OVERVIEW
Cystinuria is a familial, autosomal recessive disorder caused by impaired transport of dibasic amino acids (including lysine, arginine, and ornithine) and cystine by proximal renal tubular epithelial cells and jejunal mucosa. The disease is clinically rare and occurs mainly in children and infants. Cystine is confined to the lysosomes of the cells, and its crystals are deposited in the cornea, conjunctiva, bone marrow, lymph nodes, leukocytes, kidneys and other internal organs, resulting in tubular and glomerular damage, and finally developing into uremia, which is most often caused by death before puberty.
Etiology
Cystinosis is equally prevalent in males and females, and both parents cannot vertically transmit the disease to their children, but there is often more than one case among siblings. Cystinosis is an autosomal recessive disorder, in which the patient is a pureblooded person whose parents are heterozygous for carrying the disease, and there are three types of the disease clinically, the severe nephropathic type in infants, the intermediate type in young patients, and the benign type in adults, which indicates the polyphasic nature of inheritance of the disease, and the simultaneous presence of This indicates the polyphasic nature of the inheritance of the disease, as well as the unevenness of inheritance.
Symptoms
1. Nephropathy
It is mainly seen in children and infants.
(1) Early stage The initial manifestations are associated with progressive tubular damage, with symptoms such as thirst, polyuria, and dehydration, etc. At the age of 1 year, the symptoms include growth retardation, rickets, acidosis, and multiple tubular abnormalities; glucosuria, aminoaciduria, phosphateuria, and increase in urinary potassium, etc. The children’s complexion is fair, the hairs are yellowish, and most of them develop severe photophobia within a few years.
(2) Late stage Due to the progressive glomerular injury, the glomerular filtration rate decreases, azotemia, electrolyte disorders, metabolic acidosis, growth retardation and other corresponding clinical manifestations, with the progression of the disease, severe anemia, edema and other symptoms.
2. Benign type
There is no retinopathy and renal insufficiency; there is deposition of cystine crystals in the cornea, bone marrow and leukocytes, but it does not produce symptoms, and all patients of this type can reach adulthood.
3. Intermediate type
Also known as the delayed or young-onset type, patients develop renal insufficiency that does not manifest until young adulthood, with incomplete Fanconi syndrome and slowly progressive glomerular insufficiency.
Examination
Urine contains large amounts of cystine, lysine, arginine and ornithine, and the average daily urinary excretion of cystine is up to 730mg (the normal maximum value is about 18mg/g urinary creatinine).
1. Urine cystine crystal examination
Morning urine for centrifugal precipitation, light microscopy can be seen under the hexagonal flat and benzene ring type similar to the crystals, crystals often indicate that the concentration of urinary cystine more than 200 ~ 250mg / L.
2. Cyanide nitrate test
Powder the stone, put a little in the test tube, add 1 drop of concentrated ammonia, then add 1 drop of 5% sodium cyanide, 5 minutes later, add three drops of 5% sodium nitroprusside, such as immediately out of the characteristic deep cherry red color is positive, indicating the presence of cystine.
3. Urine chromatography quantitative determination
It is helpful in confirming the diagnosis and typing.
4. Renal ultrasound, X-ray film, imaging and CT examination
Renal ultrasound, radiographs, contrast and CT should be routinely performed to aid in diagnosis.
Diagnosis
The diagnosis is confirmed on the basis of history, presence of vitamin D deficiency rickets, Fanconi’s syndrome, etc; presence of cystine crystals in conjunctiva, cornea and peripheral leukocytes, bone marrow reticuloendothelial cells, evidence of cystine deposition in the kidneys, and features of renal pathologic changes.
Treatment.
This is a hereditary disease with no radical cure, the main prevention and treatment of cystine stone formation and its complications.
1. Dietary control
A diet low in methionine (the most important precursor of cystine) can sometimes moderately reduce cystinuria.
2. Increase water intake
Especially at night, in order to prevent the precipitation of cystine crystals when the urine is concentrated, the amount of water intake per day should be at least 4L or more, so as to dilute the concentration of urinary cystine and keep it below 250mg/L.
3. Alkalize urine
Sodium citrate or sodium bicarbonate can be taken to alkalize the urine (to make the urine pH>7.5), which can increase the solubility of cystine and prevent the formation of stones. Generally speaking, when the urine pH is 7.5, the solubility of cystine is the highest (250mg/L), but there is a risk of promoting the deposition of calcium phosphate, and acetazolamide (vinazolylsulfamethoxazole) can also be taken before bedtime.
4.Drug treatment
(1) Penicillamine can reduce the free cystine in the urine 50%, and at the same time and cystine to generate soluble cysteine – penicillamine disulfide compounds discharged from the urine, so it can prevent the formation of stones, this drug is only used for general treatment can not be controlled and serious cystine stone cases.
(2) Newer drugs such as N-acetyl-D-penicillamine, with lower toxicity, have the same effect.
(3) Thiopronin The same effect as penicillamine, but less toxic.
(4) Dithiothreitol can reduce intracellular cystine content.
(5) Mercaptoethylamine (cystine amine) can remove free cystine in the cell.
5. Kidney stone treatment
Extracorporeal shock wave lithotripsy or surgical stone removal.
6. Symptomatic treatment
Maintain water and electricity balance, correct acidosis, give high dose vitamin D to treat rickets, prevent urinary tract infection and urinary tract obstruction.
7. Dialysis therapy and kidney transplantation
Dialysis or kidney transplantation should be given for uremia.
(1) Dialysis therapy Although it cannot remove the cystine deposited in tissues and cells, it can make the patients with renal failure continue to grow and prepare for kidney transplantation.
(2) Kidney transplantation Symptoms improve and growth resumes after surgery. Cystine deposits can still be found in transplanted kidneys; long-term results of kidney transplantation are to be determined.