Congenital nephrotic syndrome Finnish type

Other Names: Nephrosis 1, congenital, Finnish type; Congenital nephrotic syndrome 1; Nephrosis, congenital; Finnish congenital nephrosis; NPHS1; CNF

Congenital nephrotic syndrome Finnish type is a genetic condition of the kidney that begins early in development during pregnancy or within the first three months of life. The syndrome is characterized by a group of symptoms, including protein in the urine (proteinuria), low blood protein levels, high cholesterol levels, and swelling (nephrotic syndrome), which progresses rapidly to end-stage kidney disease.

Epidemiology

Congenital nephrotic syndrome affects 1 to 3 per 100,000 children worldwide. In Finland, where this condition is particularly common, congenital nephrotic syndrome is estimated to affect 1 in 10,000 children.

Cause

Congenital nephrotic syndrome Finnish type is caused by mutations in the NPHS1 gene.

These gene provide instructions for making proteins that are found in the kidneys. Specifically, the proteins produced from the NPHS1 gene are found in cells called podocytes, which are located in specialized kidney structures, called glomeruli, that filter the blood. The proteins are found at the podocyte cell surface in the area between two podocytes called the slit diaphragm. The slit diaphragm is known as a filtration barrier because it captures proteins from blood so that they remain in the body while allowing other molecules like sugars and salts to be excreted in urine. The proteins produced from the NPHS1 gene also help relay cell signals.

Mutations in the NPHS1 gene result in a decrease or absence of functional protein, which impairs the formation of normal slit diaphragms. Without a functional slit diaphragm, more molecules pass through the kidneys abnormally and get excreted in urine, including proteins and blood cells. The filtering ability of the kidneys worsens from birth, eventually leading to end-stage renal disease.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

The syndrome is characterized by a group of symptoms, including protein in the urine (proteinuria), low blood protein levels, high cholesterol levels, and swelling (nephrotic syndrome), which progresses rapidly to end-stage kidney disease. Infants with congenital nephrotic syndrome may have failure to thrive and frequent infections.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Abnormal renal tubule morphology
• Delayed eruption of permanent teeth(Delayed eruption of adult teeth)
• Elevated amniotic fluid alpha-fetoprotein
• Nephrotic syndrome
• Proteinuria(High urine protein levels)

Treatment

At this time, kidney transplantation seems to be the only treatment available for this condition.

NIH genetic and rare disease info

• NIH info on Congenital nephrotic syndrome Finnish type

Congenital nephrotic syndrome Finnish type is a rare disease.