Renal aminoaciduria

Introduction to renal amino aciduria Renal Amino Aciduria is a group of renal tubular diseases in which the proximal tubules are mainly responsible for amino acid transport disorders, resulting in the excretion of large amounts of amino acids in the urine. basic knowledge The proportion of illness: 0.015% Susceptible people: children Mode of infection: non-infectious Complications: hypocalcemia, hyperuricemia, ataxia, retinitis, pancreatitis

Renal amino aciduria

(1) Causes of the disease

This disease is due to the defect of hereditary membrane transport, which leads to an increase in the amount of amino acid excretion in the urine. The occurrence of this disease is the result of changes in the membrane carrier caused by autosomal recessive diseases. In normal, the glomerular filtered amino acids are at the proximal end. The renal tubules are almost completely reabsorbed by the specific energy transport process. When the congenital amino acid metabolism is abnormal, the amino acids that are not well metabolized increase in plasma and appear in the urine, which is caused by an increase in ultrafiltration load. Non-renal tubular transport defect, when the proximal renal tubular amino acid transport is defective, it can cause reabsorption disorder and amino acid urinary and blood amino acid levels are reduced. When an amino acid reabsorption is disordered, other amino acids of the same transport system are passed. Reabsorption can also be reduced, and lead to a wider range of amino aciduria, such as cystineuria, when an amino acid metabolism is abnormal, accumulating in the body, excessive ultrafiltration can inhibit the reabsorption of other amino acids in the same transporter, such as -prop Abnormal aminotransferase, hyperalaninemia occurs, and a large amount of taurine, isobutyric acid, -alanine in the urine, when the renal tubular epithelium is fine The brush-like or basement membrane leaks, and the reabsorbed amino acids from the cell back into the lumen cause extensive amino aciduria, such as Fanconi syndrome, lysine urine, etc., when a metabolite accumulates in the tubular epithelial cells. It can inhibit reabsorption rate, trigger amino aciduria, such as galactosemia and congenital fructose intolerance, and galactose phosphate or fructose phosphate can accumulate in renal tubular cells.

(two) pathogenesis

The amino acid content in the normal human glomerular filtrate is approximately equal to that of plasma, and most of them are reabsorbed by the proximal tubule. The amino acids excreted in the urine are mainly glycine (70-200 mg/d) and histidine (10-300 mg). /d), taurine (85 ~ 320mg / d), methyl histidine (50 ~ 210mg / d), etc., when the renal tubules interfere with the transport of certain amino acids, the amino acid urine appears.

Among a variety of amino acid transport deficiency diseases, such as cystineuria, two-base amino aciduria, Hartnup disease, iminoglycineuria, dicarboxyl amino aciduria, manifested as structurally similar amino acid transport abnormalities, suggesting membrane The presence of gene-specific membrane receptors or vectors, which affect only one amino acid transporter, indicates the presence of a substrate-specific transport system that affects the kidney and/or intestine The operating system has no effect on other tissues. The homozygous type I of this disease lacks cystine, lysine, arginine and ornithine-mediated small intestinal transit, and its heterozygotes have the normal amino acid urine excretion type. Type II homozygotes lack intestinal lysine-mediated transport, but preserve the ability to transport cystine, and their heterozygotes have a modest increase in urine excretion of four amino acids. Type III homozygotes retain these four species. Amino acid-mediated intestinal transport capacity, the heterozygous urinary lysine and cystine only slightly increased.

1. Cysturia is an autosomal recessive disorder, and its pathogenesis is the transport of cystine in the proximal tubular brush border membrane and gastrointestinal tract, and the lysine and arginine of the same transport system. Loss of ornithine site causes a large loss of the histidine urine; it is later found that the mixed disulfide formed by cysteine-homocysteine also has a reabsorption disorder in cystine. The concentration of cystine and other three kinds of amino acids in the urine of patients with urine does not increase, and the clearance rate of the amino acids in the kidney is obviously increased, and the clearance rate of cystine is more than 30 times larger than normal, and the patients with cystine urine are fed with lysine. After acid and ornithine, the blood concentration does not increase, and a large amount of these amino acids appear in the feces, and the jejunal mucosa biopsy specimen is used for active transport research, and it is also confirmed that there is a transport defect, and cysteine urine patients have monthly urine excretion of cystine. The average acidity is 3036.8 mmol (the normal maximum value is about 74.88 mmol/1g creatinine), which is obviously supersaturated, and its solubility is low. It can only dissolve l2481664 mmol/L in the urine of pH 57, so it is easy to precipitate crystals. When concentrated, the crystals are more likely to form stones and cause kidneys. Colic, urinary tract obstruction or infection.

2. Hartnup disease is caused by a proximal monoamine and a jejunal mucosa with a neutral monoamino group, a single-carboxyl amino acid transport disorder. The amino acids with transport barriers are alanine, serine, threonine, proline, leucine. , isoleucine, phenylalanine, tyrosine, tryptophan, histidine, glutamic acid and aspartic acid, among which the most important is the defect of tryptophan transport, tryptophan in urine and A large amount of feces is lost, resulting in insufficient formation of nicotinamide, causing psoriasis-like skin damage and neurological symptoms. In addition, sputum and tryptamine produced by tryptophan-like degradation in the intestinal tract, phenylethylamine produced by phenylalanine Tyramine and other amines produced by tyrosine significantly exceed the detoxification ability of the liver, causing central nervous system symptoms caused by blood circulation, manifested as paroxysmal cerebellar ataxia and psychiatric symptoms. There are two types of this disease: Intestinal dysfunction is type I; accessibility is type II.

Renal amino aciduria prevention

There are no effective preventive measures for the onset of this disease. Early diagnosis should be made for patients with existing disease, and active symptomatic treatment should be used to prevent and treat complications such as stones. This disease is a lifelong disease. Some patients are prone to urinary tract because they cannot adhere to treatment for a long time. Stones require surgical treatment if necessary.

Renal amino acid urinary complications Complications hypocalcemia, hyperuricemia, ataxia, retinitis, pancreatitis

Can be complicated by urinary stones, growth and mental retardation, hypocalcemia, hyperuricemia, muscular atrophy, cerebellar ataxia, pancreatitis, pigmentary retinitis.

Renal amino acid urinary symptoms common symptoms -amino acid urinary dibasic amino acid urinary dysfunction palm and plantar keratosis with sweating dicarboxy amino acid urinary diplopia twitching amino acid urinary intestinal transit disorder hypocalcemia gait instability

The clinical manifestations of various amino acid urins have their commonality and personality. The common clinical manifestations of various amino acid urinary tracts are growth and development disorders, short stature and varying degrees of mental retardation. The characteristic manifestations vary from amino acid to urine. .

1. Cystineuria The disease usually occurs after birth, but it is usually manifested at 20 to 30 years old and can be diagnosed. The main clinical manifestations are:

(1) Specific renal amino acid urine: There are a large amount of cystine and three kinds of dibasic amino acids (lysine, arginine and ornithine) in the urine, and the excretion of urinary cystine is larger (average daily discharge Up to 730mg) can see cystine crystals in concentrated urine sediment, three subtypes of homozygous urinary cystine, lysine, arginine and ornithine are positive, type II and III patients The heterozygous urinary cystine and lysine are also positive.

(2) Urinary tract cystine stone: due to the large amount of cystine exceeding the urinary saturation, the solubility in hard urine decreases, forming stones, cystine stones account for 1% to 2% of kidney stones, yellow brown, hard , the size can vary, the larger can be staghorn shape, often multiple, not completely X-ray, with a thin shadow, due to the inclusion of disulfide, it is less than the density of calcium stone, the stone and sodium cyanide sodium positive The reaction can be used as a screening diagnostic test. Urinary calculi are often an important clue for patients to obtain diagnosis. The commonly caused symptoms are renal colic, hematuria, urinary tract obstruction, and secondary urinary tract infection. Late stage may cause renal insufficiency. .

If the amount of urinary cystine excretion is small and its concentration is below saturation, it is called acalculous cystinuria. Studies suggest that in the family of patients with cystinuria, There are several patients with calcium-free cystineuria.

(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: 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. discharge.

(5) Others: a small number of patients can be combined with hyperuricemia, hypocalcemia, hemophilia, muscular atrophy, pancreatitis, retinitis pigmentosa and so on.

2. Two-base amino acid urinary disease This is an autosomal recessive disorder, which is the result of a mutation in the gene encoding the transporter, since this protein is only used to transport lysine, arginine and ornithine, The cystine reabsorption is normal.

Clinical manifestations: Type I is generally asymptomatic, and a few homozygotes may have mental retardation; type II dibasic amino acid urine is heavier than type I, and plasma dibasic amino acid concentration is lowered. In recent years, hepatocytes may be found to have dysfunction in this type of patient due to Lack of substrate lysine, arginine leads to ornithine circulatory disorder, can not completely detoxification, so patients with protein intolerance, manifested as hyperammonemia, vomiting, diarrhea, growth and mental retardation and splenomegaly Even hepatic encephalopathy, diagnosed by family history and urinary amino acid analysis.

3. Homocysteinuria This disease is a rare autosomal recessive disorder. Only the renal tubules are responsible for the transport of cystine. There is no corresponding transport disorder in the jejunum. Mild increase, dibasic amino acid displacement is normal, generally no urinary calculi.

4. The clinical manifestations of Hartnup's disease are paroxysmal. Symptoms often appear in childhood, puberty, and self-remission in the future. The main manifestations of this disease are:

(1) Pella-like skin rash: the exposed parts of the skin are red, dry and scaly, or chapped, foaming and exudation, sensitive to light, increased after sun exposure, and good response to nicotinamide treatment.

(2) paroxysmal cerebellar ataxia: mostly occurs in the severe period of the disease, manifested as gait instability, limb tremor, may have involuntary dance-like movements, poor eye aggregation, nystagmus, often diplopia, severe There may be seizures or fainting, occasional psychiatric symptoms and emotional instability, hallucinations, delirium or dementia, etc., the episode usually does not exceed 1 week, self-relieving, leaving no sequelae, mental normal or mild damage, short stature.

(3) Specific amino acid urine: mainly threonine, serine, histidine, alanine, hydroxyproline, normal discharge, so it can be distinguished from all amino acid urine, glycine, proline and hydroxyproline Normal discharge, can be distinguished from iminoglycine urine, the secondary amino acid excretion in urine is also normal, can be distinguished from cystine urine.

(4) Intestinal transport disorder: due to the decomposition of amino acids in the intestine, especially tryptophan, a large amount of purine metabolites are produced by the decomposition of bacteria. Indole sulfate (urine blue mother), mercapto-3-acetic acid can appear in the urine.

(5) Fecal examination: In addition to tryptophan in feces, there are a large number of branched-chain amino acids, phenylalanine, and other amino acids. The disease has little effect on the growth and development of children, and the height is only slightly affected. Basically normal.

5. Aminoglycineuria This disease is an autosomal recessive disorder, including proline, hydroxyproline and glycine, which is due to the co-transport system of the above three amino acids by renal tubular epithelial cells or to glycine or Sub-amino acid selective transport system is caused by disorders, patients are generally asymptomatic, occasionally mental retardation, convulsions and increased protein in cerebrospinal fluid, the disease can be divided into 4 types: type I with jejunal transport disorders, type II, III, IV There is no jejunal transport disorder, the prognosis of this disease is good, neonatal glycine urine, often reflects the total amino aciduria during the normal developmental period of 6 months after birth, persistent glycine urine appears in the children's Fanconi syndrome, pure glycine urine is more benign , generally asymptomatic.

6. Dicarboxy amino acid urinary system is an autosomal recessive disease caused by renal and small intestinal glutamate and aspartate transport disorders, clinically divided into two types: type I with jejunal absorption disorder, performance For fasting hypoglycemia and ketoacidosis (may be related to amino acid deficiency associated with gluconeogenesis), growth and mental development disorders in children, congenital hypothyroidism, episode hypoglycemia, decreased CO2 binding, blood stasis Increased in amino acid, a large amount of glutamate and aspartic acid in the urine, type II see jejunal absorption disorder, clinically very rare, generally asymptomatic, only urine urinary amino acid urine excretion increased.

7. Methionine malabsorption syndrome This disease is rare. It is caused by renal and intestinal epithelial cells to transport sulphur-containing amino acids. The clinical manifestations are mainly white hair, edema, mental retardation, paroxysmal hyperventilation, convulsions, urine. There is a special celery-like odor (caused by methionine urine and its degradation product -hydroxybutyrate), and there are also a large amount of phenylpyruvate and tyrosine in the urine.

8. -amino acid urinary excretion of more -amino acid urine, taurine, -alanine, -isobutyric acid appear in all amino acid urine, normal people excessive consumption of meat and seafood food urine Taurine can also occur in the disease. The clinical manifestations of this disease are epileptic seizures and coma, and -alanine--ketoglutarate transaminase activity is reduced.

Renal amino acid urine test

Renal amino acid urine is a group of diseases containing different amino acids in urine, so laboratory tests are also different.

Cystatinuria

(1) urinary sediment microscopic examination or acidification, concentrated and frozen urine precipitation can be seen in the hexagonal flat crystal.

(2) urine nitrohydrocyanate test was positive.

(3) Determination of urinary cystine per day by urine chromatography is greater than 300 mg / L, in addition to pyrrolidine and acridine can be measured in urine.

(4) The urine contains a lot of cystine, lysine, ornithine

2. Dibasic Amino Acids Urine The urine is detected in a large amount of dibasic amino acids, while the cystine is normal, and the corresponding amino acids in the blood are reduced.

3. Hypercystinuria This disease has only renal tubules to transport cystine, and there is no corresponding transport disorder in the jejunum. Only the cystine excretion in the urine is slightly increased, and the dibasic amino acid emissions are normal.

4. Hartnup disease laboratory examination found that the main amino acid urine, the urine is threonine, serine, histidine, alanine, and the hydroxyproline emission is normal, so it can be distinguished from the whole amino acid urine, glycine , proline and hydroxyproline excretion are normal, can be distinguished from iminoglycine urine, urinary two base amino acid excretion is also normal, can be distinguished from cystine urine, due to intestinal transport disorders, intestinal amino acids, especially Tryptophan is decomposed by bacteria to produce a large amount of sputum metabolites, sulphuric acid phenol (urine blue mother), thiol-3-acetic acid can be detected in the urine, fecal test found tryptophan, a large amount of alkaline, Phenylalanine, and other amino acids.

5. Iminoglycine urine The urine includes proline, hydroxyproline and glycine.

6. Dihydroxy amino acid urinary tract due to glutamate, aspartate transport disorder in the small intestine, can be expressed as fasting hypoglycemia and ketoacidosis (may be related to amino acid deficiency associated with gluconeogenesis), and specific Sexual amino acid urine, urine test showed glutamate, aspartic acid increased.

7. Methionine malabsorption syndrome There is a large amount of phenylpyruvate and tyrosine in the urine, and there is a celery-like special odor in the urine (caused by methionine urine and its degradation product -hydroxybutyrate).

8. -amino acid urinary -amino acid urine, taurine, -alanine, -isobutyric acid appear in all amino acid urine, normal people can also appear in urine when eating meat and seafood food too much Taurine.

Conventional X-ray abdominal plain film, angiography, B-ultrasound examination, often found bilateral urinary tract multiple, thin shadow, varying sizes of stones.

Diagnostic identification of renal amino acid urine

Diagnostic criteria

According to clinical manifestations, family history and urinary amino acid screening (qualitative) can make a preliminary diagnosis of various amino acid urine. Quantitative analysis of urine chromatography is also helpful for diagnosis and classification.

1. The basis for the diagnosis of cystineuria is as follows:

(1) History of family hereditary diseases.

(2) There are symptoms and signs of kidney stones such as colic, hematuria, urinary tract obstruction and/or urinary tract infection.

(3) Cyst stone stones repeatedly occur in the urinary tract, and hexagonal flat crystals can be seen by microscopic examination of urine sediment.

(4) KUB plain film sees multiple bilateral urinary tract, with thin shadows and different sizes of stones.

(5) urine nitrohydrocyanate test positive, can determine the diagnosis (take a small amount of stone powder in a test tube, add 1 drop of concentrated ammonia, add 1 drop of 5% sodium cyanide, after 5 minutes, add 3 drops 5% sodium nitroprusside, such as cherry red immediately, indicating positive, indicating the presence of cystine), urine has cystine and two base amino acids (normal highest value is cystine 74.88mmol / g creatinine, lysine , arginine, ornithine are each 8892, 918.4, 1665.4 mol / g creatinine).

2. Hartnup disease can diagnose the disease according to the following characteristics:

(1) There are typical clinical symptoms, lack of smokeless acid.

(2) There is psoriasis-like skin damage.

(3) Increased specific amino acid content in urine.

(4) In addition to tryptophan in the feces, there are a large number of branched proline, phenylalanine and other amino acids.

Differential diagnosis

The differential diagnosis of this disease is mainly between the identification of various types of renal amino acid urine, mainly based on the specific amino acids in the urine, and should be distinguished from the amino acid urine caused by other causes, such as: cystineuria mainly and cyst Isolate or cystine storage disease, homocysteine urine is differentiated, cystine disease is a systemic metabolic disease, and cystine is deposited in various tissues.

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