congenital nephrotic syndrome
Introduction
Introduction to congenital nephrotic syndrome Congenital nephrotic syndrome (CNS) refers to nephrotic syndrome that occurs within 3 months after birth. It has the same clinical manifestations as childhood nephrotic syndrome, that is, a large amount of proteinuria at birth or within 3 months after birth. Edema, hyperlipidemia and hypoproteinemia are classified into two major categories: hereditary nephrotic syndrome and non-hereditary nephrotic syndrome. basic knowledge The proportion of illness: 0.006% Susceptible people: seen in infants and young children Mode of infection: non-infectious Complications: edema, ascites
Cause
Causes of congenital nephrotic syndrome
(1) Causes of the disease
Congenital nephrotic syndrome Finnish and non-Finnish are autosomal recessive diseases, and their genes are located on the long arm of chromosome 19, so the offspring of the close relatives have a high incidence of offspring, while Drash syndrome often has secondary factors. .
(two) pathogenesis
It has been clarified that the Finnish congenital nephrotic syndrome is an autosomal recessive hereditary disease. It is speculated that the genetic disease causes the heparan sulfate metabolism disorder, the glomerular basement membrane lacks heparan sulfate, and the negative charge barrier damage leads to a large amount of proteinuria. The main pathogenesis of this disease.
In 1966, Norio conducted a genetic survey of 57 Finnish families, and identified this as autosomal recessive inheritance. The defect gene was located on the long arm of chromosome 19 and 13.1. In 1983, Vernier et al. detected 5 cases of congenital nephropathy with cationic probe PEI. Significantly, the number of anion sites in GBM was found to decrease. The authors believe that the reduction of heparan sulfate is responsible for the increase in protein permeability in the intrinsic glomerular filtration membrane. In 1998, Karl Tryggrason et al reported that the disease has small kidney. The abnormality of nephrin on the septum of the interspinous process is caused by the mutation of the NpHSI gene encoding nephrin. As seen in the pathology, in the early stage of the disease, the glomerulus may be normal, and may also present focal segmental sclerosis, mesangial Cell and mesangial matrix hyperplasia presents diffuse tubular cystic dilatation. In the advanced stage of the disease, glomerular capillary collapses, showing diffuse sclerosis; renal tubules expand extensively, atrophy; interstitial inflammatory cell infiltration and fibrosis, Some people have said that the most characteristic change in the intrinsic is the cystic dilatation of the proximal convoluted tubule, known as "microcystic disease", but this lesion of the renal tubule is found. Can be acquired by line, due to the continued Voluminous and (or) the urinary tubules is blocked, the unit is not induced renal tubules appear fully mature cystic changes.
Prevention
Congenital nephrotic syndrome prevention
Congenital or secondary patients with this disease should actively preventive treatment and symptomatic supportive treatment, and strengthen health promotion and pregnancy care, prenatal examination, etc., to prevent the occurrence of early renal failure.
Complication
Congenital nephrotic syndrome complications Complications, edema, ascites
Mainly secondary to secondary hypothyroidism, embolism, increased blood pressure in the later period.
1. Finnish type due to rapid increase in proteinuria leading to nephrotic syndrome, severe systemic edema and ascites, often complicated by infection, thrombosis and growth and developmental disorders or renal failure, children with more than 1 year old due to complications of nephrotic syndrome such as infection Or death from kidney failure.
2. Non-Finnish patients with a small number of children can be complicated by Drash syndrome, showing male pseudohermaphroditism and/or Wilms tumor.
Symptom
Congenital nephrotic syndrome symptoms common symptoms proteinuria nephrotic syndrome corticosteroids increased venous venous thrombosis placenta large kidney yin deficiency renal failure corneal opacity nystagmus
1. Congenital nephrotic syndrome Finnish type: The disease occurs mostly in newborns. Most children have premature birth, low body weight, large placenta (average weight is 40% of neonatal weight), 50% of children at birth or week 1 Proteinuria was found inside, and the rest of the children also developed proteinuria within 3 months of birth. The proteinuria was highly selective at first, and then gradually became non-selective, often accompanied by growth and development disorders and malnutrition. Low position, special face such as collapsed nose, easy to merge umbilical hernia, convulsion, infection and renal vein thrombosis, etc. About 50% of children died of infection within 1 year old, and the rest developed renal dysfunction in 2 years old, with an average of 2.8. Years old enters end-stage renal disease, and if he does not take treatment, he will die at the age of 4.
2. Congenital nephrotic syndrome non-Finnish type: The incidence of the disease is later than that of the Finnish type. Most of the proteinuria occurs after 3 months of birth to 3 years old. The proteinuria increases with nephrotic syndrome, and the renal function damage progresses rapidly. Most children die of kidney failure in childhood, but a small number of children with milder proteinuria have a slower progression of renal function and a little later death. The disease is usually full-term, birth weight and placental size and normal delivery. No difference, a small number of children can be complicated by Drash syndrome, showing male pseudohermaphroditism and/or Wilms tumor.
3. Secondary congenital nephropathy: In addition to the clinical manifestations of nephropathy, secondary CNS is often accompanied by clinical symptoms of some unique primary diseases, which can be differentiated from primary CNS.
4. Drash syndrome: Drash syndrome manifests as congenital nephrotic syndrome, complicated by Wilms tumor and/or male pseudohermaphroditism, other related lesions such as cataract, corneal opacity, small head, strabismus, nystagmus and eye distance Excessively wide, the syndrome appears in siblings, does not respond to treatment, and can recur after renal allografts. Recurrence of post-transplant nephrotic syndrome in these patients is due to cytomegalovirus infection or transplant rejection.
Common concomitant symptoms of Drash syndrome are 46XY and ocular abnormalities in male pseudohermaphroditism. A case report of 46XY female patients has the same performance. The renal pathological manifestation of this syndrome is diffuse mesangial sclerosis, due to the high incidence of bilateral Wilms tumors. It has been suggested that preventive nephrectomy should be done.
5. Galloway-Mowat syndrome and Roos syndrome: Galloway-Mowat syndrome also manifests as congenital nephrotic syndrome. Typical renal pathology is the presence of flocs and fine filaments on the structurally distorted glomerular basement membrane. (6-8 nm) deposition.
Roos syndrome, which is characterized by small head, infantile spasm, and psychomotor block, is also a familial disease. It is often accompanied by nephrotic syndrome in infancy. The renal pathology of Roos syndrome is focal segmental. Glomerular sclerosis with extensive mesangial disintegration, vertebral epithelial dysplasia, mental retardation, conductive hearing loss and retinitis pigmentosa, also associated with focal segmental glomerulosclerosis and nephrotic syndrome in infancy Syndrome.
Examine
Examination of congenital nephrotic syndrome
ordinary inspection
1. Increased amniotic fluid AFP level: It is a characteristic change in children with FNS. Due to intrauterine proteinuria, AFP levels in amniotic fluid increase during the 16th to 22nd week of pregnancy; congenital neural tube hypoplasia can also occur in amniotic fluid AFP The level is increased, but the level of cholinesterase is often increased at the same time.
2. Urine changes: Children often have proteinuria, which can be expressed as a large amount of proteinuria and microscopic hematuria. At first, proteinuria is highly selective, and then gradually becomes non-selective.
3. Hypoproteinemia: The level of serum albumin in children with CNS is very low, usually less than 10g/L.
4. Renal insufficiency: The kidney function is normal at the beginning of the disease, but it can progress rapidly to renal failure, blood urea nitrogen, elevated creatinine and increased red blood cells.
5. Others: Secondary CNS has laboratory features of primary disease, such as congenital syphilis, positive VDRL test; Toxoplasma gondii, rubella, giant cells, hepatitis virus infection, and its antibody titer is elevated.
Kidney biopsy: Check for the following changes:
1. Light microscopy: In the early stage of the disease, the glomeruli may be normal, and may also present focal segmental sclerosis, mesangial cells and mesangial matrix hyperplasia; renal tubules exhibit cystic dilatation, in the advanced stage of the disease, kidney The glomerular capillaries collapse, showing diffuse sclerosis; the renal tubules are extensively dilated, atrophy; interstitial inflammatory cell infiltration and fibrosis, only the enlargement of the podocyte in the early stage of DMS, the fusion of the foot processes, the mesangial matrix Proliferation; in the advanced stage, most of the glomerular capillaries of the glomeruli are arranged along the vacuolar degeneration of epithelial cells, tubule atrophy, inflammatory cell infiltration, interstitial fibrosis.
2. Immunofluorescence: early normal; late in the mesangial area may have a small amount of IgM and C3 deposition, may be negative, there may be IgM, C1q, C3 deposition in the mesangial area or hardened glomerular area.
3. Electron microscopy: endothelial cell swelling, epithelial cell foot process fusion, basement membrane shrinkage, etc., the basement membrane is irregularly thickened, and the normal three-layer structure is replaced by a layer of disordered, transparent, electronic compact, visible in the basement membrane. To a large number of filamentous substances, the foot processes fuse and the mesangial matrix expands.
(1) Finnish type: The pathological examination of the kidney is characterized by a cystic dilatation of the proximal convoluted tubule. Therefore, the disease was previously named as infant microcapsule disease, early glomerular normal, and then mesangial hyperplasia, advanced glomerulus Hardening with interstitial fibrosis, electron microscopy showed diffuse foot process fusion of glomerular visceral epithelial cells, negative immunofluorescence.
(2) Non-Finnish type: renal pathology is diffuse glomerular mesangial sclerosis or focal glomerular sclerosis.
(3) secondary congenital nephropathy: with the different causes, secondary CNS often have their own characteristics in pathological changes, such as congenital syphilis infection: light microscopy often manifests as membranous or proliferative glomerulus Nephritis, occasionally accompanied by the formation of crescentic body, extensive interstitial inflammatory cell infiltration; immunofluorescence can be found in the mesangial deposition area with the presence of Treponema pallidum antigen; electron microscopy can be found along the basement membrane with small nodules dense Subendothelial deposition, as well as mercury poisoning, Toxoplasma gondii, rubella, giant cells, hepatitis virus infection often show the pathological changes of immune complex nephritis; in addition, in patients with giant cell infection, giant cell inclusion bodies can be seen in endothelial cells.
4. Others should be routinely done B-ultrasound, imaging examinations, etc.
Diagnosis
Diagnosis and diagnosis of congenital nephrotic syndrome
Diagnostic criteria
The nephrotic syndrome that occurs within 3 months of birth is congenital nephrotic syndrome.
Finnish type
(1) Clinical diagnosis: depending on whether there is a family history; there is proteinuria in the uterus, when the symptoms appear in the clinic, the albumin in the blood has been <10g/L, when the blood albumin is corrected to 15g/L, urine Medium protein can be >20g/L;
Placenta is large (> 25% of birth weight); clinical manifestations of GFR are still normal within 6 months; except for other known causes; renal biopsy has characteristic pathological changes.
(2) Prenatal diagnosis: Prenatal diagnosis is often performed by means of alpha-fetoprotein (AFP) in amniotic fluid. This test is a normal fetal protein synthesized from fetal liver, yolk sac and digestive tract. Its molecular size And the electrochemical characteristics are similar to those of albumin in blood. At 13 weeks of gestation, the concentration of fetal blood reaches a peak. When the proteinuria occurs in the fetus, AFP enters the amniotic fluid with urine protein. Therefore, pregnant women who have given birth to this disease are Detection of amniotic fluid AFP at 11 to 18 weeks of gestation may be helpful for prenatal diagnosis, but it should be noted that this protein may also be seen in children with neural tube defects, but in addition to increased AFP in amniotic fluid, biliary Alkaline esterase is also increased, can be identified, in addition, AFP can also be seen in twins, Turner syndrome and so on.
2. Non-Finnish this disease is also an autosomal recessive disease, which occurs in children between 3 months and 3 years old, and occasionally at birth or within 3 months after birth. The pathological feature is glomerular diffuseness. Mesangial sclerosis or proliferative sclerosis, focal segmental sclerosis, cystic dilatation of the renal tubules, most prominent in the deep cortex, clinically most of these children present with nephrotic syndrome, and more rapidly progress to end-stage renal disease .
3. Drash syndrome Drash syndrome manifests as congenital nephrotic syndrome, complicated by Wilms tumor and/or male pseudohermaphroditism, other related lesions such as cataract, corneal opacity, small head, strabismus, nystagmus and eye distance Wide, the syndrome often appears in siblings.
4. Secondary congenital nephropathy secondary to CNS in addition to the clinical manifestations of nephropathy, often accompanied by clinical symptoms of some unique primary diseases, can be differentiated from the primary CNS, such as congenital syphilis patients, VDRL test Positive; such as Toxoplasma gondii, rubella, giant cells, hepatitis virus infection, and its antibody titer is elevated.
Differential diagnosis
1. Finnish and non-Finnish CNS can cause primary congenital nephrotic syndrome, except for Finnish congenital nephrotic syndrome, which can be caused by non-Finnish or diffuse mesangial sclerosis. No abnormalities, normal placenta size, although the onset can also be early in the neonatal period, but more than 3 months after birth, the disease entered the kidney function earlier, died of uremia, pathological early stage of mesangial sclerosis, The glomerular capillaries collapse, there is no cell proliferation; in the later stage, glomerular sclerosis and renal tubules, interstitial fibrosis, and occasionally caused by minimal lesions, pathological changes of focal segmental sclerosis, the adrenal cortex Hormone treatment effects are the same as older children.
2. Inherited nephrotic syndrome and secondary identification of secondary CNS due to the treatment of primary disease (such as secondary treatment of syphilis) can be expected to relieve kidney disease, combined with secondary disease caused by the primary disease itself Clinical and laboratory performance, more can be clearly diagnosed, small infants have unexplained nephrotic syndrome with external genital abnormalities, should consider Drash syndrome, this sign Drash 1970 report, manifested as renal embryonal tumor (Wilms tumor), male Pseudosexual malformation and kidney involvement (which may be manifested as nephrotic syndrome); some cases have only two manifestations, and the renal pathology is diffuse mesangial sclerosis and tubular atrophy, which is lesioned in the kidney. The glomerulus of the cortical surface layer is heavier than the near medulla.
