Renal aminoaciduria in children
Introduction
Introduction to Pediatric Renal Amino Aciduria Hyperaminoaciduria is a type of metabolic disease characterized by excessive amino acid excretion in the urine. It can be divided into pre-renal, renal and mixed. The treatment effects of various types of high amino aciduria vary widely, and some can achieve good results by strictly controlling the intake of the corresponding amino acids in the diet or supplementing certain vitamins. Some even take various measures to make plasma amino acid levels close to normal, and can not improve clinical symptoms. Renal amino aciduria is a proximal renal tubular reabsorption amino acid disorder, which causes a large amount of amino acids to be excreted from the urine. The amino acids excreted from the urine are mainly glycine, taurine, methyl histidine, etc. In addition, serine and threonine , leucine, phenylalanine, etc. may also be discharged in small amounts. basic knowledge The proportion of illness: 0.001% Susceptible people: children Mode of infection: non-infectious Complications: hypocalcemia, hyperuricemia, acute cerebellar ataxia in children
Cause
Pediatric renal amino aciduria etiology
(1) The cause of the disease is a family hereditary disease, which is an autosomal recessive hereditary disease. The influencing factors include age, gender, diet, physiological changes, heredity, etiology and classification:
1. Physiological amino acid urine is caused by physiological changes.
2. Pathological amino acid urine caused by disease caused by amino acid urine:
(1) "prerenal" amino acid urine:
1 "spill" amino acid urine: such as phenylketonuria, maple succulent, is caused by a certain amino acid metabolism defect.
2 "competitive" amino acid urine: such as hyperprolineemia, etc., caused by competition in the renal tubules with the amino acid of the same transport system.
(2) "Kidney" amino acid urine: caused by a defect in the transport of proximal convoluted tubules:
1 a single group of amino acid transport system defects: that is, the proximal tubules are defective in the transport system of a group of amino acids, and the group of amino acids are excreted from the urine, including lysine, arginine, ornithine, cystine, and guanidine. Amino acid, hydroxyproline, glycine, aspartic acid, glutamic acid, and the like.
2 groups of amino acid transport system defects: due to multiple functional defects in the proximal curved tube, a variety of amino acid urine, accompanied by diabetes, high phosphate urine, uric acid dysfunction, such as Fanconi syndrome, Lowe syndrome Wait.
(B) the pathogenesis of urinary amino acid total excretion increased or a significant increase in individual amino acid excretion, known as amino acid urine, amino acids are an important nutrient in the human body, most of the amino acids in the body can be used to synthesize protein, plasma amino acids can be free It is filtered out into the original urine through the glomerulus, and most of it can be reabsorbed back to the blood through the proximal tubule. When the renal tubular function is reduced, the amino acid excretion in the urine increases, causing a lot of amino acid urine. Some are genetic diseases, but also caused by kidney damage caused by drugs or poisons. Pathological amino acid urine can be divided into spilled amino acid urine and renal amino acid urine. The former refers to the increase of blood amino acid, which exceeds the reabsorption capacity of renal tubules; It is due to congenital tubular disease, such as Fanconi syndrome, hepatolenticular lesions, etc. Renal amino aciduria is a hereditary disease, including basic amino aciduria (cystineuria), neutral amino aciduria (Hartnup disease), Other amino acid urine, etc., is caused by the defect of proximal convoluted tubule transport. Basic amino acid urine (cystineuria) is the most common amino acid urine. Forming cystine stones, providing naked nuclei for oxalate stone formation, neutral amino aciduria (Hartnup disease) mostly in children with onset or aggravation, other iminoglycine urine, simple cystine urine, simple glycine urine and two Carboxy amino acid urine is less common.
Prevention
Pediatric renal amino aciduria prevention
Renal amino aciduria is a hereditary disease. It is mainly used to prevent urinary calculi caused by cystineuria. There are two basic points: one is to reduce the concentration of cystine in urine, and the other is to increase the solubility of cystine, such as patient urine. The excretion of cystine is less, and it belongs to calculus-free cystineuria. It can be treated without special treatment, dynamic observation, regular review, and some patients are given D on the basis of hydrated urine and alkalized urine. - Penicillamine or -mercaptopropionyl pentyne glycerol, can effectively inhibit the growth of urinary calculi; it can also be found that after the above treatment, the concentration of urinary cystine is controlled at 138-326 mg/gCr, and the stone gradually disappears, but The drug has major side effects, 30% have significant side effects with tiopronin, and 85.7% with D-penicillamine have side effects. Chow et al have studied 16 patients who are using D-penicillamine or alpha. - In the case of failure of decylpropionyl pentyne glycerol, captopril was used, and the results showed that both D-penicillamine and -mercaptopropionyl glycerol glycerin failed to treat hydrated urine and alkalized urine. Patients have a lower chance of producing stones, and captopril has the same Effect, but the effect seems to be as good as the first two, and they no additive effect.
Complication
Pediatric renal amino acid urinary complications Complications hypocalcemia, hyperuricemia, acute cerebellar ataxia in children
Can be complicated by urinary calculi, mental retardation, hypocalcemia, hyperuricemia, muscular atrophy, cerebellar ataxia and so on.
Symptom
Pediatric renal amino acid urinary symptoms Common symptoms Urinary calculi mental retardation Hematuria extrarenal obstruction for half a year or after 1 year old... Dicarboxy amino acid urinary dibasic amino aciduria hyperuricemia cerebellar ataxia dystrophy
1. The commonality of common amino acid urinary clinical manifestations is growth and development disorders. In addition to short stature, there are many degrees of mental retardation.
2. Characteristic performance varies depending on the type of amino acid urine:
(1) cystine urine (alkaline amino acid urine): the disease is the most common amino acid urine, easy to form cystine stones, providing bare nuclei for the formation of oxalate stones.
1 specific renal amino acid urine: there are a large amount of cystine and three dibasic amino acids in the urine, and the excretion of urinary cystine can be seen in the concentrated urine sediment, which is the diagnosis of this disease. It is of great value. The homozygous urinary cytosine, lysine, arginine and ornithine are positive in the three subtypes. The heterozygous urinary cystine and lysine in patients with type II and III are also positive. .
2 cystine stones: urinary calculi are often an important clue for patients to obtain diagnosis, often causing repeated renal colic, hematuria, obstruction and secondary infection, etc., stones and sodium cyanide sodium positive reaction, can be used as a screening diagnosis Tests, such as urinary cystine excretion is less, and its concentration is maintained below saturation, it is called acalculous cystinuria, Stoller et al. through a survey of a family member of the patient, found in In the same diet for more than 72h, the average urinary cystine concentration was 496mg/gCr in 3 patients with stones; the average urinary cystine concentration was 364mg/gCr in 6 patients with an average age of 50 years but no urinary calculi. Another 34 members had a slight increase in urinary cystine concentration (mean 151 mg/gCr). Only 2 members had an average age of 44 years, but the urinary cystine concentration was normal. This study suggests that each case is severe cystine. In the family of patients with urinary tract, there may be several patients with no calculi with cystine urinary dysfunction.
3 short body, mental retardation: may be related to the loss of a large number of amino acids (especially lysine).
4 pyrrolidine and acridine urine.
5 other: a small number of patients often associated with hereditary hypocalcemia, hereditary pancreatitis, hyperuricemia and muscle atrophy.
(2) Tryptophan urinary (neutral amino acid urinary): due to insufficient formation of niacinamine, causing pellagra-like skin damage and neurological symptoms, such as Hartnup disease, the disease is mostly morbid or aggravated in children, most patients appear in childhood Symptoms, intermittent, spontaneous remission after adulthood, some patients to adulthood.
1 short stature: It is generally believed that young people may have short stature, which is caused by a large loss of the above amino acids from the urine and feces, causing nutritional disorders, but according to the long-term dynamic observation of 15 children in Australia by Wilcken et al. The disease has little effect on the growth and development of children, and the height is only slightly affected, and the mental development is normal.
2 skin damage: light-sensitive psoriasis-like rash, in the exposed parts of the body, the skin rash after sun exposure, Mori et al reported a 37-year-old adult onset, clinical manifestations only neuropsychiatric symptoms, no skin changes.
3 neuropsychiatric symptoms: severe cases may have paroxysmal cerebellar ataxia, occasional psychiatric symptoms, can spontaneously relieve within a few weeks, excessive activity and breastfeeding can aggravate skin and nervous system symptoms, the disease has a good prognosis.
(3) tyrosine urine: can produce paroxysmal cerebellar ataxia and psychiatric symptoms, according to the above clinical history, family history and a large amount of cystine in the urine can be diagnosed, quantitative analysis of urine chromatography for diagnosis and classification Help.
Examine
Pediatric renal amino acid urine test
1. Urine test urine contains a lot of cystine, lysine, arginine and ornithine, urinary cystine test methods are as follows:
(1) urinary cystine crystal examination: urinary cystine excretion is larger, cystine crystals can be seen in concentrated urine sediment, which is of great value for the diagnosis of this disease, taking morning urine for centrifugation, Under the light microscope, a hexagonal flat crystal similar to the benzene ring type can be seen, and the crystallization shows that the concentration of urinary cystine exceeds 200-250 mg/L.
(2) Cyanide nitroprusside test: The stone is positively reacted with sodium cyanide cyanide. It can be used as a screening diagnostic test. The stone is ground into a powder, put a little in the test tube, add 1 drop of concentrated ammonia water, then add 1 5% sodium cyanide was added, and after 5 minutes, 3 drops of 5% sodium nitroprusside were added.
(3) Quantitative measurement by urine chromatography: it is helpful for confirmation and typing.
(4) pyrrolidine and acridine urine: due to the absorption of these amino acids by the jejunum, a large amount of lysine and ornithine are degraded in the intestine to produce cadaverine and putrescine, which are reduced to pyrrolidine and acridine from the urine after absorption. cause.
(5) urine routine examination: urinary tract stones often cause repeated hematuria, secondary white blood cells increase infection.
2. A small number of blood tests can be combined with hyperuricemia, hypocalcemia, and the like.
3. Fecal examination due to poor absorption of amino acids in the jejunum, a large number of amino acids are lost from the feces, abdominal plain film examination shows that the stones are lightly shadowed, angiography, B-ultrasound can also find stones, EEG examination and brain CT examination can find abnormalities, Authors of severe encephalopathy may have diffuse brain atrophy. Tahmoush et al found that children with cerebellar ataxia have extensive neuronal loss in the cerebral cortex and reduced cerebellar Purkinje cells.
Diagnosis
Diagnosis and diagnosis of renal adiponectin in children
Depending on laboratory tests and clinical manifestations, it is easy to identify physiological or pathological amino acid urine. According to urinary cystine crystal examination, it helps to distinguish cystineuria from other amino aciduria, combined with clinical specific characteristics such as neuropsychiatry. Symptoms, symptoms of skin damage, contribute to the identification of Hartnup's disease.
