Fanconi syndrome
Introduction
Introduction to Fanconi Syndrome Fanconiyn syndrome (Fanconisyndrome) is also known as Fanconi-deToni syndrome, osteomalacia-kidney glucosuria-amino aciduria-hyperphosphate syndrome, and various renal tubular dysfunction diseases. Refers to a group of syndromes caused by dysfunction of hereditary or acquired proximal tubules. The clinical manifestations are all-acid urinary such as all-amino acid urinary tract, phosphate urinary, glucose urinary, bicarbonate urinary and uric acid. basic knowledge The proportion of illness: 0.002% Susceptible people: no special people Mode of infection: non-infectious Complications: hypokalemia, kidney stones
Cause
The cause of Fanconi syndrome
There are many causes of this syndrome, which can be divided into primary and secondary. The primary Fanconi syndrome is divided into three types: infant type, adult type and brush border missing type. Secondary Fanconi synthesis The sign includes secondary to hereditary diseases and secondary acquired diseases. The former includes: cystine storage disease, tyrosinemia type I, glycogen storage disease type I, galactosemia, hereditary Fructose intolerance, cytochrome c oxidase deficiency, Wilson disease, Lowe syndrome, hereditary osteogenesis imperfecta, Alport syndrome, congenital nephrotic syndrome, vitamin D-dependent rickets; the latter includes: nephrotic syndrome , transplanted kidney, acute and chronic interstitial nephritis, multiple myeloma nephropathy, Sjogren's syndrome, renal amyloidosis, heavy metal poisoning, drugs (expired tetracycline, amino sugar antibiotics, 6-mercaptopurine, cisplatin, etc.) Caused by kidney damage, hypokalemia, hyperparathyroidism, and tumor-associated nephropathy.
Most children and children are related to heredity, and adults are often secondary to immune diseases, metal poisoning or kidney disease.
Kidney disease (36%):
There are many kinds of kidney diseases, such as glomerulonephritis caused by immune injury and pyelonephritis related to bacterial infection. In addition, patients with diabetes, hypertension and systemic lupus erythematosus often have kidney disease, so we see At the same time, a kidney patient will carefully check whether the patient has other related diseases and understand the cause to give the patient the most appropriate treatment.
Immune disease (35%):
An autoimmune disease is a disease caused by the body's immune response to its own antigen, which causes damage to its own tissues. The existence of autoantibodies is not the same concept as autoimmune diseases. Autoantibodies can exist in normal people without autoimmune diseases, especially in the elderly, such as anti-thyroglobulin, thyroid epithelial cells, gastric parietal cells, nuclear DNA antibodies. Wait.
Genetics (20%):
The occurrence of this disease is related to genetic factors.
Pathogenesis
The pathogenesis of Fanconi syndrome has not yet been fully elucidated. It is currently considered to be different from the single substance transport abnormality, that is, not due to a specific carrier or receptor defect. There are two main mechanisms:
1. There is a leak in the tubular membrane of the renal tubule, and the evidence that the solute can not be fully reabsorbed is that the renal glucosuria belongs to the type A, indicating that the glucose transport reabsorption site is less, and the phosphate and bicarbonate are reduced in the filtration load. There are still losses, which indicates that their excretion is through the leakage of the renal tubules.
2. Insufficient energy metabolism in the renal tubules, the energy produced is difficult to support normal transport, some poisons or drug poisoning and genetic metabolic diseases cause some metabolites to accumulate in the renal tubules, affecting the intracellular oxidative phosphorylation process, ATP production Insufficient, there is not enough energy to support the renal tubule transport substance, no matter what mechanism can eventually lead to a variety of substance transport abnormalities, Fanconi syndrome is a multi-transfer defect in the proximal convoluted tubule, including amino acids, glucose, sodium, potassium, calcium, Phosphorus, sodium bicarbonate, uric acid and protein, the primary proximal tubules are swan neck-like deformation.
Prevention
Fanconi syndrome prevention
The disease is a hereditary disease, there is no specific preventive measures for its onset, patients with secondary or confirmed diagnosis should be actively symptomatic treatment to prevent complications and delay renal failure. Life restraint pays attention to rest, work and rest, life is orderly, and maintaining an optimistic, positive and upward attitude towards life is of great help in preventing diseases. Do the regularity of tea and rice, live daily, not overworked, open-minded, and develop good habits.
Complication
Fanconi syndrome complications Complications hypokalemia kidney stones
Common complications are renal tubular acidosis, hypokalemia, secondary hyperparathyroidism, renal osteodystrophy, bone deformity, osteomalacia, kidney stones and so on.
Symptom
Fanconi syndrome symptoms common symptoms saddle nose hypocalcemia metabolic acidosis hypophosphatemia constipation proteinuria hypokalemia
The disease is rare, more than adult symptoms, renal glucosuria, multiple amino aciduria, hypercalciuria, renal loss of sodium, hypophosphatemia, proximal renal tubular acidosis, hypouricemia, renal tubules Proteinuria, hypokalemia (muscle weakness, soft palate, periodic paralysis, etc.), hypocalcemia (hand and foot spasm), etc., long-term hypocalcemia, can cause secondary hyperparathyroidism, kidney Osteopathic disease, the most prominent clinical manifestations of this disease are vitamin D deficiency in children and osteomalacia in adults. The clinical manifestations of secondary Fanconi syndrome are basically the same as those of primary ones, but they may have their roots. The clinical manifestations of the disease, the clinical manifestations of this syndrome are complex, according to their clinical types are as follows:
1. The primary Fanconi syndrome consists of three types:
(1) Adult Fanconi syndrome: onset after 10 to 20 years of age, there are a variety of renal tubular dysfunction, such as full amino acid urine, diabetes, phosphate urine, high blood chlorine acidosis, hypokalemia, etc. The symptoms are rickets, and in a few cases there may be renal failure in the late stages of ketosis.
(2) infant-type Fanconi syndrome: more than 6 to 12 months of onset, polyuria, polydipsia, dehydration, constipation, weakness, refusal to eat, fever, growth retardation, renal amino acid urine, anti-vitamin D rickets and serious Malnutrition, laboratory tests showed hypokalemia, hypophosphatemia, hypocalcemia and alkaline phosphatase, high chloride metabolic acidosis, urinary titratable acid and NH4 can be reduced, urine sugar or 4 ~ 5g / d, normal blood sugar, acute onset of poor prognosis, often died of uremia, chronic onset more than 2 years old, the symptoms are mild, prominent manifestations of gnomes and / or anti-vitamin D rickets.
(3) Idiopathic brush-like missing Fanconi syndrome: In 1984, Manz et al first reported that a child with a complete loss of the proximal convoluted brush border caused Fanconi syndrome, because glucose and various amino acid carrier systems were completely lost. Therefore, the clearance rate of these substances is close to the glomerular filtration rate.
2. Secondary Fanconi syndrome has multiple primary diseases, and the causes of different causes are different.
(1) Cystine accumulation disease: This disease is also known as Lignac-Fanconi syndrome, which is caused by cystine deposition in cell lysosomes and is expressed as Fanconi syndrome. In normal human cells, lysosomes are the sites of intracellular protein degradation. The degradation of intracellular proteins produces amino acids that are re-utilized by the lysosomal membrane transfusion system, and the cystine carrier in the lysosome is defective, causing cystine to accumulate in the lysosome, thereby destroying The integrity of the lysosome, and can cause the destructive lysosomal enzyme to leak into the cytoplasm, affecting the function, the disease is different from cystineuria, the latter is the renal tubular epithelial transport cystine disorder, only Causing cystine urine, the former causes cystine accumulation in many organ cells, and the kidney is one of the main affected organs.
The Fanconi syndrome caused by cystine accumulation disease is different from Fanconi syndrome caused by other causes. It is often characterized by loss of potassium, dehydration, polydipsia, and osmotic diuresis. It can be divided into 3 types clinically:
1 Infant or nephrotic type: Cystine is deposited in various tissue lysosomes, which may be 80 times larger than normal in white blood cells, and the renal medulla may be nearly 100 times more likely to have various symptoms due to tubular damage. Onset in about 6 months, polyuria, polydipsia, constipation, polydipsia, vomiting, refusal to eat, weight loss, developmental disorders, due to dehydration and repeated fever, vitamin D deficiency and dwarfism can occur, due to cornea, conjunctival cyst Lysine and photophobia, pigmentation around the fundus, can cause peripheral retinopathy, in addition to thyroid dysfunction, diabetes, splenomegaly, cerebral edema, myopathy, renal tubular dysfunction is characterized by renal dysfunction Hydrogen ion excretion dysfunction, and the urine can not be acidified to below pH 5.5, showing renal tubular acidosis.
2 child type or intermediate type: about 10 years old, slow progress, bone disease is not serious, no dwarfism, tissue cystine content is much lower than infant type, the cysteine content in leukocytes is 30 times normal, also Can be expressed as renal lesions, and even developed into uremia, skeletal malformations, photophobia, retinopathy, cystine-induced splenomegaly can also occur, Fanconi syndrome is not obvious.
3 adult type: no kidney disease, mainly other organ dysfunction, adult type can be divided into acute and chronic, the former is similar to the infant type, the latter is similar to the child type.
Diagnosis by crystallization analysis of bone marrow, white blood cells, rectal mucosa or slit lamp to detect corneal cystine crystals. Infant type is caused by hunger-feeding causing hunger ketosis plus renal tubular glucosuria, which is easily misdiagnosed as childhood diabetes. Be vigilant.
(2) Lowe syndrome: This syndrome was first reported in Lowe in 1952, also known as ocular-brain-renal syndrome. The clinical manifestations are:
1 eye symptoms: congenital cataract (bilateral) with congenital glaucoma (bull eye), severe visual impairment, nystagmus and photophobia.
2 brain symptoms: severe mental retardation, low muscle tone, sputum reflexes weakened or disappeared, children often crying and screaming.
3 renal tubular dysfunction: multiple groups of amino acid urine, phosphate urine, bicarbonate urine, poor uric acid function, urinary discharge of lysine, tyrosine, and renal tubular proteinuria, can occur later Chronic renal insufficiency can be divided into three stages according to natural development: in infancy, mainly eye and brain symptoms, manifested as head deformity (long head, high forehead, saddle nose, sorghum bow, etc.); Complete Fanconi syndrome, renal tubular proteinuria, severe phosphate urine can cause anti-vitamin D rickets or osteoporosis, generally have lighter or no diabetes, potassium loss and polyuria, often umbilical hernia, cryptorchidism Malformation, as well as special finger arthritis, adulthood, renal tubular symptoms subsided, renal insufficiency or malnutrition, often accompanied by pneumonia and death, this syndrome is mainly symptomatic treatment, such as correcting renal tubular acidosis, anti- Treatment of vitamin D rickets, no cure, poor prognosis, often died in childhood due to secondary infection or renal failure.
(3) Wilson's disease (Wilson's disease): This disease is a rare recessive hereditary metabolic disease, because the content of ceruloplasmin is decreased, the activity of copper oxidase is reduced, and the intestinal tract absorbs a large amount of copper. Copper deposits in the liver, brain, cornea, and renal tubules cause corresponding symptoms. Copper deposits in the brain and liver cause extrapyramidal symptoms and cirrhosis. Copper deposits in the cornea to cause the Kayser-Fleischer ring, and copper deposits in the proximal tubules and Far-end renal tubules cause Fanconi syndrome, which may be associated with loss of bicarbonate and renal calcinosis with hypercalciuria, renal tubular acidosis, renal calcification, and kidney stones.
The disease can be treated with penicillamine, which promotes the excretion of copper from the urine but will recur after discontinuation. Other treatments such as diphenylpropanol (BAL) can increase copper excretion. Oral sodium sulfide can improve nervous system and liver symptoms, but renal tubules. There is no improvement in lesions, and bone alcohol can treat bone lesions.
(4) Hereditary fructose intolerance: This disease is an autosomal recessive enzyme deficiency disease, due to lack of 1-phosphorylaldose aldolase or 1,6-diphosphate fructose aldolase activity in liver and kidney tissues Decreased, so that fructose 1-phosphate can not be lysed and accumulated in the cells to produce lesions, and at the same time, it can affect the energy metabolism of cells due to the inability to produce ATP. If the patient is infused with fructose, it can produce Fanconi syndrome combined with tubular dysfunction, if the fructose is eliminated The renal tubular function is normal, the pathogenesis of this disease may be due to the lack of aldolase degradation of 1-phosphate fructose in renal cortical cells, decreased phosphate in tubular epithelial cells, and reduced inhibition of adenosine deaminase (ADA) And even the ADA activity is enhanced, the adenosine is deaminated to produce inosine, which produces hypoxanthine by nucleoside phosphorylase, and then produces uric acid by xanthine oxidase, thus producing hypophosphatemia. In addition, because phosphorus can increase the rate of ATP production in the renal cortex, and convert fructose into -glycerophosphate, when hypophosphatemia, ATP production is reduced, which also affects the energy supply. Thus, it is seen that 1-phosphate fructose is not Metabolites, it does not inhibit the enzyme system, but since the consumption of ATP empty phosphorus and other high-energy phosphate compound is greatly limited in certain positions generating tubular cells.
Infants are asymptomatic due to ingestion of lactose, acute onset when eating fructose or fruit, vomiting, diarrhea, hypoglycemia and hyperuricemia 20 to 40 minutes after ingestion, acute Fanconi syndrome, lactic acidosis, biliary after 2 hours Redness, large liver, timely withdrawal of fructose, treatment of hypoglycemia, the condition may slowly reverse, otherwise it may directly threaten life.
(5) Tyrosinemia: This disease is caused by the lack of hydroxylphenyl puruvic acid oxidase in patients with abnormal tyrosine metabolism, which can cause Fanconi syndrome, which is characterized by bloody cheese. Amino acid, phenylalanine, methionine, alanine increased significantly, other amino acids increased little, and tyrosine, phenylalanine, methionine and p-hydroxyphenylpyruvate, p-hydroxyphenylacetic acid phenolic acid were excreted in the urine. Metabolites also increase, clinically, the disease is divided into two types: type I tyrosinemia is temporary high tyrosinemia, if tyrosine is administered, liver and kidney function damage will occur, and long-term persistence will be renal cortex. Renal tubule degeneration, cirrhosis with portal hypertension and ascites, vitamin D deficiency in some cases, cataract formation or hypoglycemia due to islet cell hypertrophy, type II is characterized by persistent high tyrosinemia, The condition continued to develop, with severe mental retardation, abnormal skin, cataract, slow growth, and no obvious liver and kidney damage, and its p-hydroxyphenylpyruvate oxidase activity was normal. Dietary therapy (such as low tyrosine, low phenylalanine diet) can improve the condition of type II patients, and can reduce tubular damage in type I patients, but is not effective for severe liver damage.
(6) Cytochrome c oxidase deficiency: This disease can cause Fanconi syndrome, which is caused by the lack of the enzyme in the mitochondria of renal tubular epithelial cells, which causes the ATP synthesis and oxidative phosphorylation process in the electron transport chain. After 11 to 13 weeks of onset, mainly manifested as mitochondrial myopathy, lactic acidosis and renal diabetes, amino aciduria, phosphate urine and other renal tubular dysfunction.
(7) Fanconi syndrome caused by multiple myeloma: multiple myeloma may be associated with renal amyloidosis or light chain protein ( or ) caused by tubular damage resulting in non-genetic secondary Fanconi syndrome, clinical It is characterized by bone pain, muscle weakness, fatigue, anemia, osteomalacia, pseudo-fracture, etc., and has symptoms of renal tubular insufficiency such as glucoseuria, amino aciduria, phosphate urine, renal diabetes insipidus, and renal tubular acidosis. Among them, Fanconi syndrome is a symptom associated with multiple myeloma.
(8) Fanconi syndrome caused by toxic substances: toxic substances can cause secondary Fanconi syndrome, such as expired tetracycline, its degradation products have tubular toxicity, its clinical features are myopathy, dizziness, acidosis, polyuria, low Potassiumemia may recover after stopping the drug, but some courses last for more than 2 years.
Examine
Examination of Fanconi syndrome
Urine check
The urine is alkaline, the specific gravity is low, urine protein, urine sugar positive, urinary calcium, potassium, phosphorus, uric acid increase, and renal all-amino acid urine.
2. Blood test
Blood calcium, phosphorus, potassium, uric acid, carbon dioxide binding, blood chlorine increased, blood alkaline phosphatase increased.
3. Regular X-ray examination
Osteoporosis, skeletal deformities, and urinary calculi can be found.
4. Other inspections
Fanconi syndrome caused by cystine accumulation disease, cystine crystals were examined in the cornea by crystallization analysis in bone marrow slices, white blood cells, rectal mucosa or slit lamp.
Diagnosis
Diagnosis and identification of Fanconi syndrome
diagnosis
According to the patient's cause of proximal tubular damage, there is laboratory evidence of proximal renal tubular damage, especially amino aciduria, phosphate urine and glucoseuria, combined with the characteristics of each disease to establish a diagnosis.
Differential diagnosis
1. Infant Fanconi syndrome differential diagnosis should pay attention to other causes of renal tubular acidosis, muscle weakness or gait instability similar to neurological disease or primary myopathy, also similar to Fanconi syndrome infant type Should pay attention to the distinction.
2. Adults with other metabolic bone diseases caused by osteoporosis with myopathy are similar to Fanconi syndrome, uremia patients may have glucose urine or amino acid urine without hypophosphatemia, Wilson disease will also be confused with sports diseases In short, complex renal tubules must be found in their primary disease by excreting too much solute.
