Childhood multifunctional renal tubular dysfunction syndrome

　　One, Etiology

　　The classification of Fanconi syndrome is currently divided into 3 categories:

　　1. Primary:

　　(1) Familial genetic (AD, ARTXLR).

　　(2) Sporadic.

　　2. Secondary:

　　Secondary Fanconi syndrome is most common in childhood, seen in glycogen storage disease, galactosemia, liver-nucleus degeneration, renal tubular acidosis, and lead poisoning, etc. In summary, any disease that extensively affects the reabsorption function of the proximal renal tubules can cause it. Treatment should be symptomatic and target the primary disease.

　　(1) Secondary to congenital metabolic disorders: cystinosis (AR), glycogen storage disease (AR), Lowe syndrome (XLR), galactosemia (AR), hereditary fructose intolerance (AR), tyrosinemia (AR), liver-spongiform degeneration (Wilton disease) (AR).

　　(2) Acquired diseases: multiple myeloma, nephrotic syndrome, renal transplantation.

　　(3) Poisoning: heavy metals (mercury, uranium, lead, cadmium), maleic acid, cresol, expired tetracycline, methyl 3-chromone.

　　3. Proximal tubule syndrome:

　　The proximal tubule syndrome has no clinical symptoms, only mild functional abnormalities of the proximal tubules.

　　Two, Pathogenesis

　　1. The pathogenesis of the multifunctional damage of the proximal renal tubules may be related to abnormality of the composite transport system of epithelial cells, abnormal energy metabolism, or defect in concentration gradient.

　　2. Some believe that the main pathological change is the shortening of the proximal tubules and the narrowing of the connecting part with the glomerulus, leading to metabolic disorders, hypophosphatemia, and varying degrees of acidosis. Urinary concentration dysfunction and hypokalemia have also been observed, but some renal pathological examinations are normal.

　　Common complications include malnutrition, slow growth, refractory rickets, various skeletal deformities, acidosis, proteinuria, hyponatremia, hypokalemia, anemia, and multiple deformities, etc.

　　1. General manifestations: many people in a family get sick, and the disease starts 4 to 6 weeks after the baby is born, showing slow growth, weakness, poor appetite, vomiting, polyuria, and constipation is also common. Most patients are hospitalized due to malnutrition, fever, vomiting, dehydration, and acidosis. It can also be manifested as thirst, polydipsia, and polyuria.

　　2. Refractory rickets: even after treatment with the usual dose of vitamin D, older children still show active rickets, with short stature and skeletal deformities.

　　3. Mixed renal tubular acidosis manifestations.

　　4. Low molecular weight renal tubular proteinuria.

　　5. Normal blood calcium, hypophosphatemia, elevated alkaline phosphatase, hyponatremia, and hypokalemia.

　　6. Anemia and multiple deformities: congenital aplastic anemia, whose characteristics include not only a decrease in all blood cells but also multiple congenital deformities, with brown pigmentation of the skin most common, especially on the face and around the nasolabial grooves. The next is skeletal deformities, such as absence or deformity of the thumb, microcephaly, etc., and renal, heart, and other deformities may also occur.

　　7. Metabolic abnormalities: blood glucose is normal, urine sugar is positive, blood bicarbonate binding capacity decreases while urine pH is neutral or alkaline, blood amino acids are normal or increased, and urinary amino acids are increased.

　　8. Other: Primary cases are often accompanied by excessive cystine retention in the body, known as cystinosis (Lignac-Fanconis syndrome). In addition to the above symptoms, cystine is also accumulated in the conjunctiva, cornea, and other places, showing aversion to light, and there is often a preference for protein-rich foods such as meat.

　　This syndrome is mostly autosomal recessive inheritance, with a few dominant inheritance. The etiology is not yet clear. Preventive measures are the same as those for the prevention of genetic diseases. Since many people in the family often have the disease, it is necessary to strengthen the consultation work on genetic diseases.

　　Low serum bicarbonate binding capacity, which can be below 10mmol/L (10mEq/L), low blood phosphorus, normal blood calcium, elevated alkaline phosphatase, but when renal failure occurs, blood phosphorus and non-protein nitrogen increase simultaneously, blood calcium decreases, blood potassium is sometimes low, and often hyperchloremic acidosis may occur. Urine sugar increases from trace to 5mg/dl, but blood glucose is not high. The amount of urinary amino acids is significantly increased, but blood amino acids are not high. The amount of amino acids excreted in urine reaches more than ten types, and the types of amino acids 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, and the content of ammonia in urine and the titratable acidity are both low. Routine X-ray examination, B-ultrasound, color Doppler, electrocardiogram, and other examinations can find congenital heart disease, skeletal deformities, renal deformities, and other abnormalities.

　　A reasonable diet is the key for patients with childhood multifocal tubulopathy syndrome, and a low-salt diet should not be adopted for a long time. Appropriate control of sodium intake is the key. Ensure a reasonable dietary structure and rich nutrition.

　　I. Treatment

　　1. High-dose vitamin D Use high-dose vitamin D to control rickets first, 10,000 to 50,000 U per day, starting with a smaller dose and increasing as necessary. At the same time, track the blood calcium and urine calcium concentrations and be cautious of hypercalcemia. 1,25-(OH)2D3 can also partially restore the transport function of the renal tubules.

　　2. Add electrolyte solutions such as vitamin D treatment for several weeks, if no efficacy is seen, add electrolyte solutions, which can be a mixture of sodium citrate and potassium citrate (each containing 100g of sodium and potassium salts dissolved in 1L of water, with sodium and potassium contents of 2mmol/L), which is effective for alleviating hypokalemia and acidosis. The dosage of the mixture is 2ml/(kg·d), but the dose should be adjusted according to the serum bicarbonate binding capacity and blood potassium concentration. Even if there is no hypokalemia, potassium salts should be taken orally continuously, otherwise, more potassium will be lost from the kidneys when a large amount is supplemented.

　　3. Renal insufficiency Renal insufficiency often occurs in the late stage of the disease, and potassium and sodium intake should be adjusted according to the renal excretion of electrolytes.

　　4. Diuretics such as hydrochlorothiazide (dihydrochlorothiazide) can cause a decrease in extracellular volume and increase the renal threshold for bicarbonate.

　　5. Rehydration, intravenous or oral rehydration to prevent dehydration.

　　II. Prognosis

　　When this condition is appropriately treated, rickets, acidosis, and aminoaciduria can all show significant improvement, but renal failure and uremia often occur in the later stage, and the prognosis is more severe the earlier the onset age.