What is Cystinosis?

Cystineuria is a familial hereditary disease. It is an autosomal recessive disease. It consists of the proximal renal tubular epithelial cells and the jejunal mucosa of dibasic amino acids (including lysine, arginine, ornithine). Acid) and cystine. The disease is rare clinically and occurs mainly in children and infants. Cysteine is localized in the lysosome of the cell, and its crystals are deposited in the cornea, conjunctiva, bone marrow, lymph nodes, white blood cells, kidneys and other internal organs, causing damage to renal tubules and glomerular function, and eventually develop into uremia, more than prepuberty death.

Cystineuria is a familial hereditary disease. It is an autosomal recessive disease. It consists of the proximal renal tubular epithelial cells and the jejunal mucosa of dibasic amino acids (including lysine, arginine, ornithine). Acid) and cystine. The disease is rare clinically and occurs mainly in children and infants. Cysteine is localized in the lysosome of the cell, and its crystals are deposited in the cornea, conjunctiva, bone marrow, lymph nodes, white blood cells, kidneys and other internal organs, causing damage to renal tubules and glomerular function, and eventually develop into uremia, more than prepuberty death.

Causes of cystine in children

Cystine disease has the same incidence in males and females. Parents cannot inherit the disease vertically to their children, but siblings often have multiple diseases. Cystine disease is an autosomal recessive genetic disease, and the patients are homozygous. The parents are heterozygotes who carry the disease. The clinical manifestations of the disease include severe infant nephropathy, young patients with intermediate types, and adult benign types. This indicates that the disease is genetically heterogeneous and that there is genetic heterogeneity.

Clinical manifestations of cystine in children

Renal lesion type

It is mainly found in children and infants.

(1) The early initial manifestations are related to the progressive damage of renal tubules, with symptoms such as thirst, polyuria, dehydration, etc. At the age of 1 years, they show growth retardation, rickets, acidosis and various renal tubular dysfunctions, glucosuria, amino acid urine , Phosphate urine and increased potassium in urine, children with fair complexion, pale yellow hair, most of them developed severe photophobia within a few years of age, ophthalmologic slit lamp examination showed cornea and conjunctiva with uniformly dispersed wire-like reflective objects; Hypopigmentation spots and irregularly distributed, irregularly sized pigment filaments can be seen at the edge of the retina, which is called "characteristic marginal retinopathy", which is helpful for the diagnosis of cystine disease.

(2) In the later stage, due to the progressive damage of the glomerulus, the glomerular filtration rate was reduced, and corresponding clinical manifestations such as azotemia, electrolyte disturbance, metabolic acidosis, and growth arrest occurred. As the disease progressed, serious clinical manifestations appeared. Anemia, edema and other symptoms.

2. Benign type

No retinopathy and renal insufficiency; cystine crystals were deposited in the cornea, bone marrow, and white blood cells, but they did not cause symptoms, and this type of patients can be adults.

3.Intermediate type

Also known as late-onset or juvenile type, the patient develops renal insufficiency, whose symptoms do not manifest until adolescence, with incomplete Fanconi syndrome and slow-moving glomerular insufficiency.

Pediatric cystine disease test

Urine contains a large amount of cystine, lysine, arginine, and ornithine. Cysteine excretes an average of 730 mg per day (normally the highest value is about 18 mg / g urine creatinine).

1. Urinary cystine crystal inspection

The morning urine was taken as a centrifugal precipitate, and hexagonal flat crystals similar to the benzene ring were found under light microscopy. The appearance of the crystals often showed that the urinary cystine concentration exceeded 200-250 mg / L.

2. Cyanide nitroprusside test

Grind the stones into powder, put a little into the test tube, add 1 drop of concentrated ammonia water, and then add 1 drop of 5% sodium cyanide, 5 minutes later add 3 drops of 5% sodium nitroprusside, as shown immediately after the characteristic dark cherry red Positive, indicating the presence of cystine, but homocysteine, pyruvate, all amino acid urine and certain drugs can be false positive, attention should be paid to identification, in addition, because urinary cystine can be volatile, pay attention to false negative.

3. Quantitative determination of urine chromatography

It is helpful for diagnosis and typing.

Routine B-ultrasound, plain radiographs, angiography and CT should be done to help diagnose and differentiate.

Pediatric cystine disease diagnosis

According to the clinical manifestations of children, there are vitamin D deficiency rickets, Fanconi syndrome, etc .; cystine crystals exist in the conjunctiva, cornea and peripheral leukocytes, bone marrow reticuloendothelial cells, evidence of cystine deposition in the kidney, and kidney The characteristics of pathological changes can confirm the diagnosis.

Pediatric Cystine Treatment

This disease is a hereditary disease and there is no cure for it. It mainly prevents the formation of cystine stones and its complications.

Diet control

A diet low in methionine (the most important precursor of cystine) can sometimes moderately decrease cystine urine.

2. Increase drinking water

Especially at night, in order to prevent the precipitation of cystine crystals when the urine is concentrated, the daily water intake is at least 4L or more, so that the urinary cystine concentration is diluted and kept below 250mg / L.

3. Alkali urine

Can be taken with sodium citrate or sodium bicarbonate (10 38g / d) to alkalinize urine (make urine pH> 7.5), increase cystine solubility and prevent stone formation. Generally, when urine pH 7.5, cystamine The solubility of the acid is the highest (about 250mg / L), but there is a risk of promoting the deposition of calcium phosphate. You can also take acetazolamide (acetazolamide) (250-500mg) before bedtime.

4. Drug treatment

(1) Penicillamine is -dimethylcysteine, which can reduce free cystine in urine by about 50%, and at the same time interact with cystine to generate soluble cysteine-penicillamine disulfide compounds It is excreted from the urine, so it can prevent the formation of stones. Usage: 1-2g / d, 3 to 4 times. This medicine often has side effects such as rash, fever, joint pain, bone marrow suppression, lupus-like reaction, kidney damage (nephropathy Syndrome), etc. Therefore, this medicine is only used in the cases where the above general treatment cannot be controlled and severe cystine stones.

(2) Newer drugs, such as N-acetyl-D-penicillamine, have lower toxicity and have the same effect.

(3) Thiopronin works like penicillamine, but has less toxicity.

(4) Dithiothreitol (DTT) can reduce intracellular cystine content.

(5) Thiolamine (cystine amine) can remove free cystine in cells.

(6) The efficacy of high-dose vitamins is uncertain.

5. Kidney Stone Treatment

Consider extracorporeal shock wave lithotripsy or surgical stone removal.

6. Symptomatic treatment

Maintain water and electricity balance, correct acidosis, give large doses of vitamin D to treat rickets, prevent urinary tract infections and urinary tract obstruction.

7. Dialysis Therapy and Kidney Transplant

Uremia was treated with dialysis or kidney transplantation.

(1) Dialysis therapy Although cystine deposited in tissues and cells cannot be removed, it can continue to grow in patients with renal failure and prepare for kidney transplantation.

(2) Renal transplantation Symptoms improved and growth recovered after surgery. It has been reported that cystine deposition can still be found in the transplanted kidney;