Congenital nephrotic syndrome (CNS) is a rare kidney disorder that manifests within the first three months of a baby’s life. This condition stems from a malfunction in the kidneys’ filtering units, known as glomeruli. These specialized structures are designed to keep essential proteins within the bloodstream while removing waste products. In CNS, the glomeruli are defective, leading to a significant leakage of protein from the blood into the urine. This excessive protein loss results in severe, widespread swelling, often visible around the eyes, in the limbs, and in the abdomen.
Causes and Genetic Basis
Congenital nephrotic syndrome is almost always a genetic condition, meaning it is inherited. It typically follows an autosomal recessive inheritance pattern, where a child develops the condition only if they receive a mutated gene copy from both parents. These parents are usually carriers, meaning they possess one copy of the faulty gene but do not exhibit symptoms themselves.
The most recognized form of CNS is the “Finnish type,” which accounts for 40% to 80% of cases and is caused by mutations in the NPHS1 gene. This gene provides instructions for making nephrin, a protein crucial for the structure and function of the kidney’s filtration barrier. A defect in nephrin impairs the formation of normal slit diaphragms, causing proteins to abnormally pass into the urine.
Other genes can also lead to CNS, including NPHS2, which codes for the protein podocin. Podocin, like nephrin, is located in the podocytes and plays a role in the slit diaphragm’s integrity and function. Mutations in NPHS2 are considered the most frequent cause of CNS in non-Finnish populations.
Signs and Diagnosis
Identifying congenital nephrotic syndrome often begins with observable signs shortly after birth. Infants typically present with severe generalized swelling, medically termed edema, which can be particularly noticeable around the eyes, in the legs, and within the abdominal cavity, known as ascites. Another common indication is a large placenta at birth. Parents might also observe frothy or foamy-appearing urine due to the high protein content, along with poor feeding and a failure to gain weight.
The diagnostic process involves several tests to confirm the condition. Urine analysis is performed to detect massive levels of protein, a hallmark of CNS. Blood tests reveal significantly low protein levels, specifically hypoalbuminemia, indicating the extensive loss of albumin from the blood. These tests help to quantify the severity of protein leakage and its systemic effects.
A definitive diagnosis is most often achieved through genetic testing, which can pinpoint the specific gene mutation responsible for the condition. This identification of genetic errors, such as those in NPHS1 or NPHS2, can often make a kidney biopsy unnecessary for diagnosis. In some cases, elevated levels of alpha-fetoprotein in amniotic fluid can also suggest the disorder during pregnancy, prompting further genetic confirmation.
Treatment Approaches
Treatment for congenital nephrotic syndrome is comprehensive and typically unfolds in distinct phases. Initially, medical management focuses on supportive care to alleviate symptoms. This involves frequent intravenous (IV) albumin infusions to replace the substantial protein lost in the urine, which helps to temporarily reduce the severe swelling. Diuretics are also administered to assist the body in excreting excess fluid buildup.
Medications to prevent blood clots are often included in the treatment plan, as children with CNS face an elevated risk of thrombosis due to protein loss. Nutritional support is also a significant aspect of initial care, often involving high-calorie formulas to counteract malnutrition and support healthy growth and development. A feeding tube might be necessary to ensure adequate nutrient intake for the infant.
For most forms of CNS, particularly the Finnish type, the native kidneys cannot be repaired and will eventually need to be removed through a procedure called bilateral nephrectomy. After the kidneys are removed, the infant requires dialysis to filter waste products from the blood and maintain fluid balance. This dialysis treatment continues until the child grows large enough and is deemed suitable for a kidney transplant, which is the definitive treatment for the condition.
Managing Complications and Long-Term Outlook
Infants with congenital nephrotic syndrome face several severe complications before their kidneys can be removed. They are at a particularly high risk of life-threatening infections because the loss of immune proteins in the urine compromises their immune system. Blood clots, or thrombosis, are another serious concern due to protein leakage. Severe malnutrition, often described as failure to thrive, is also common because of continuous protein loss and the body’s increased metabolic demands.
The long-term outlook for children with CNS is generally positive following a successful kidney transplant. After transplantation, children can typically grow, develop, and lead full, active lives. However, they will require lifelong immunosuppressant medication to prevent the body from rejecting the transplanted kidney. This ongoing medical monitoring and adherence to medication are necessary to maintain the health of the transplanted organ and ensure the child’s continued well-being.