Congenital nephrotic syndrome

Overview

Congenital Nephrotic Syndrome (CNS) is a rare kidney disorder that typically presents within the first three months of life. It is characterized by heavy proteinuria (excess protein in the urine), hypoalbuminemia (low blood albumin levels), edema (swelling), and hyperlipidemia (elevated blood lipids). These features result from damage to the glomeruli, the filtering units of the kidneys. CNS is most often genetic in origin and can lead to life-threatening complications without early intervention. The Finnish type of CNS is the most well-known form and is especially prevalent in Finland, though other genetic subtypes exist globally.

Causes

Congenital Nephrotic Syndrome is usually caused by mutations in genes critical to kidney filtration. The most common genetic causes include:

• NPHS1 gene: Associated with the Finnish type of CNS; this gene encodes nephrin, a key protein in the glomerular filtration barrier

• NPHS2 gene: Encodes podocin; associated with steroid-resistant nephrotic syndrome and CNS in some cases

• WT1 gene: Mutations may lead to syndromic forms of nephrotic syndrome (e.g., Denys-Drash syndrome)

• LAMB2 gene: Mutations cause Pierson syndrome, a severe form of CNS with eye abnormalities

The condition is inherited in an autosomal recessive manner, meaning a child must inherit two defective copies of the gene (one from each parent) to develop the disease.

Symptoms

Symptoms of CNS typically appear shortly after birth or within the first few months of life. Key features include:

• Severe edema: Generalized swelling, especially around the eyes, abdomen, and limbs

• Massive proteinuria: Excessive loss of protein in urine

• Hypoalbuminemia: Low blood albumin due to urinary loss

• Hyperlipidemia: Elevated cholesterol and triglyceride levels

• Failure to thrive: Poor weight gain and growth

• Frequent infections: Due to protein loss impairing the immune system

• Enlarged placenta: Often seen prenatally in the Finnish type

• Prematurity and low birth weight

In severe cases, complications may include thromboembolism, hypothyroidism, and acute kidney injury.

Diagnosis

Diagnosis of Congenital Nephrotic Syndrome involves a combination of clinical evaluation, laboratory tests, and genetic analysis. Diagnostic steps include:

• Urinalysis: Detects heavy proteinuria

• Blood tests: Show hypoalbuminemia, hyperlipidemia, and impaired kidney function

• Renal ultrasound: May reveal enlarged kidneys

• Genetic testing: Confirms specific gene mutations associated with CNS

• Kidney biopsy: Sometimes performed to assess the extent of glomerular damage (used cautiously in infants)

• Prenatal screening: Elevated alpha-fetoprotein (AFP) levels in amniotic fluid or maternal blood may suggest CNS

Treatment

There is no cure for CNS, so treatment focuses on managing symptoms, minimizing complications, and ultimately preparing for kidney transplantation. Treatment strategies include:

• Albumin infusions: To correct hypoalbuminemia and reduce edema

• Diuretics: To control fluid overload

• ACE inhibitors or NSAIDs: To reduce protein loss in urine

• Anticoagulants: To prevent blood clots in high-risk patients

• Thyroid hormone replacement: If hypothyroidism develops due to protein loss

• Antibiotics and vaccination: To manage and prevent infections

• Nutritional support: High-protein, calorie-dense feeding plans

• Dialysis: Often required before transplantation in progressive cases

• Kidney transplantation: The definitive treatment for long-term management, often performed in early childhood

Prognosis

The prognosis for infants with Congenital Nephrotic Syndrome depends on the severity and underlying genetic cause. Without treatment, CNS can lead to life-threatening complications within the first years of life. However, with aggressive medical management and early kidney transplantation, survival and quality of life have improved significantly. Lifelong monitoring and immunosuppressive therapy (post-transplant) are essential. Early diagnosis, genetic counseling, and coordinated care with nephrology specialists are key to optimizing outcomes.