Congenital nephrotic syndrome
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|Congenital nephrotic syndrome|
|Classification and external resources|
Congenital nephrotic syndrome is a very rare form of nephrotic syndrome. It occurs predominantly in families of Finnish origin and manifests shortly after birth. It is an inherited disorder. The condition is caused by a defect in the protein nephrin, which is found in the kidney.
Proteins and fats are excreted in the urine, and there is an abnormally high fat level in the blood. Swelling occurs due to kidney failure, combined with the loss of blood protein. This is because proteins in the blood normally keep fluids in the blood stream, and when protein level is low, the fluid can leak into the body tissues.
- Low birth weight
- Large placenta
- Swelling (total body)
- Decreased urine output
- Foamy appearance of urine
- Poor appetite
An examination reveals massive fluid retention and generalized swelling. Abnormal sounds are heard when listening to the heart and lungs with a stethoscope. Blood pressure may be high. The patient may have signs of malnutrition.
A urinalysis reveals large amounts of protein and the presence of fat in the urine. Total protein in the blood may be low. The disorder can be screened during pregnancy by finding elevated levels of alpha-fetoprotein on a routine sampling of amniotic fluid. Genetic tests should be used to confirm the diagnosis, if the screening test is positive.
CNF is one of the Finnish heritage diseases. By use of positional cloning strategies, Kestila et al. isolated the gene responsible for NPHS1. Mutations in Finnish patients with NPHS1 were found in this gene, which they termed nephrin. The most common Finnish mutation was a deletion of 2 nucleotides in exon 2 (602716.0001), resulting in a frameshift and a truncated protein. The predicted nephrin protein belongs to the immunoglobulin family of cell adhesion molecules and is specifically expressed in renal glomeruli. It was also observed that, in most cases, alleles typically found on CNF chromosomes of Finnish families were also found on CNF chromosomes of non-Finnish families from North America and Europe.
Frequent infections may occur over the course of the disease.
Early and aggressive treatment is required to control the disorder. Diuretic medications help rid the body of excess fluid. ACE inhibitor medications (like Captopril and others) and non-steroidal anti-inflammatory drugs (like indomethacin) are used to slow the spilling of protein (albumin) in the urine. Antibiotics may be needed to control infections. Patients may also take iron supplements, potassium chloride, thyroxine and other vitamins to replenish what minerals the kidneys have leaked out.
Most patients will undergo regular and frequent albumin infusion (often daily) to replace what kidneys have lost. Infusions are performed via IV so a central venous catheter will need to be surgically inserted into patients chest or groin.
Many patients have a gastrostomy tube (g-tube) inserted for medication and/or feeds. Some patients develop oral aversions and will use the tube for all feeds. Other patients eat well and only use the tube for medicine or supplemental feeds. The tube is also useful for patients needing to drink large amounts of fluids around the time of transplant.
Congenital nephrotic syndrome can be successfully controlled with early diagnosis and aggressive treatment including albumin infusions, nephrectomy, medications and ultimately a kidney transplant. Most children live fairly normal life post-transplant but will spend significant time hospitalised pre-transplant and have numerous surgeries to facilitate treatment.
Due to the protein (albumin) losses many patients have reduced muscle tone and may experience delays in certain physical milestones such as sitting, crawling and walking. Similarly many patients experience growth delays due to protein loss. Delays vary from mild to significant but most patients experience growth spurts once they receive their transplanted kidney. Physical therapy may be useful for the child to strengthen muscle tone.
Undiagnosed cases are often fatal in the first year due to blood clots, infections or other complications.
- Frequent, severe infections
- Malnutrition and related diseases
- Blood clots
- Acute kidney failure
- Chronic kidney failure
- End-stage kidney disease
- Kestilä M, Männikkö M, Holmberg C, Tryggvason K, Peltonen L (February 1994). "Congenital nephrotic syndrome of the Finnish type is not associated with the Pax-2 gene despite the promising transgenic animal model". Genomics. 19 (3): 570–2. doi:10.1006/geno.1994.1109. PMID 8188301.
- Online Mendelian Inheritance in Man (OMIM) NEPHROSIS 1, CONGENITAL, FINNISH TYPE; NPHS1 -256300
- OMIM: 256300 Congenital nephrotic syndrome, Finnish type; Congenital nephrotic syndrome 1 at NIH's Office of Rare Diseases
- OMIM: 609049 Pierson syndrome; Microcoria and congenital nephrotic syndrome at NIH's Office of Rare Diseases