Congenital Nephrotic Syndrome of Finnish Type - An Overview

Introduction:

Several diseases and disorders can present at the time of birth due to genetic malformations in the pregnancy period, thus complicating the quality of life of the just-born child. Such conditions can have varied manifestations and symptoms in several systems in the body. One such rare condition affecting the kidneys of a newborn child is a congenital nephrotic syndrome of the Finnish type.

What Is Congenital Nephrotic Syndrome of the Finnish Type?

Congenital nephrotic syndrome of Finnish type is a type of nephrotic syndrome caused by genetic mutations and variations. The term Finnish type is added to denote the higher prevalence in Finland. Other names for this rare nephrotic syndrome are nephrosis 1, Finnish congenital nephrosis, and congenital nephrotic syndrome 1.

What Is the Pathophysiology of Congenital Nephrotic Syndrome of Finnish Type?

The pathogenesis of congenital nephrosis is the genetic mutations involving the NPHS1 gene. NPHS1 gene is the significant gene involved in developing and maintaining a component called nephrin. Nephrin is responsible for the structural and functional integrity of the glomerular filtration membrane. The selective filtration role of the glomerular filtration membrane is achieved by the optimal functioning of nephrin. Nephrin is the component present in the slit diaphragm of the podocytes of the glomerular filtration barrier. It forms a zipper-like complex with other nephrin molecules from adjacent podocytes, thus achieving optimal filtration of large molecules (like albumin) and allowing the passage of water and other small molecules.

In congenital nephrotic syndrome of the Finnish type, this structural integrity maintained by nephrin is lost due to genetic variations. There is a significant loss in the filtration process; hence, there is excessive elimination of proteins rather than absorption. Congenital nephrotic syndrome of Finnish type occurs as an autosomal recessive inheritance where both parents must carry the mutated NPHS1 gene to cause an incidence in their offspring. Also, the incidence in the children of such parents is only 25 percent. This kind of NPHS1 genetic mutation is most commonly found in Finland people, and there are two different genes noted among them - Fin-major (a large deletion) and Fin-minor (a point mutation).

What Are the Clinical Manifestations of Congenital Nephrotic Syndrome of Finnish Type?

There is a distinct set of clinical manifestations seen in congenital nephrotic syndrome of the Finnish type. These features are noted right from birth and seen completely within the child's first three months.

• The first sign of Finnish nephrosis is severe protein elimination through the renal route (proteinuria). Proteinuria in the infant can lead to other conditions like hypoalbuminemia (reduced albumin in circulating blood) and fluid accumulation.

• The child is noted to have swelling of the face and legs. The child may appear puffy as a result of fluid accumulation in the body. This is because reduced plasma oncotic pressure secondary to hypoalbuminemia causes fluid to accumulate in various spaces in the body, like the abdominal cavity (causing ascites).

• Protein loss from the body occurs chronically, resulting in reduced or poor growth. The infant usually fails to thrive in this condition.

• Other than albumin, immunoglobulins can be removed through urine. Excretion of immunoglobulin proteins causes infants with Finnish nephrosis to develop infections very frequently.

• There can be an imbalance in the amount of clotting factors present in the circulating blood. So, such infants are hypercoagulable, where the incidence of blood clots and emboli formation is always high.

• Urinary excretion of thyroid-binding globulin can cause the infant to develop hypothyroidism, for which a lifelong hormone treatment with thyroxine may be necessary.

• Vitamin D is lost through urine, and infants develop rickets due to a vitamin D deficiency.

• As a compensatory mechanism of the body for hypoalbuminemia, the liver tries to secrete more lipids into the circulating bloodstream to combat the low albumin levels. This causes hyperlipidemia in infants with congenital nephrotic syndrome of the Finnish type.

• Respiratory distress occurs as a complication of pleural effusion secondary to hypoalbuminemia in such infants.

How to Diagnose Congenital Nephrotic Syndrome of Finnish Type?

A clinical physical examination will explain a lot of features that point toward congenital nephrotic syndrome of the Finnish type. The babies may show an edematous figure with poor development. Swelling may be palpable, especially in the abdominal area, pointing to ascites.

• A huge amount of protein is excreted in the urine, as can be evident from analyzing urine samples.

• Hematological laboratory investigations show reduced albumin in the circulation. A low albumin level acts as a diagnostic marker during laboratory investigations.

• Cholesterol and triglyceride levels may be in the peak range in affected infants.

• Since kidney function is sparse, a significant electrolyte imbalance will occur in the infant within three months of birth.

• Thyroid function tests will be performed on the infant to know about the state of hypothyroidism.

• Vitamin D levels in the serum will be detected to identify rickets in the growing infants.

• Genetic testing is the confirmatory test to diagnose congenital nephrotic syndrome of Finnish type. This procedure looks for genetic mutations in the NPHS1 gene, which codes for nephrin components. A detailed family history, genetic counseling, and amniocentesis can elicit the incidence of congenital Finnish nephrosis in the prenatal period.

A kidney biopsy may be necessary to determine the extent of kidney damage in this syndrome. However, a kidney biopsy is not a mandatory procedure in diagnosing congenital nephrotic syndrome of the Finnish type.

How to Manage Congenital Nephrotic Syndrome of Finnish Type?

• Due to a hefty protein loss, infants require a high-protein diet supplemented with albumin infusions to maintain plasma oncotic pressure. Parenteral nutrition may be necessary for those with severe gastrointestinal involvement.

• As developing infants are highly susceptible to infections, prophylactic use of antibiotics will be suggested.

• Other medications prescribed to babies with congenital Finnish nephrosis include diuretics (for edema), thyroxine hormone (for hypothyroidism), vitamin D supplements, anticoagulants (to prevent thrombosis), and renal replacement therapy if required.

The definitive treatment for Finnish nephrosis is kidney transplantation after the child has reached an optimal weight of about eight to ten kilograms.

Conclusion:

Congenital nephrotic syndrome (Finnish type) is a perilous genetic disorder that affects babies right from birth. Research is needed to target the gene responsible for the causation of this syndrome. Without treatment, the prognosis of congenital nephrotic syndrome of the Finnish type is poor and can be a fatal condition.