Aminoaciduria and cystinuria

Aminoaciduria (aminoaciduria) is an increase in the excretion of amino acids in the urine or the presence in the urine of amino acid products that are not normally contained in it (for example, ketone bodies).

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Causes aminoaciduria and cystinuria.

The reabsorption of most amino acids is carried out by the epithelial cells of the proximal tubules, which have 5 main transporters on the apical membrane. In addition, for some amino acids there are specific transporters.

Renal aminoacidurias develop with genetically determined or, less commonly, acquired dysfunction of the corresponding tubular transporter.

Non-renal aminoacidurias are caused by a persistent increase in the content of the corresponding amino acid in the blood, which is most often observed with a hereditary deficiency of the enzymes that ensure its metabolism, and/or its excessive formation.

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Symptoms aminoaciduria and cystinuria.

Aminoaciduria with excretion of cystine or dibasic amino acids

Cystinuria is combined with an increase in the excretion of dibasic amino acids or exists in isolation. There are three types of cystinuria.

Variants of cystinuria

Type	Peculiarities	Manifestations
I II III	Associated with lack of intestinal absorption of cystine and dibasic amino acids Associated with lack of intestinal absorption of cystine, but not dibasic amino acids Intestinal absorption of cystine and dibasic amino acids is reduced	Cystinuria only in homozygotes; aminoaciduria is not present in heterozygotes Aminoaciduria in homo- and heterozygotes; in the latter, its severity is less pronounced Aminoaciduria in both homo- and heterozygotes

"Classical" cystinuria is a disease inherited in an autosomal recessive manner and, as a rule, is combined with a violation of the absorption of this amino acid in the intestine. The clinical significance of insufficient absorption of cystine in the intestine is small.

Isolated hypercystinuria, not combined with an increase in the excretion of dibasic amino acids, is observed extremely rarely. As a rule, these patients do not have a burdened family history.

The clinical symptoms of cystinuria depend on the intensity of nephrolithiasis. Patients with cystinuria experience renal colic, hematuria, and a tendency to urinary tract infections. Ureteral obstruction occurs infrequently, mainly in men. With bilateral cystine nephrolithiasis, renal failure sometimes develops.

Two types of isolated dibasic aminoaciduria without cystinuria have been described. Type 1 is characterized by increased excretion of arginine, lysine, and ornithine. The disease is inherited in an autosomal recessive manner, with renal tubular dysfunction combined with impaired intestinal absorption of dibasic amino acids. Consumption of large amounts of protein by patients with this disease leads to increased ammonium ion levels in the blood and severe alkalosis, accompanied by vomiting, weakness, and impaired consciousness.

In isolated dibasic aminoaciduria type 2, the excretion of arginine, lysine, and ornithine is also increased, but episodes of hyperammonemia are not observed.

Isolated lysinuria is diagnosed extremely rarely. This variant of tubular dysfunction is always associated with mental retardation.

Aminoaciduria with excretion of neutral amino acids is represented by Hartnup disease and histidinuria. Clinical symptoms of aminoaciduria depend on the form of the disease.

Hartnup disease is named after the English family in which the disease was first described. Hartnup disease is caused by a deficiency of the tubular transporter of neutral amino acids. Less than half of the filtered alanine, asparagine, glutamine, isoleucine, leucine, methionine, phenylalanine, serine, threonine, tryptophan, tyrosine, and valine is reabsorbed. Histidine reabsorption is completely impaired. Intestinal absorption of neutral amino acids is also impaired in Hartnup disease.

The symptoms of Hartnup disease are mainly presented by signs associated with a deficiency of nicotinamide, formed mainly from tryptophan. Photodermatitis (like pellagra), cerebellar ataxia, emotional lability, and sometimes mental retardation are characteristic.

Isolated observations of isolated histidinuria are described. All patients were diagnosed with impaired intestinal absorption of this amino acid and mental retardation.

Iminoglycinuria and glycinuria

Iminoglycinuria is an autosomal recessive tubular dysfunction characterized by increased excretion of proline, hydroxyproline, and glycine. It is usually asymptomatic.

Isolated glycinuria is also a benign condition, apparently inherited in an autosomal dominant manner. Nephrolithiasis is occasionally observed.

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Aminoaciduria with excretion of dicarboxylic amino acids

Increased excretion of dicarboxylic amino acids (aspartic and glutamic) is observed extremely rarely, and is asymptomatic. Combinations of this tubular dysfunction with hypothyroidism and mental retardation have been described, but their connection has not been established.

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Forms

Aminoaciduria is divided into renal and non-renal.

Renal aminoacidurias

Disruption of amino acid transport	Diseases
Cystine and dibasic amino acids	"Classic" cystinuria Isolated hypercystinuria Dibasic aminoaciduria - type 1 - type 2 Lysinuria
Neutral amino acids	Hartnup disease Histidinuria
Glycine and imino acids	Iminoglycinuria Glycinuria
Dicarboxylic amino acids	Dicarboxylic aminoacidurias

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Diagnostics aminoaciduria and cystinuria.

Laboratory diagnostics of cystinuria

The diagnosis of cystinuria is confirmed by detecting cystine crystals in the urine. A qualitative colorimetric cyanide-nitroprusside test is used for screening.

The diagnosis of Hartnup disease is confirmed by testing the neutral amino acid content of urine using chromatography.

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Treatment aminoaciduria and cystinuria.

Treatment of cystinuria involves reducing the concentration of cystine in the urine and increasing its solubility. Constant alkalinization of urine (target pH > 7.5) and intake of large amounts of fluid (4-10 l/day) are recommended.

The use of penicillamine in cystinuria is advisable due to its ability to form a highly soluble disulfide complex with cystine. Penicillamine is prescribed at a dosage of 30 mg/kg/day; in adults, if necessary, the dosage is increased to 2 g/day. In patients taking penicillamine, it is necessary to monitor the levels of protein excretion in the urine due to the risk of developing membranous nephropathy with nephrotic syndrome.

Patients with cystinuria are advised to limit their consumption of table salt. In the case of cystine nephrolithiasis, generally accepted surgical treatment methods are used.

Patients with isolated dibasic aminoaciduria without cystinuria are advised to follow a low-protein diet.

Nicotinamide is prescribed to treat Hartnup disease.