome
Check more common urinary potassium, increased chlorine discharge, elevated urine pH, decreased urine specific gravity, blood AII, AI and ALD were significantly increased.
Blood magnesium should be routinely checked, and those with low blood magnesium should be supplemented with magnesium at the same time.
1. Blood potassium, sodium, and chlorine are lower than normal.
2. The blood pH can be higher than 7.46 for alkalemia, and C02CP is higher than 30mmol/L.
3. Plasma renin activity (PRA) increased to (4.5 ± 2.9) g / L · h or more.
4. The blood aldosterone (Aldo) value increased to 101 ± 9 ng / L.
5. Blood PGA, PGE, PGF, PGI can be increased, such as PGF up to (138.0 ± 78.0) ng / ml.
6. Angiotensin II (Ang II) increased to (95.8 ± 35.2) ng / L.
7. Renal function test: BUN can be increased by more than 7.0mmol/L, the proportion of Maosen test is low, the amount of nocturia is increased, and there are proteins and red blood cells in the urine.
8. In the later stage of renal dysfunction, blood calcium decreased, blood phosphorus increased, AKP increased, uric acid increased, creatinine increased, PTH increased, and secondary hyperparathyroidism was observed.
9. Urine 17-OHCS, urine 17-KS is mostly in the normal range.
1. Intravenous pyelography: abnormalities such as kidney stones and hydronephrosis can be found.
2. Electrocardiogram: hypokalemia can be found.
3. Abnormal kidney map.
4. Renal biopsy: hypertrophy of the renal glomerular can be found in renal biopsy, there are increased number of paraventricular cells, dense plaque cells, pericytes and extracellular mesangial cells, or cells with hypertrophy, 95% Renin is secreted by paracellular cells, and 1% to 5% can produce renin by dense plaque cells, mesenchymal cells or ectodermal endothelial cells.
Diagnosis
Diagnosis of Barth Syndrome
Batter syndrome differs from other diseases with aldosteronism in that there is no hypertension (primary aldosteronism with hypertension) and edema (secondary aldosteronism with edema), adults need to exclude: bulimia In case of vomiting or private diuretics or laxatives, urinary chloride is often low (<20mmol/L).
1. Primary and secondary aldosteronism: primary aldehyde has a significant increase in blood pressure, secondary aldosteronism such as cirrhosis, heart failure, chronic nephritis and pregnancy toxemia have clinical manifestations of primary disease In addition, the original aldehyde has a decreased plasma renin activity.
2. Periodic causes caused by other causes: such as primary recurrent sputum, hyperthyroidism, type I chronic renal tubular acidosis, gossypol poisoning, etc., these diseases have no plasma renin activity and aldosterone increase, hyperthyroidism has T3 and T4 are elevated.
3. Renal tubular acidosis has a decrease in blood pH and CO2 binding, and gossypol poisoning has a history of edible cottonseed oil, which can be distinguished from this syndrome.
4. False Barth Syndrome: Patients with long-term use of loop diuretics may develop pseudo-Bart syndrome, which can be identified according to medical history.
