Fanconi syndrome

　　There are many causes of the disease, most of which are related to heredity in infants and children, and most of which are secondary to immune diseases, metal poisoning, or kidney disease. The pathogenesis has not been fully elucidated, but it can be肯定 that it is different from abnormal transport of a single substance, that is, not due to the defect of specific transporters or their receptors.

　　It may be caused by the following reasons:

　　1. Primary or hereditary.

　　2. Other genetic diseases:Such as cystinosis, Lowe (Lowe) syndrome, hepatolenticular degeneration, tryptophanemia, hereditary lactose intolerance, deficiency of pyruvate carboxylase, and others.

　　3. Abnormal proteinemia:Such as multiple myeloma, monoclonal gamma-globulin disease, and others.

　　4. Secondary:Hyperparathyroidism accompanied by chronic hypocalcemia, such as vitamin D deficiency or antagonism, vitamin D dependence, and others.

　　5. Drugs or toxins:Such as outdated tetracycline, 3-methylxanthone, streptozotocin, adhesive, gentamicin, and others.

　　6. Heavy metal poisoning:Such as aluminum, cadmium, mercury, and others.

　　7. Renal tubulointerstitial disease:Such as Sjögren's syndrome, medullary cystic disease, renal transplantation, and others.

　　8. Other diseases:Such diseases include nephrotic syndrome, amyloidosis, osteosclerosis, paroxysmal nocturnal hemoglobinuria, and others. According to Gonick's opinion, there are six possible pathogenic mechanisms for this disease, some of which have been confirmed by clinical pathology or animal experiments. Among them, the most important are the back-leakage into the lumen and the disorder of energy supply. The evidence of back-leakage is that renal glycosuria belongs to type A, and phosphates and carbonates are still lost even when the filtration load is reduced, and even show negative clearance. The disorder of energy supply is often caused by the storage of intermediate metabolic products of metal toxins or genetic metabolic diseases in the cells, which affects the generation or transmission of ATP. Regardless of which mechanism, it can lead to abnormal transport of various substances, and the clearance amount is also greater than that of abnormal transport by a single carrier.

　　Cystinosis:An autosomal recessive genetic disease, with the disease-causing gene located on the short arm of chromosome 17. The disease is caused by the deposition of cystine in lysosomes. In normal individuals, intracellular proteins are degraded in lysosomes, and amino acids are transported into the cytoplasm through the lysosomal membrane transport system for reuse. This disease is caused by a defect in the lysosomal cystine transporter, leading to the accumulation of cystine in lysosomes, thus destroying the integrity of lysosomes and allowing lysosomal enzymes to leak into the cytoplasm, resulting in impaired function. According to the course of the disease and the content of intracellular cystine, cystinosis can be divided into 3 types:

　　1. Benign or adult cystinosis:Cystine crystals exist only in the cornea and bone marrow, with mild elevation of intracellular cystine and no involvement of the kidneys.

　　2. Infantile or nephrotic cystinosis:It is the most common type, with significantly elevated intracellular cystine levels. Kidney involvement occurs in infancy (usually at 7-12 months of age), manifested as Fanconi syndrome, rickets, and growth retardation. Renal calcinosis is common, but kidney stones are rarely developed. It usually progresses to uremia before puberty. Photophobia is a common symptom in children, often gradually worsening, which can lead to visual impairment and blindness. The diagnosis is strongly supported by the presence of crystals in the cornea under a slit lamp. Biopsy pathology shows cystine crystals in renal tubules and intestinal epithelial cells, and birefringent microscopy shows refractive crystals. Electron microscopy shows intracellular cystine crystals, leading to the unique 'dark cells' of the disease.

　　1. Sporadic Fanconi syndrome (infantile type):

　　1. Acute type:Characteristics include: ①Onset is more common between 6-12 months, often presenting with symptoms such as polyuria, polydipsia, dehydration, weight loss, constipation, vomiting, anorexia, weakness, and fever; ②Growth retardation, developmental disorders, and may have rickets due to resistance to vitamin D and severe malnutrition; ③Renal aminoaciduria is a necessary phenomenon, with normal plasma amino acid concentration; ④Laboratory findings often show hypokalemia, hypophosphatemia, hypocalcemia, and elevated alkaline phosphatase, metabolic acidosis with hyperchlorhydria, decreased titratable acid and NH4+, and微量urine sugar or 4-5g/d, normal blood glucose; ⑤Prognosis is poor, often leading to uremia, acidosis, or secondary infection.

　　2. Chronic type:Onset is later (after 2 years of age), symptoms are mild, and the prominent manifestations are dwarfism and/or rickets due to resistance to vitamin D.

　　Type 2 adult Fanconi syndrome:Characteristics include: ①Onset is slow, occurring after the age of 10-20 years; ②There are various renal tubular dysfunction, such as diabetes, aminoaciduria, phosphaturia, hypokalemia, and hyperchloraemic acidosis, rickets is the prominent manifestation, and a few cases also have ketosis; ③Renal failure may occur in the late stage.

　　Third, Idiopathic brush border deficiency Fanconi syndrome:Manz and others first reported a case of a child with this syndrome in 1984 due to the complete absence of the brush border of the proximal tubule. Because the transporters for glucose and various amino acids are completely lost, the clearance rate of these substances is close to the glomerular filtration rate (i.e., almost all are not reabsorbed), thus it is very different from the common type. The glucose reabsorption curve is not an A-type curve but similar to the O-type curve reported by Oemar et al. The clearance pattern composed of the clearance rates of various amino acids is a flat line, losing the clearance pattern of normal or common type patients, that is, the curve with higher clearance rate is larger, and the curve with lower clearance rate is smaller.

　　Fourth, Secondary Fanconi syndrome:Most cases have an underlying disease, and diagnosis is relatively easy, but the manifestations of Fanconi syndrome caused by different etiologies can be different. 1. Cystinosis, also known as cystinuria, is the most common cause of childhood Fanconi syndrome. Normally, lysosomes in cells are the site of intracellular protein degradation, and the free amino acids produced by degradation are transported into the cytoplasm through the lysosomal membrane transport system for reuse. In this disease, due to the defect in the cystine transport carrier, cystine accumulates in large quantities within the cell, affecting cell function and causing the disease. Therefore, it is different from cystinuria, which is caused by the renal tubular epithelial transport disorder of cystine, only causing cystinuria, while the former causes the accumulation of cystine in many organ cells, with the kidney being one of the main organs affected.

　　Extra-renal manifestations: ① choroidoretinitis; ② cystine crystalline deposits in the cornea, conjunctiva, iris, and lens; ③ hypothyroidism; ④ diabetes; ⑤ enlargement of the liver and spleen; ⑥ cerebral edema; ⑦ myopathy.

　　Fifth, Lowe syndrome:It is an X-linked recessive genetic disease, with the disease-causing gene located at Xq24-q26. It is more common in males. Since it was reported in 1952, there have been more than a hundred cases. Although it exists at birth, the onset of the disease is more common in infancy or later, and it can be divided into three stages according to the natural course of the disease. (1) Infancy: The main symptoms are brain and eye symptoms, manifested as congenital cataracts and glaucoma, often leading to complete blindness. Severe mental retardation, hypotonia, weakened reflexes, and cranial deformities (long head, high forehead, saddle nose, high palate, etc.). (2) Childhood: It is manifested as an incomplete Fanconi syndrome, with renal tubular proteinuria and total aminoaciduria, the latter being more obvious in lysine and tyrosine. Severe hyperphosphatemia can cause rickets or osteoporosis due to vitamin D resistance, and renal tubular acidosis may occur. In general, diabetes, potassium loss, and polyuria are mild or absent. There are often congenital malformations such as umbilical hernia and cryptorchidism, as well as special finger arthritis. (3) Adulthood: Symptoms of renal tubular disease regress, and death is often due to renal insufficiency, malnutrition, or pneumonia. A few female carriers (less than 5%) may have cataracts. There is no radical treatment other than symptomatic treatment for acidosis, bone disease, and infection.

　　Six, Deficiency of cytochrome c oxidase:To date, there have been 7 reported cases, all of which occurred between 11 and 13 weeks after birth, mainly表现为severe mitochondrial myopathy, lactic acidosis, and Fanconi syndrome. The enzyme in the patient's muscles is only 17% of that in normal people, and the enzyme in the kidneys is 38% of that in normal people.

　　Seven, Tumor-related Fanconi syndrome:In 1985, Leebey et al. reported a case of non-ossifying fibrosarcoma complicated with complete Fanconi syndrome, which completely disappeared after tumor resection.

　　Eight, Fanconi syndrome with 'nontubular proteinuria':Certain secondary Fanconi syndrome in adults may have overflow proteinuria (such as in multiple myeloma or light chain disease) or glomerular proteinuria (common in hyperglobulinemia, Sjögren's syndrome, amyloidosis, acute and chronic interstitial nephritis). These patients often have an incomplete type of Fanconi syndrome and are often complicated with nephrogenic diabetes insipidus, type I renal tubular acidosis, and acute and chronic renal insufficiency. The nephrotic syndrome complicated with Fanconi syndrome was congenital or childhood nephrotic syndrome in the early years, and in recent years, there have been reports of adult cases in China as well.

　　Nine, Hereditary Fructose Intolerance and Acute Fanconi Syndrome:This disease is an autosomal recessive enzyme deficiency disease. The incidence rate is 1:20,000. Patients almost completely lack l-phosphofructokinase, and the activity of l,6-bisphosphofructokinase is reduced by more than 50%, leading to the inability of l-phosphofructose to be cleaved and accumulating in the cells, and at the same time, it cannot produce ATP, affecting cellular energy metabolism.

　　Acute Fanconi syndrome, hypoglycemia, hyperuricemia, and hyperfibrinuria (due to the lack of phosphorus in the liver adenine nucleotides and the disorder of glycogenolysis) may occur when patients consume fructose. The onset is related to age; infants who consume lactose have no symptoms, but when fructose or fruit is added, acute onset occurs. Vomiting, diarrhea, hypoglycemia, and hyperuricemia appear 20 to 40 minutes after eating, and acute Fanconi syndrome, lactic acidosis, hyperbilirubinemia, and liver enlargement appear 2 hours later. Prompt cessation of fructose intake and treatment of hypoglycemia may slow the reversal of the condition, otherwise, it may threaten life or lead to liver and kidney dysfunction or even failure.

　　This disease is a genetic disease, and there is no effective preventive method for its onset. For secondary or diagnosed patients, active symptomatic treatment should be carried out to prevent the occurrence of complications and delay renal failure. In the late stage of onset, renal insufficiency often occurs, and the dosage of potassium and sodium should be adjusted according to the excretion of electrolytes by the kidneys.

　　When treated appropriately, rickets, acidosis, and aminoaciduria can all show significant improvement, but renal failure and uremia still occur in the end, and the earlier the onset, the more serious the prognosis.

　　Chromosome examination: can find phenomena such as clefts, breaks, and intronic replication, with an incidence rate of up to 10% to 15%. Serum carbon dioxide binding power is low, below 10mmol/L (10mEq/L). Blood phosphorus is low, blood calcium is normal, and alkaline phosphatase is increased. However, when renal failure occurs, blood phosphorus and non-protein nitrogen increase simultaneously, and blood calcium decreases. Blood potassium is sometimes low. Often, hyperchloraemic acidosis may occur. Urine sugar ranges from trace to 5mg/dl, but blood sugar is not high. Urinary amino acid levels are significantly increased, but blood amino acid levels are not high. Urinary excretion of amino acids reaches more than ten types, and the types excreted by each patient are the same before and after, but the types excreted by different patients are often different. Although the patients have acidosis, the urine pH is often relatively high. The content of ammonia in the urine and the titratable acidity are both low.

　　One, the principle of protein intake:

　　1, In the early and stable stages of kidney syndrome, high-quality protein diet should be provided, such as freshwater fish and white meat, which is helpful to alleviate hypoproteinemia and some complications caused by it.

　　2, Patients with severe Fanconi syndrome should intake less high-quality protein.

　　3, Patients with chronic renal dysfunction should have a low-protein diet.

　　Two, the principle of sodium salt intake:

　　1, When edema occurs, low-salt diet should be consumed, generally not exceeding 2g of salt per day, in order to avoid exacerbating edema. At the same time, it is forbidden to use pickled and other high-salt content seasonings or food.

　　2, Patients without edema or whose edema has subsided and whose plasma protein is close to normal can have ordinary diet and do not need to strictly limit salt.

　　Three, the principle of trace element intake:

　　Since patients with kidney syndrome lose a large amount of protein in their urine, they also lose some trace elements and hormones bound to protein, resulting in a lack of calcium, magnesium, zinc, iron, and other elements in the body. Therefore, appropriate supplementation should be given according to individual conditions, such as taking calcium tablets.

　　Four, the principle of fat intake:

　　Patients with kidney syndrome often have hyperlipidemia, which can aggravate the damage and sclerosis of the glomeruli, so patients with kidney syndrome should limit the intake of animal viscera, fatty meat, and other foods rich in cholesterol and high in fat.

　　Health care one: When kidney syndrome patients choose food, it is best to choose bitter and cold, nutritious, and easy-to-digest foods as the main food, and avoid foods that are sticky, difficult to digest, and hinder the stomach.

　　Health Tip Two: Eat less cold food, and pay attention to strengthening the spleen and stomach.

　　Health Tip Three: Do not overeat or binge, especially not to eat too much at dinner.

　　Health Tip Four: Eat meals on time, do not overeat or starve, so as not to disturb the physiological function of the spleen and stomach, and thereby worsen the condition of nephrotic syndrome.

　　Health Tip Five: Often eat diuretic and dampness-draining foods. This can strengthen the spleen and stomach, and improve the body's operational ability.

　　Health Tip Six: Proper combination of coarse and fine, dry and wet, and meat and vegetables in the diet. In terms of diet, proper adjustment helps to enhance the function of the spleen and stomach and improve the overall immunity of the body. Appropriate combinations of fine and coarse grains, and thin and thick foods should be eaten, and the arrangement of meat and vegetables should also be appropriate. For example, eat steamed buns and soy milk in the morning, rice for lunch, and congee in the evening; commonly eat green vegetables, melons, and other vegetables as the main course, supplemented with lean pork and other meat. Meat includes lean pork and duck meat.

　　First, etiology treatment:Secondary treatment focuses on treating the underlying disease, such as Wilson's disease or heavy metal poisoning to promote the excretion of toxins, and genetic metabolic diseases through dietary management to reduce the deposition of metabolic toxic substances.

　　Second, symptomatic treatment

　　1. Acidosis:Supplement alkalis according to the loss of bicarbonate, which can include bicarbonate, citrate, lactate, etc., and should be given in divided doses until the bicarbonate level in the blood returns to normal. Notes: ① Those with hypokalemia should supplement potassium concurrently, as sodium supplementation can worsen hypokalemia. ② If the dose of alkalis is too large and cannot be tolerated, hydrochlorothiazide can be added, which can reduce extracellular fluid volume and promote the reabsorption of bicarbonate, but it should be prevented that the glomerular filtration rate decreases.

　　2. Polyuria:In addition to treating the cause, such as hypokalemia, provide adequate salt-containing fluids (potassium, sodium, calcium, etc.), and in addition to taking them regularly and in proper amounts, they should also be taken as needed, and dehydration should be prevented at all costs.

　　3. Hypophosphatemia:Take neutral phosphates, and reduce the dosage if there is diarrhea or abdominal discomfort. Note that phosphorus supplementation can worsen hypocalcemia and bone disease, so vitamin D should be taken concurrently.

　　4. Hypouricemia, aminoaciduria, and proteinuria:Generally does not require treatment.

　　5. Renal Failure:Dialysis or kidney transplantation may be necessary when required.