Pediatric cystinosis
Introduction
Introduction to pediatric cystine disease Cysturiuria (cystinuria) is a familial hereditary disease that is an autosomal recessive disorder that is caused by proximal tubular epithelial cells and jejunal mucosa to two base amino acids (including lysine, arginine). , ornithine) and cystine and other transport disorders. The disease is clinically rare, mainly in children and infants. Cystine is restricted in the lysosomes of cells, and its crystals are deposited in the cornea, conjunctiva, bone marrow, lymph nodes, white blood cells, kidneys and other internal organs, causing renal tubular and glomerular dysfunction, and finally develop into uremia, more than before puberty. death. basic knowledge The proportion of illness: 0.001% Susceptible people: children Mode of infection: non-infectious Complications: dehydration hyperuricemia hemophilia
Cause
Pediatric cystine disease etiology
Causes
Cystaceous disease has the same incidence rate in males and females. Parents cannot inherit the disease vertically to their children, but there are often multiple cases between siblings. Cystine disease is an autosomal recessive hereditary disease, and patients are homozygous. The parents are heterozygous for carrying this disease. The disease has clinically serious infantile nephropathy type, intermediate type of young patients and three benign types of adult, indicating the genetic heterogeneity of the disease and the genetic heterogeneity.
Pathogenesis
The intracellular cystine deposition is restricted to lysosomes and is not easily exchanged with extracellular cells, but the biochemical mechanism is unknown. It is currently believed that the cause of cystine in cells is most likely cystine or cysteine. Intercellular or intracellular transport abnormalities cause cystine deposition in the liver, spleen, bone marrow, peripheral blood leukocytes, lymph nodes, kidneys and cornea.
1. Characteristics of cystine disease: There are cystine crystal deposits in the whole body tissues, and the deposited sites are the reticuloendothelial cells of the bone marrow, liver, spleen, lymph nodes, peripheral blood leukocytes, renal medulla, cortex and glomerulus. Membrane, conjunctiva and ocular pigment layer.
2. Cystine deposition in the kidney: causing renal tissue damage leading to renal failure, the appearance of the kidney is pale, the boundary between the cortex and the medulla is unclear; the structure of the nephron is destroyed under the microscope, the glomerulus is glassy, and the renal tubule is Normal epithelial cells are replaced by sickle cells, and the proximal tubules are narrowed and shortened, showing a "swan neck" deformity.
Prevention
Pediatric cystine disease prevention
Cysturia is a familial hereditary disease that is an autosomal recessive disorder. Therefore, preventive measures can be based on hereditary disease prevention measures. To reduce the incidence of this disease, prevention should be carried out from pre-pregnancy to prenatal: premarital medical examination Play a positive role in the prevention of birth defects, the size of the effect depends on the inspection items and content, mainly including serological tests (such as hepatitis B virus, Treponema pallidum, HIV), reproductive system tests (such as screening for cervical inflammation), general medical examination (such as blood pressure, electrocardiogram) and ask about the family history of the disease, personal medical history, etc., do a good job in genetic disease counseling.
Complication
Pediatric cystine disease complications Complications dehydration hyperuricemia hemophilia
Can occur dehydration, hypokalemia, metabolic acidosis, anemia, nutritional disorders, rickets, advanced renal failure, etc., a small number of patients can be combined with hyperuricemia, hereditary hypocalcemia, hemophilia, muscle atrophy, Hereditary pancreatitis, retinitis pigmentosa, etc.
Symptom
Symptoms of cystineosis in children Common symptoms Polyuria diabetes Vitamin D deficiency Metabolic acidosis Photophobic azotemia Amino acid urinary edema Retinal Roth plaque
1. Renal lesions: mainly found in children and infants.
(1) Early: The initial performance is related to progressive tubular injury. Symptoms include polydipsia, polyuria, dehydration, etc., growth arrest at 1 year old, rickets, acidosis and various renal tubular dysfunction, glucoseuria, amino acids Urine, phosphate urine and increased urinary potassium, children with fair complexion, hair is pale yellow, most of them have severe photophobia in a few years, ophthalmic slit lamp examination can see the cornea and conjunctiva have scattered metal wire-like reflective objects; In addition, pigmentation spots with irregular hypodermia and irregular distribution, and different sizes of pigmented filaments, called "characteristic edge retinopathy", can help to diagnose cystine disease.
(2) Late stage: due to the progressive damage of glomeruli, the glomerular filtration rate is reduced, and the corresponding clinical manifestations such as azotemia, electrolyte imbalance, metabolic acidosis, growth stagnation, etc. appear as the disease progresses. Severe anemia, edema and other symptoms.
2. Benign type: no retinopathy and renal insufficiency; there are cystine crystal deposits in the cornea, bone marrow and white blood cells, but no symptoms, this type of patients can be adult.
3. Intermediate: Also known as late-onset or young-type, the patient develops renal insufficiency, and the symptoms are manifested in adolescence, with incomplete Fanconi syndrome and slow-moving glomerular insufficiency.
Examine
Pediatric cystine disease examination
The urine contains a large amount of cystine, lysine, arginine and ornithine, and the average daily urinary excretion of cystine can reach 730 mg (the normal maximum value is about 18 mg/g urinary creatinine).
1. Examination of urinary cystine crystal: Take morning urine for centrifugation, and the hexagonal flat shape and benzene ring-like crystals can be seen under light microscopy. The crystallization shows that the concentration of urinary cystine exceeds 200-250 mg/L.
2. Cyanide nitroprusside test: The stone is ground into a powder, put a little in the test tube, add 1 drop of concentrated ammonia water, then add 1 drop of 5% sodium cyanide, and add 3 drops of 5% sodium nitroprusside after 5 minutes. If the characteristic deep cherry red is immediately positive, it means that there is cystine, but the homocysteine, pyruvic acid, whole amino acid urine and some drugs can be false positive, should be identified, in addition, due to urinary cystatin Acids can be volatility and attention should be paid to false negatives.
3. Quantitative measurement by urine chromatography: it is helpful for diagnosis and classification.
Routine kidney ultrasound, X-ray film, angiography and CT examination should be done to aid diagnosis and differential diagnosis.
Diagnosis
Diagnosis and diagnosis of cystineosis in children
According to the clinical manifestations of children, there are vitamin D deficiency rickets, Fanconi syndrome, etc.; in the conjunctiva, cornea and surrounding white blood cells, bone marrow reticular endothelial cells have cystine crystals, evidence of cystine deposition in the kidneys and kidneys The characteristics of pathological changes can confirm the disease.
Different from other amino acid urinary diseases, it can be diagnosed according to clinical and laboratory tests.
