(A) causes cystinosis in the male,
Girls morbidity same. Parents
can not be vertically inherited the disease to their children, but often
multiple sibling incidence. Cystine disease is an autosomal
recessive genetic disease, the patient was homozygous, their parents to carry
the disease heterozygotes. The clinical
disease with severe renal variant infants, young and adult patients with benign
intermediate type 3, indicating that the genetic heterogeneity of the disease,
while there is genetic heterogeneity.
(Two)
the pathogenesis of intracellular lysosomal cystine deposition in confined and
difficult with the extracellular exchange, but the biochemical mechanism is
unknown; currently considered within the cell cystine calm reason, most likely
cystine or cysteine in the
spaces between cells or abnormal intracellular translocation, resulting in
deposition of cystine sick children in the liver, spleen, bone marrow,
peripheral blood leukocytes, lymph nodes, kidney and cornea deposition.
1
cystinosis is characterized systemic tissues cystine crystal deposition, the
deposition of parts of the reticuloendothelial cells of bone marrow, liver,
spleen, lymph nodes, peripheral blood leukocytes, kidney medulla, cortex and
mesangial , conjunctival and uveitis. (2) deposition of cystine kidney cause renal
tissue damage caused by renal failure. Appearance pale
kidney cortex and medulla unclear boundaries; microscopic structural damage
nephron glomerular showed hyaline degeneration, renal tubular epithelial cells
are normal dice-shaped cells are replaced. Becomes narrow and shorten the proximal tubule, was
"swan neck" deformity.
Children with
cystinosis symptoms
1 nephropathy
type is mainly seen in children and infants.
(1) Early: initially presented with
progressive renal injury related symptoms of polydipsia, polyuria, dehydration.
A
performance at the age of growth arrest, rickets, renal tubular acidosis and a
variety of functional abnormalities of glycosuria, amino acids in urine,
increased urinary potassium phosphate in urine and so on. Children with fair complexion, hair, pale yellow.
Most
serious occurred in teens photophobia, eye cornea and conjunctiva slit lamp
examination showed scattered in a uniform wire-like reflective objects;
addition, the retina can see the edge of hypopigmentation spots with irregular
distribution, ranging from the size of the pigment silk, called "edge characteristic retinopathy," help
cystine diagnosis.
(2) Late: Due
to progressive glomerular injury, caused by reduced glomerular filtration rate,
azotemia, electrolyte imbalance, metabolic acidosis, growth retardation, and
other relevant clinical manifestations. With the progress of the disease, severe anemia,
edema and other symptoms.
(2) benign type
without retinopathy and renal insufficiency; corneal, bone marrow and white
blood cells in cystine crystal deposition, but does not produce symptoms, this
type of patients can adulthood.
3
intermediate, also known as delayed or young adults. Patients with renal
insufficiency, the symptoms manifest themselves until adolescence, there is
incomplete Fanconi syndrome and the slow progress of glomerular
dysfunction.
According
to clinical manifestations in children, the presence of vitamin D deficiency
rickets, Fanconi syndrome, etc.; in the conjunctiva, cornea and surrounding
white blood cells, bone marrow reticuloendothelial cells in the presence of
cystine crystals. Deposition
of cystine in the kidney as well as evidence of pathological changes
characteristic of the disease can be diagnosed.
Children with cystinosis diagnosis
Children with cystinosis inspection laboratoryUrine contains a large number of cystine, lysine,
arginine and ornithine. The average daily urinary excretion of
cystine up to 730mg (normal maximum value of about 18mg / g urine creatinine).
A urinary cystine
crystals take morning urine checked for centrifugation, visible under the light
microscope with benzene-type hexagonal tabular crystals similar. Crystallization occurs often show urinary
cystine concentration exceeds 200 ~ 250mg / L. 2 cyanide
nitroprusside test the stone into powder, put a little in a test tube, add 1
drop of concentrated ammonia, after the addition of a drop of 5% sodium cyanide,
5min after the addition of 3 drops of 5% sodium nitroprusside, such as
Now the characteristic deep cherry
red shown as positive, indicates the presence of cystine. However, the same type of cystine,
pyruvate, all amino acids in urine and certain drugs was a false positive,
attention should be identified. In
addition, because of the urine row cystine can be presented volatility, should
pay attention to false negative. 3
chromatographic quantitative determination of urine on the diagnosis and
classification of help. Routine should be done renal B, X-ray,
angiography and CT, to help diagnosis and differential
diagnosis.
Differential diagnosis of
children cystinosisCompared
with other amino acids in urine disease identification, based on clinical and
laboratory examination and more can be confirmed.
Children with cystinosis complications
Can occur dehydration,
hypokalemia, metabolic acidosis, anemia, nutritional disorders, rickets,
end-stage renal failure. Small number of patients
hyperuricemia, hereditary hypocalcemia, hemophilia, muscular atrophy, hereditary
pancreatitis, such as retinitis pigmentosa.
Children with cystinosis prevention and treatment
of
(A) the treatment of this
disease is hereditary diseases, no cure for. The main control cystine stone formation and its
complications.
1
diet low methionine (cystine most important predecessor) diet, sometimes
moderate decrease urinary cystine.
(2)
increase the amount of water, especially at night, in order to prevent the
precipitation of cystine crystals concentrate urine, the daily intake of water
above at least 4L, dilute the concentration of the urinary cystine maintained at
250mg / L or less.
3
alkalization of urine can be served sodium citrate or sodium bicarbonate (10 ~
38g / d) to alkaline urine (so that the urine pH> 7.5), can increase the
solubility of cystine to prevent stone formation. General urinary pH 7.5,
the solubility of cystine highest (about dissolving 250mg / L), but there is
danger of promoting calcium phosphate deposition. Can also be taken at bedtime acetazolamide
(vinegar azole sulfonamides) (250 ~ 500mg).
4
drug treatment
(1)
penicillamine (D-penicillamine): is a β-dimethyl cysteine, which can reduce
urinary cystine about 50% of the free, while soluble cysteine reacts with
cystine - Penicillium amine disulfide
compounds from the urine, it can prevent stone formation. Usage: 1 ~ 2g / d, min to 4 times service. Often side effects of this drug,
such as rash, fever, joint pain, bone marrow suppression, lupus reactions and
kidney damage (nephrotic syndrome) and so on. Thus, the drug is only used for the general
treatment of cystine stones can not be controlled and serious
cases.
(2) the newer
drugs: such as N-acetyl-D-penicillamine (N-acetyl-D-penicillamine), low
toxicity, have the same effect.
(3) Tiopronin
(Mercaptopropionylglycine): the role with penicillamine, but less
toxic.
(4)
dithiothreitol (DTT): to reduce the intracellular cystine.
(5) a mercapto ethylamine (cystine amine): to
remove free intracellular cystine.
(6) large doses of vitamins: effects are not
sure.
5 can be considered the
treatment of kidney stones extracorporeal shock wave lithotripsy or stone
surgery.
6 symptomatic treatment
to maintain water balance, correct acidosis. Given large doses of vitamin D therapy rickets.
Prevention and treatment of urinary tract
infections, urinary tract obstruction.
7 dialysis and kidney transplantation then be
uremia dialysis or kidney transplantation.
(1) dialysis therapy:
although not remove cell and tissue deposition of cystine, it can continue to
grow in patients with renal failure and renal transplant
preparation.
(2) renal
transplantation: postoperative symptoms improve, growth resumed. There are reports of renal transplantation
can still found cystine deposition; kidney transplant long-term effects to be
determined.
(Two) the
prognosis of the disease with poor prognosis, more than before puberty develop
into uremia and death.
Children with
cystinosis care
Homocystinuria is a
familial genetic disease, an autosomal recessive genetic disease, prevention
measures may be hereditary disease preventive measures. To
reduce the incidence of this disease, prevention should penetrate to prenatal
pregnancy: premarital medical examination in the prevention of birth defects
play an active role, the role depends on the inspection items and content,
including serological tests (such as hepatitis B virus, Treponema pallidum,
AIDS
virus), reproductive system checks (such as screening for cervical
inflammation), general physical examination (such as blood pressure, ECG), and
asking a family history of the disease, such as personal medical history,
genetic diseases do consulting work. Pregnant women try to
avoid risk factors, including away from the smoke, alcohol, drugs, radiation,
pesticides, noise, volatile harmful gases, toxic heavy metals. In the course of
prenatal care during pregnancy need to be systematic screening for birth
defects, including regular ultrasound, serological screening, etc., if
necessary, carry chromosome. Once the abnormal
results need to be clear whether you want to terminate the pregnancy; safety of
the fetus in utero; existence after birth complications, whether to treat, the
prognosis is how and so on. To take practical
measures for diagnosis and treatment.
