Congenital nephrotic syndrome
Encyclopedia
Congenital nephrotic syndrome is an inherited disorder characterized by protein
in the urine
and swelling of the body.
. It occurs predominantly in families of Finnish
origin and manifests shortly after birth. It is an inherited disorder. The condition is caused by a defect in the protein nephrin
, which is found in the kidney
.
Protein
s and fat
s are excreted in the urine, and there is an abnormally high fat level in the blood. Swelling occurs due to kidney failure, combined with the loss of blood protein. This is because proteins in the blood normally keep fluids in the blood stream, and when protein level is low, the fluid can leak into the body tissues.
Some of the proteins lost in the urine are immune system
antibodies
that fight infections. The disorder commonly results in infection, malnutrition
, and kidney failure. It can often lead to death by 5 years of age.
. Abnormal sounds are heard when listening to the heart
and lungs with a stethoscope
. Blood pressure
may be high. The patient may have signs of malnutrition
.
A urinalysis
reveals large amounts of protein and the presence of fat in the urine. Total protein in the blood may be low. The disorder can be screened for during pregnancy
by finding elevated levels of alpha-fetoprotein
on a routine sampling of amniotic fluid
. Genetic tests should be used to confirm the diagnosis, if the screening test is positive.
CNF is one of the Finnish heritage disease
s. By use of positional cloning strategies, Kestila et al. isolated the gene responsible for NPHS1. Mutations in Finnish patients with NPHS1 were found in this gene, which they termed nephrin. The most common Finnish mutation was a deletion of 2 nucleotides in exon 2 (602716.0001), resulting in a frameshift and a truncated protein. The predicted nephrin protein belongs to the immunoglobulin family of cell adhesion molecules and is specifically expressed in renal glomeruli. It was also observed that, in most cases, alleles typically found on CNF chromosomes of Finnish families were also found on CNF chromosomes of non-Finnish families from North America and Europe.
Frequent infection
s may occur over the course of the disease.
medications help rid the body of excess fluid. ACE inhibitor
medications (like Captopril
and others) and non-steroidal anti-inflammatory drugs (like indomethacin) are used to slow the spilling of protein
in the urine. Antibiotics may be needed to control infections.
Dietary modifications may include the restriction of sodium
and use of dietary supplement
s as appropriate for the nature and extent of malnutrition
. Fluids may be restricted to help control swelling.
Removal of the kidney
s, dialysis
, and kidney transplant may be recommended.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
and swelling of the body.
Causes
Congenital nephrotic syndrome is a very rare form of nephrotic syndromeNephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
. It occurs predominantly in families of Finnish
Finland
Finland , officially the Republic of Finland, is a Nordic country situated in the Fennoscandian region of Northern Europe. It is bordered by Sweden in the west, Norway in the north and Russia in the east, while Estonia lies to its south across the Gulf of Finland.Around 5.4 million people reside...
origin and manifests shortly after birth. It is an inherited disorder. The condition is caused by a defect in the protein nephrin
Nephrin
Nephrin is a protein necessary for the proper functioning of the renal filtration barrier. The renal filtration barrier consists of fenestrated endothelial cells, the glomerular basement membrane, and the podocytes of epithelial cells...
, which is found in the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
.
Protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s and fat
Fat
Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
s are excreted in the urine, and there is an abnormally high fat level in the blood. Swelling occurs due to kidney failure, combined with the loss of blood protein. This is because proteins in the blood normally keep fluids in the blood stream, and when protein level is low, the fluid can leak into the body tissues.
Some of the proteins lost in the urine are immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
that fight infections. The disorder commonly results in infection, malnutrition
Malnutrition
Malnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
, and kidney failure. It can often lead to death by 5 years of age.
Symptoms
- Low birth weight
- Large placentaPlacentaThe placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
- Swelling (total body)
- Decreased urine output
- Foamy appearance of urine
- Poor appetite
- Cough
Diagnosis
An examination reveals massive fluid retention and generalized swellingSwelling (medical)
In medical parlance, swelling is the transient enlargement or protuberance in the body and may include tumors. According to cause, it may be congenital, traumatic, inflammatory, neoplastic or miscellaneous....
. Abnormal sounds are heard when listening to the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
and lungs with a stethoscope
Stethoscope
The stethoscope is an acoustic medical device for auscultation, or listening to the internal sounds of an animal body. It is often used to listen to lung and heart sounds. It is also used to listen to intestines and blood flow in arteries and veins...
. Blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
may be high. The patient may have signs of malnutrition
Malnutrition
Malnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
.
A urinalysis
Urinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
reveals large amounts of protein and the presence of fat in the urine. Total protein in the blood may be low. The disorder can be screened for during pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
by finding elevated levels of alpha-fetoprotein
Alpha-fetoprotein
Alpha-fetoprotein is a protein that in humans is encoded by the AFP gene....
on a routine sampling of amniotic fluid
Amniotic fluid
Amniotic fluid or liquor amnii is the nourishing and protecting liquid contained by the amniotic sac of a pregnant woman.- Development of amniotic fluid :...
. Genetic tests should be used to confirm the diagnosis, if the screening test is positive.
CNF is one of the Finnish heritage disease
Finnish heritage disease
A Finnish heritage disease is a genetic disease or disorder that is part of the Finnish disease heritage. Finnish heritage diseases are significantly more common in people whose ancestors were ethnic Finns, natives of Finland and Sweden. About 40 rare diseases are regarded as Finnish heritage...
s. By use of positional cloning strategies, Kestila et al. isolated the gene responsible for NPHS1. Mutations in Finnish patients with NPHS1 were found in this gene, which they termed nephrin. The most common Finnish mutation was a deletion of 2 nucleotides in exon 2 (602716.0001), resulting in a frameshift and a truncated protein. The predicted nephrin protein belongs to the immunoglobulin family of cell adhesion molecules and is specifically expressed in renal glomeruli. It was also observed that, in most cases, alleles typically found on CNF chromosomes of Finnish families were also found on CNF chromosomes of non-Finnish families from North America and Europe.
Frequent infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s may occur over the course of the disease.
Treatment
Early and aggressive treatment is required to control the disorder. DiureticDiuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
medications help rid the body of excess fluid. ACE inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
medications (like Captopril
Captopril
Captopril is an angiotensin-converting enzyme inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first ACE inhibitor developed and was considered a breakthrough both because of its novel mechanism of action and also because of the...
and others) and non-steroidal anti-inflammatory drugs (like indomethacin) are used to slow the spilling of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
in the urine. Antibiotics may be needed to control infections.
Dietary modifications may include the restriction of sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
and use of dietary supplement
Dietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
s as appropriate for the nature and extent of malnutrition
Malnutrition
Malnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
. Fluids may be restricted to help control swelling.
Removal of the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s, dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
, and kidney transplant may be recommended.
Prognosis
Many cases are fatal within the first year. Congenital nephrotic syndrome may be successfully controlled in some cases with early and aggressive treatment, including early kidney transplantation.Complications
- Frequent, severe infections
- MalnutritionMalnutritionMalnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
and related diseases - Blood clots
- Acute kidney failure
- Chronic kidney failure
- End-stage kidney disease