Pediatric renal aminoaciduria

　　Pediatric renal aminoaciduria is a familial hereditary disease, belonging to autosomal recessive hereditary diseases. Influencing factors include age, gender, diet, physiological changes, and genetics, with physiological aminoaciduria caused by physiological changes. Pathological aminoaciduria caused by diseases leading to aminoaciduria includes:

　　1, 'Pre-renal' amino aciduria:'Overflow' amino aciduria includes phenylketonuria, maple syrup urine disease, which is caused by a defect in the metabolism of certain amino acids. 'Competitive' amino aciduria includes hyperprolinemia, etc., which is caused by competition with amino acids in the same transport system in the renal tubules.

　　2, 'Renal' amino aciduria:It is caused by a defect in the transport of proximal tubules. Defect in the single amino acid transport system: that is, the transport system of a group of amino acids in the proximal renal tubules is defective, causing the excretion of amino acids from the urine, including lysine, arginine, ornithine, cystine, proline, hydroxyproline, glycine, aspartic acid, glutamic acid, etc. Defect in the multi-group amino acid transport system: due to multiple functional defects in the proximal loop tube, there are multiple amino aciduria, accompanied by diabetes, hyperphosphatemia, and uric acidification dysfunction, such as Fanconi syndrome, Lowe syndrome, etc.

　　An increase in the total excretion of amino acids in urine or significant increase in the excretion of individual amino acids is called amino aciduria. Amino acids are an important nutrient in the human body, and most of the amino acids in the body can be used to synthesize proteins. Amino acids in plasma can be freely filtered into the urine by the glomerulus, and most of them can be reabsorbed back into the blood by the proximal tubules. When the function of the renal tubules deteriorates, the excretion of amino acids in urine increases. There are many causes of amino aciduria, most of which are genetic diseases, and some are caused by kidney damage due to drugs or toxins. Pathological amino aciduria can be divided into overflow amino aciduria and renal amino aciduria. The former refers to an increase in blood amino acids that exceeds the reabsorption capacity of the renal tubules; the latter is due to congenital renal tubular lesions, such as Fanconi syndrome, hepatolenticular degeneration, etc. Renal amino aciduria is a genetic disease, including alkaline amino aciduria (cystinuria), neutral amino aciduria (Hartnup disease), and other amino acidurias, which are caused by defects in the transport of proximal tubules. Alkaline amino aciduria (cystinuria) is the most common type of amino aciduria, which is prone to form cystine stones and provide a nucleus for the formation of oxalate stones. Neutral amino aciduria (Hartnup disease) often occurs in children or worsens. Other sub-aminosugary amino aciduria, simple cystinuria, simple glycineuria, and dicarboxylic amino aciduria are less common.

　　In addition to general symptoms, pediatric renal amino aciduria can also cause other diseases. This disease can be complicated with urinary tract stones, intellectual disability, hypocalcemia, hyperuricemia, muscle atrophy, and cerebellar ataxia, etc.

　　The common characteristics of various amino aciduria clinical manifestations are growth and development disorders, in addition to short stature, there are varying degrees of intellectual development delay. The characteristic manifestations vary with the type of amino aciduria, cystinuria (alkaline amino aciduria) is the most common type of amino aciduria, which is prone to form cystine stones and provide a nucleus for the formation of oxalate stones.

　　1. Specific renal aminoaciduria is characterized by a large amount of cystine and three diamino acids in urine. For individuals with large cystine excretion, cystine crystals can be observed in the concentrated urine sediment, which is of great value for the diagnosis of this disease. Cystine, lysine, arginine, and ornithine are all positive in the homozygous urine of the three subtypes, and cystine and lysine are also positive in the heterozygous urine of patients with type II and III.

　　2. In cystine stones, urinary tract stones are often an important clue for diagnosis in patients, often causing recurrent renal colic, hematuria, obstruction, and secondary infection. The stones give a positive reaction with sodium nitroprusside, which can be used as a screening diagnostic test. If the excretion of cystine in urine is low and its concentration remains below saturation, it is called 'non-stone cystinuria' (acalculous cystinuria).

　　3. Short stature and delayed intellectual development: This may be related to the loss of a large amount of amino acids (especially lysine).

　　4. Pyrrolidine and purineuria.

　　5. A small number of patients often have hereditary hypocalcemia, hereditary pancreatitis, hyperuricemia, and muscle atrophy, etc.

　　Tyrosinuria can cause episodic cerebellar ataxia and psychiatric symptoms. Diagnosis can be made based on the above clinical history, family history, and the presence of a large amount of cystine in urine.

　　Renal aminoaciduria is a genetic disease, and the clinical prevention mainly focuses on preventing uric acid stones caused by cystinuria. The two basic points are to reduce the concentration of cystine in urine and to increase the solubility of cystine. If the patient has a low excretion of cystine in urine, it belongs to 'non-stone cystinuria' and may not require special treatment. Dynamic observation and regular re-examination can be performed.

　　Based on the principles of hydrating urine and alkalinizing urine, some patients may be given D-penicillamine or alpha-mercaptoacetyl pentane glycerol, which can effectively inhibit the growth of urinary tract stones; it can also be found that after the above treatment, the cystine concentration in urine is controlled at 138-326mg/gCr, and the stones gradually disappear. However, this drug has significant side effects, 30% of those who use Thiopurine have significant side effects, and 85.7% of those who use D-penicillamine experience side effects. Chow et al. conducted a study on 16 patients, who used Captopril after failing to use D-penicillamine or alpha-mercaptoacetyl pentane glycerol. The results showed that both D-penicillamine and alpha-mercaptoacetyl pentane glycerol can reduce the risk of stone formation in patients whose treatment with hydrating urine and alkalinizing urine has failed, and Captopril also has the same effect, but the efficacy seems to be less than the former two, and there is no additive effect.

　　The main clinical examination methods for pediatric renal aminoaciduria include urine examination, blood examination, and fecal examination, as follows:

　　1. Urine examination

　　1. Cystine crystalluria examination: For individuals with large cystine excretion, cystine crystals can be observed in the concentrated urine sediment, which is of great value for the diagnosis of this disease. Centrifugation of morning urine can reveal hexagonal flat crystals similar to benzene rings under a light microscope, and the appearance of crystals often indicates that the cystine concentration in urine exceeds 200-250mg/L.

　　2. Cyanide nitrosyl salt test: Stones react positively with sodium nitrosocyanide, which can be used as a screening diagnostic test. The stones are ground into powder, a small amount is placed in a test tube, and one drop of concentrated ammonia water is added, followed by one drop of 5% sodium cyanide. After 5 minutes, add 3 drops of 5% nitrosyl sodium.

　　3. Urinary chromatographic quantitative determination: It is helpful for confirmation and typing.

　　4. Pyrrolidine and pyrimidineuria: Due to poor absorption of these amino acids by the jejunum, large amounts of lysine and ornithine are degraded in the intestines to produce cadaverine and putrescine, which are absorbed and then reduced to pyrrolidine and pyrimidine and excreted in urine.

　　5. Urinalysis: Aminoaciduria urinary tract stones often cause recurrent hematuria, and when secondary infection occurs, white blood cell count increases.

　　II. Blood test

　　A few cases can be accompanied by hyperuricemia, hypocalcemia, and other conditions.

　　III. Fecal examination

　　Due to poor absorption of amino acids by the jejunum, amino acids are lost in large quantities in feces. Abdominal X-ray examination shows thin shadows of stones, contrast and B-ultrasound examination can also find stones, electroencephalogram examination and brain CT examination can find abnormalities. Severe encephalopathy can have diffuse brain atrophy. Tahmoush et al. found that children with cerebellar ataxia have widespread neuronal loss in the brain cortex and a decrease in Purkinje cells in the cerebellum.

　　In addition to general treatment methods for pediatric renal aminoaciduria, the following dietary therapy methods can also effectively improve symptoms:

　　I. Chicken essence for therapy

　　1. Chicken essence is rich in nutrients, containing not only monosodium glutamate but also various amino acids, proteins, vitamins, and other nutrients, which have higher nutritional value than monosodium glutamate.

　　2. It can supplement human amino acids, which is beneficial to enhance and maintain brain function.

　　3. Due to its excellent flavor, it can increase appetite.

　　II. Oyster sauce for therapy

　　1. Oyster sauce is rich in trace elements and various amino acids, which can be used to supplement various amino acids and trace elements. Among them, it is rich in zinc, which is the first choice of dietary seasoning for people with zinc deficiency.

　　2. Oyster sauce contains more than 22 types of amino acids, and the content of various amino acids is coordinated and balanced. Among them, the content of glutamic acid is half of the total amount. It, together with nucleic acids, constitutes the main flavor of oyster sauce. The higher the content of both, the more delicious the taste of oyster sauce.

　　3. Oyster sauce is rich in taurine, which has various health benefits such as anticancer, antitumor, and enhancing the human immune system.

　　Since pediatric renal aminoaciduria is a genetic disease, there is no curative method yet, and symptomatic treatment is required. The main treatment methods currently are as follows:

　　I. Diet control

　　The type of aminoaciduria varies. Patients with cystinuria should be given a low methionine diet. Patients with tryptophan, phenylalanine, and tyrosine aminoaciduria should be given a high-protein diet and supplemented with niacin; however, protein should be avoided if ataxia and psychiatric symptoms occur.

　　II. Hydration of Urine

　　Increase fluid intake to maintain polyuria (including at night). Ensure that the urine volume reaches more than 4L in 24 hours, especially emphasize drinking water before going to bed at night to maintain nocturnal urine volume above 1.5L; because without drinking water for a long time at night, the urine becomes highly concentrated, which is a key factor in the formation of cystinuria urinary tract stones.

　　III. Symptomatic Treatment

　　1. Adjust pH changes. You can also use 10% potassium citrate, starting with a dose of 10ml, three times a day.

　　2. Intravenous infusion of glucose, oral antibiotics, etc.

　　IV. Drug Treatment

　　When the excretion of urinary cystine is too high (＞750mg/d or 3mmol/d), or when hydration and alkalinization of urine cannot effectively prevent urinary tract stones, consider using thiol derivatives such as D-penicillamine, thiopurine (tiopronin), alpha-mercaptoacetyl glycine (alpha-mercaptopropionylglycine), and recently, some people have tried captopril. These drugs form high-solubility disulfides with cystine, significantly reducing the concentration of free cystine in urine. However, these drugs can cause serum sickness-like reactions, transient leukopenia, proteinuria, and reversible nephrotic syndrome.

　　1. Penicillamine: It can not only reduce free cystine in urine but also prevent the formation of stones. However, this drug has significant side effects. Medications such as thiopropionic acid, glycine, glutamine, chlordiazepoxide (Librium) can be given.

　　2. N-Acetyl-D-Penicillamine: It has lower toxicity and the same effect as the previous one. Thiopurine (methylguanidine) has the same effect as penicillamine but lower toxicity.

　　3. Nicotinamide: Photosensitive dermatitis, cerebellar ataxia, and mental confusion can occur in neutral amino aciduria (Hartnup disease). Nicotinamide treatment can prevent the occurrence of pellagra and neuropsychiatric symptoms.

　　V. Kidney Stone Treatment

　　In addition to using extracorporeal lithotripsy or surgical stone removal, you can also take traditional Chinese medicine for stone expulsion. Extracorporeal shock wave therapy for cystine stones is not effective, and at this time, surgical treatment is required. Asanuma et al. reported 13 patients who received surgical treatment.