Congenital Nephrotic Syndrome

Congenital nephrotic syndrome is diagnosed at or soon after birth.  It can have one of several causes, the most common, though all are rare, of the rare different types is
congenital nephrotic syndrome of the Finnish type, named such because it is
more common in Finland than anywhere in the world.

As I think many of you know, nephrotic syndrome is a group of signs and
symptoms and not a diagnosis in itself.    It consists of 1) losing a large
amount of protein in the urine (proteinuria or albuminuria), so that 2) blood
protein levels, especially albumin, which is a small protein, are low
(hypoproteinemia or hypoalbuminemia, 3) swelling (edema) results, and 4) blood
cholesterol levels are high.    The small blood vessels are not water tight,
and what keeps water in the blood vessels is the sponge-like effect of protein
(mainly of albumin), which is called oncotic pressure.    The defect   that
starts it all is in the kidney filters, where something goes wrong and they
allow protein to leak into the urine and the cascade starts.  In most of the
acquired forms of nephrotic syndrome, like minimal change disease and focal
sclerosis, something is wrong in the interaction of the kidney filter
(glomerulus) and the immune system.  In the genetic forms of congenital
nephrotic syndrome, something is wrong with the chemical structure of the
filters (glomeruli) and the disease is not amenable to treatment with
medication.   

Congenital nephrotic syndrome has several causes.  It can be the result of an
in-utero infection such as cytomegalovirus (CMV), toxoplasmosis, or syphilis,
or, it can be the result of a genetic disease, congenital nephrotic syndrome
of the Finnish type or diffuse mesangial sclerosis.  Both of these are usually
autosomal recessive diseases, meaning that it takes a gene from each parent to
transmit the disease.   Therefore each child of parents who carry the disease
has a 25% chance with each child that the child will have the disease. 

The course of the genetic disease is nephrotic syndrome which is severe, with
heavy losses of protein that don't stop, and then over time, generally by 4
years of age, renal failure develops that goes to end stage renal disease,
necessitating dialysis and/or transplantation.

Until renal failure becomes a problem, nephrotic syndrome is a problem, with
losses of many critical proteins, including vitamin D binding protein, thyroid
binding protein, immunoglobulins (ie gammaglobulins that are key proteins in
preventing infection).   Vitamin D binding protein carries vitamin D with it,
so that it needs to be replaced.   Thyroid binding protein carries with it
thyroid hormone, so that it also needs to be replaced.    Nutrition is also a
problem with the losses of many important proteins, so putting this all
together the management of an infant/child with congenital nephrotic syndrome
in the nephrotic phase is a challenge because of the heavy loss of many
important proteins.

One approach is the removal of one kidney, which cuts the loss of proteins by
taking one of two kidneys away that can lose protein.   This especially makes
sense since you know that renal failure will ensue in time in any case.

ACE inhibitors (angiotensin converting enzyme inhibitors) are also used to cut
down the loss of proteins in the urine.