What is Congenital Nephrotic Syndrome?
Congenital nephrotic syndrome (CNS) is a condition that is identified when signs become evident within the first three months after a baby is born. This involves having too much protein in the urine, swelling, low levels of albumin and gamma globulins in the blood, an increased tendency for blood clotting, and high levels of fats in the blood. If similar symptoms develop between 4 to 12 months of age, it’s referred to as infantile nephrotic syndrome. On the other hand, if these symptoms occur after the age of one, it’s called childhood nephrotic syndrome.
What Causes Congenital Nephrotic Syndrome?
Congenital nephrotic syndrome, a rare kidney disorder in children, can be caused by different factors. These can be split into three categories: genetic, infectious, and non-genetic causes.
Genetic causes might include defects in certain genes, such as NPHS1, NPHS2, WT1, PLCE1, and LAMB2.
Infectious causes could be due to infectious diseases that a child contracts before they’re born, such as syphilis, toxoplasmosis, cytomegalovirus, HIV, Hepatitis B virus, or rubella.
Non-genetic causes might include factors like mercury poisoning, a blockage in a kidney vein, or issues related to the mother’s immune system, such as lupus.
Most of the time, congenital nephrotic syndrome is caused by a genetic problem that affects the protein structures handling the filtration process in the kidneys.
The most common form of this is called congenital nephrotic syndrome of the Finnish type (CNF) named so because it’s quite common in Finland. It’s a condition passed down through families where a mutation in the NPHS1 gene affects nephrin, a protein that plays a role in kidney filtration. Because the NPHS1 gene only functions in cells of the kidney (called podocytes), children with the Finnish type of this syndrome only have issues related to the kidneys.
Risk Factors and Frequency for Congenital Nephrotic Syndrome
Congenital nephrotic syndrome is a rare condition that affects 1 to 3 out of every 100,000 newborns. One particular type known as Congenital nephrotic syndrome of the Finnish type, or CNF, is more common in Finland, affecting 1 out of every 8,200 births.
Signs and Symptoms of Congenital Nephrotic Syndrome
The history and physical examination of a patient might reveal symptoms of a condition that could be related to a variety of issues. These could include factors from before and shortly after birth, family history, the patient’s own history, and physical signs observed by a doctor.
- Prenatal and perinatal history: Placenta weight lower than 25% of newborn’s weight, unusually large clear space in the tissue at the back of an unborn baby’s neck (enlarged prenatal nuchal translucency), swelling within the baby (fetal edema), high levels of a specific protein (alpha-fetoprotein) in the amniotic fluid, and low amniotic fluid (oligohydramnios).
- Family history: Past instances of a kidney disease present from birth (congenital nephrotic syndrome), marriages between relatives (consanguinity), specific ethnic backgrounds, early infant deaths, neurological and kidney diseases seen during infancy.
- Patient history: Swelling across the body and poor growth.
- Physical examination: Signs of swelling in specific parts of the body such as around the heart (pericardial), around the lungs (pleural effusions), and in the abdomen (ascites).
Testing for Congenital Nephrotic Syndrome
Congenital nephrotic syndrome of the Finnish type, a rare kidney disease, can be detected before a baby is born when the mother has higher than normal levels of alfa fetoprotein in her blood during the second trimester of pregnancy.
Initially, there may not be changes in the thyroid-stimulating hormone (TSH) levels. But, in most cases, it begins to increase during the first month post birth. Along with this, free thyroxine (T4), another hormone from the thyroid gland, is usually lower than normal.
Several blood tests may be part of the evaluation, measuring things like blood count, along with levels of sodium, chloride, magnesium, protein, albumin, creatinine, urea, cholesterol, fasting triglycerides, and glucose.
The doctor may also review:
– The level of Serum IgG, another type of protein found in our blood.
– Levels of phosphate, ionized calcium, vitamin D3, alkaline phosphatase, and PTH.
– Urea and creatinine levels may vary, with kidney function usually staying normal for the first few months.
– Lower than normal albumin levels and thyroid hormone levels.
– A urine test will reveal high protein levels, blood cells, and white blood cells with no signs of infection.
– An ultrasound can show if the kidneys are of normal size or larger and if the kidney cortex is producing strong echoes.
– A heart ultrasound might be done to check for abnormalities like fluid around the heart and increased left ventricular mass.
A kidney biopsy can also provide useful information. It may reveal dilation of the proximal tubules, increased number of cells in the mesangial region, and a mild increase in mesangial matrix. In a detailed analysis called electron microscopy, it can be seen that the foot-like extensions of podocyte cells are flattened.
However, for an accurate diagnosis of congenital nephrotic syndrome of the Finnish type, a genetic analysis is the best option, where doctors check for mutations in the NPHS1 gene.
Treatment Options for Congenital Nephrotic Syndrome
The treatment goals for congenital nephrotic syndrome, a kidney disorder present at birth, include controlling fluid build-up, preventing and treating potential complications such as infections and clot forming, and ensuring the child receives enough nutrition for growth. Kidney transplantation is typically the only cure.
To replace the large amount of protein lost through urine, which can cause severe complications like undernourishment, fluid build-up, and growth challenges, patients receive albumin infusions. This treatment involves supplying the body with albumin, a protein normally found in the blood, through central venous catheters. This is usually done with a 20% albumin solution along with furosemide, another medicine that treats fluid build-up, with both given at a specific dosage.
Several medications are also used in the treatment of congenital nephrotic syndrome. This includes angiotensin-converting enzyme (ACE) inhibitors and indomethacin, which help reduce the amount of protein excreted in urine. Additionally, thyroxine, a hormone that can improve low thyroid function typically seen in these patients, is also administered. The dosage is initially set and then adjusted based on individual hormone levels.
To manage the risk of developing blood clots due to protein loss in urine, patients are also given anticoagulation therapy. Medications such as aspirin and dipyridamole are typically recommended for this purpose.
Patients are advised to follow a diet high in energy (130 calories per kilogram per day) and protein (3 to 4 grams per kilogram per day). The first sources of these nutrients should ideally be breast milk or milk formulas. Necessary dietary supplements may include a specific type of protein, a blend of certain oils, and doses of Vitamin D, magnesium, and calcium.
In some cases, removal of one or both kidneys may be conducted to reduce protein loss and decrease the need for albumin infusions. Once the child reaches a certain weight, the diseased kidneys are removed, and the patient is put on peritoneal dialysis, a treatment that uses the body’s natural filters to clean the blood. The ultimate goal, however, is to perform a kidney transplant when the child has grown enough, usually at 1 to 2 years of age. Different approaches may be taken for the transplant, depending on the child’s condition and the doctor’s preferences.
What else can Congenital Nephrotic Syndrome be?
Congenital Nephrotic Syndrome, a kidney condition in infants, has many types. They are divided into either those passed on by any parent (autosomal dominant) or those that need two carrier parents (autosomal recessive). Each type involves different genes and proteins that influence how this condition shows up, with symptoms varying widely.
Some conditions that can trigger this syndrome include:
- Denys-Drash syndrome: This includes effects such as abnormal sexual development in males, a specific type of kidney tumor (Wilms tumor), and rapid onset nephrotic syndrome leading to kidney failure. These issues often show up on a biopsy as diffuse mesangial sclerosis.
- Frasier syndrome: This is usually recognized by symptoms like glomerulopathy (a kind of kidney disease), abnormally developed sexual organs in males, and gonadoblastomas (tumors that develop in gonads). The disease progresses slower to end-stage kidney disease than Denys-Drash syndrome.
- Pierson’s syndrome: This is known by newborn nephrotic syndrome, tiny pupils, visual challenges, and low muscle tone. Unfortunately, children with Pierson syndrome often pass away due to kidney failure within days or weeks after birth.
- Nail-patella syndrome: Symptoms can range from irregular or missing fingernails and toenails, small or missing kneecaps, and kidney problems that can lead to chronic kidney disease.
- Galloway Mowat syndrome: This is notably recognized by a small head, abnormalities in the brain, and early onset nephrotic syndrome. Other signs can include small eyes, a narrow forehead, and a high-arched palate.
Some infections like congenital syphilis, toxoplasmosis, or viral infections such as cytomegalovirus can also cause congenital nephrotic syndrome. The good news is these are usually treatable and have a good prognosis!
Other potential causes of congenital nephrotic syndrome are originating from reactions to fetal cells in the mother that lead to neonatal alloimmunization, blockage of the kidney veins, lupus in mother, and poisoning from mercury.
What to expect with Congenital Nephrotic Syndrome
The congenital nephrotic syndrome of the Finnish type is a condition that worsens over time and usually results in severe kidney disease by the time a child is 2-3 years old. The outlook can be more severe if the condition is caused by mutations in the NPHS1 gene compared with the NPHS2 gene. Additionally, the prognosis varies among patients of different ethnic backgrounds. Interestingly, female patients with NPHS1 mutations tend to live longer than male patients.
The only treatment that can cure this syndrome in most cases is a kidney transplant. Fortunately, the transplant outcomes for this syndrome are generally quite positive. The survival rate for patients after five years is over 90%, and over 80% of the transplanted kidneys continue to function properly.
Possible Complications When Diagnosed with Congenital Nephrotic Syndrome
Congenital nephrotic syndrome is a condition that makes individuals more prone to infections from encapsulated organisms like Haemophilus influenzae, Escherichia coli, and Streptococcus. This happens because essential components of the body’s defenses are lost in the urine.
Patients with this condition also have an elevated risk of developing blood clots (thromboembolism) because of the loss of an important blood protein via urine and increased production of clot-promoting factors by the liver. The types of blood clots one might get include central sinus thrombosis, deep vein thrombosis, renal vein thrombosis, and lung clots (pulmonary embolism).
Other problems associated with this syndrome include failure to grow at a normal rate, protein malnutrition, and vitamin deficiency. It can also result in low levels of thyroid hormone (thyroxin) and a serum protein responsible for transporting thyroid hormones due to excessive protein excretion.
Problems associated with this syndrome include:
- Increased susceptibility to infections
- Higher risk of various types of blood clots
- Failure to grow at a normal rate
- Protein malnutrition and vitamin deficiency
- Low levels of thyroid hormone and serum thyroid-transporting proteins
