Cystinuria: what is it, causes, symptoms, treatment, prognosis

What is cystinuria?

Cystinuria- hereditary metabolic disorder characterized by abnormal movements (transport) in the intestines and kidneys of certain organic chemical compounds (amino acids). These include cystine, lysine, arginine, and ornithine. Excessive amounts of undissolved cystine in the urine (cystinuria) causes the formation of kidney stones, bladder and / or ureter.

There are four subtypes of cystinuria - type I, II, III and hypercystinuria. In type I cystinuria, there is a violation of the active transport of cystine and amino acids (dibasic) lysine, arginine and ornithine in the kidneys and small intestine. People who carry the gene for this type of disorder usually have no symptoms. (A "carrier" is someone who has only one gene mutation for cystinuria, not two.)

In type II cystinuria, the transport of cystine and lysine is severely impaired in the kidneys and only slightly impaired in the intestine. In type III cystinuria, the renal transport of cystine and lysine is impaired; intestinal transport is normal. People who carry the gene for this form of the disease usually have slightly elevated levels of cystine and lysine in their urine. With hypercystinuria, there is usually a moderate increase in urinary cystine levels; intestinal absorption of cystine and dibasic amino acids is normal.

Signs and symptoms

People with cystinuria secrete abnormally high levels of cystine in their urine. The cystine level is so high that it remains undissolved in the urine. The amino acids lysine, arginine, and ornithine are also excreted in large quantities by people with this disorder. However, these amino acids dissolve more easily in urine (more soluble) and are not associated with any specific symptoms.

Despite the fact that symptoms of cystinuria can occur in children in the first year of life, they usually appear for the first time between the ages of 10-30. The initial symptom of cystinuria is usually severe pain in the lower back or on the sides of the abdomen (renal colic). Other symptoms may include blood in urine (hematuria), obstruction of the urinary tract (ureters) and / or urinary tract infections. Frequent relapses can ultimately damage the kidneys and renal failure.

People with cystinuria usually develop stones that are usually small in size with a jagged crystal surface. These stones may be accompanied by the presence of urinary calculi, which is composed of yellowish brown hexagonal crystals. All patients with urinary stones should be screened for cystinuria.

Causes

Cystinuria symptoms develop due to abnormal cystine transport.

Cystinuria is inherited as an autosomal recessive genetic trait. Human traits, including classic genetic diseases, are the product of the interaction of two genes, one from the father and the other from the mother. Recessive genetic disorders occur when a person inherits two copies of an altered gene for the same trait, one from each parent.

If a person inherits one normal gene and one gene for the disease, the person will carry the disease but usually will not show symptoms. The risk for two carrier parents who both pass on the altered gene and have a sick child is 25% with each pregnancy. The risk of having a carrier child, like the parents, is 50% with each pregnancy. The probability for a child to receive normal genes from both parents is 25%. The risk is the same for men and women.

Affected populations

Cystinuria is a hereditary metabolic disorder that affects men and women in equal amounts. Symptoms of this disorder usually begin between the ages of 10 and 30, although increased cystine excretion can be detected in infancy. The disorder occurs in about 1 in 20,000 people.

Diagnostics

If a person periodically develops kidney stones, tests are done for the presence of cystinuria. The collected stones are analyzed.

Cystine crystals can be seen on microscopic examination of urine (urine analysis), and a high cystine content is found in the urine.

Related disorders

Symptoms of the following disorders may be similar to those of cystinuria. Comparisons can be useful for differential diagnosis.

• Aminoaciduria dibasic - hereditary defect (r) in the transport of lysine, ornithine and arginine (but not cystine). In dibasic aminoaciduria, the transport of lysine, arginine and ornithine is disrupted, which leads to an increase in the level of these amino acids in the urine.
• Cystinosis - a rare hereditary disorder of cystine transport, characterized by the accumulation of cystine in the cells of the body, especially in the kidneys and eyes. Symptoms of this disorder include the presence of cystine crystals in the urine, the discharge of abnormally large urine volumes (polyuria), abnormally low circulating potassium levels (hypokalemia), and / or renal failure. The accumulation of cystine in the eyes can lead to increased sensitivity to light (photophobia), headache and / or itching and burning eyes. Symptoms usually begin in infancy.

Standard treatments

The main goal of cystinuria treatment is to reduce the concentration of cystine in the urine. Drinking a lot of fluids both during the day and at night maintains a large urine volume and decreases the concentration of cystine in the urine. Increasing the alkalinity of the urine (alkalinization) helps the cystine dissolve in the urine more quickly and may also prevent the formation of stones. Medications that may be prescribed to make the urine more alkaline include potassium citrate and acetazolamide. This drug therapy is accompanied by dietary salt restriction.

Another approach to treating cystinuria is to administer D-penicillamine, although this drug has some risks of side effects. D-penicillamine promotes the formation of cystine in another chemical form (mixed disulfide), which is more soluble in urine and excreted from the body.

Alpha-mercaptopropionylglycine, also known as Thiopronine, has been approved for the treatment of cystinuria. Thiopronine has been shown to reduce the level of cystine in the urine of patients with cystinuria. Another medicine that is sometimes used is Captopril.

Sometimes kidney and / or bladder surgery is required, but stones usually recur. Small stones can go away on their own, with a lot of fluid and, if necessary, pain relievers. If spontaneous passage of the stone does not occur, the stones can be removed with a surgical procedure.

Other treatments are symptomatic and supportive.

Forecast

Cystinuria is a chronic condition and many sick people experience recurrence of cystine stones in the urinary tract (kidneys, bladder, and ureters). In rare cases, frequent kidney stones can lead to tissue damage or even kidney failure.