Dense deposit disease

Dense deposit disease is a condition that primarily affects kidney (renal) function. The signs and symptoms usually appear between the ages of 5 and 15, although they can also begin in adulthood.

The major features of dense deposit disease result from kidney malfunction. They most often include a loss of protein in the urine (proteinuria), the presence of blood in the urine (hematuria), reduced amounts of urine, low levels of protein in the blood, and swelling in many areas of the body. The kidney problems associated with this disorder tend to worsen over time, and about half of affected individuals develop end-stage renal disease (ESRD) within 10 years after symptoms appear. ESRD is a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively.

Dense deposit disease can also be associated with other conditions unrelated to kidney function. For example, the disorder can occur with acquired partial lipodystrophy, a condition characterized by a lack of fatty (adipose) tissue under the skin in the upper part of the body. Additionally, some people with dense deposit disease develop a buildup of yellowish deposits called drusen in the light-sensitive tissue at the back of the eye (the retina). These deposits usually appear in childhood or adolescence and can cause vision problems later in life.

Dense deposit disease was previously known as membranoproliferative glomerulonephritis type II (MPGN II). However, recent insights into the underlying cause of the disorder suggest that it is unlikely to be a true form of membranoproliferative glomerulonephritis. Nevertheless, many resources still use the term MPGN II to refer to dense deposit disease.

Dense deposit disease is very rare, affecting 2 to 3 per million people worldwide.

Dense deposit disease is associated with changes in several genes. Mutations that can cause the condition have been identified in the C3 and CFH genes, although these mutations account for only a small percentage of all cases. Several normal variants (polymorphisms) in the C3, CFH, and CFHR5 genes are associated with an increased likelihood of developing dense deposit disease. However, most people with these polymorphisms do not develop the condition.

The genes associated with dense deposit disease provide instructions for making proteins involved in a part of the body's immune response known as the complement system. This system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. The complement system must be carefully regulated so it targets only unwanted materials and does not attack the body's healthy cells.

The gene mutations that cause dense deposit disease lead to uncontrolled activation of the complement system. The overactive system creates debris that builds up in and damages certain structures in the kidneys. These structures, called glomeruli, are clusters of tiny blood vessels that help filter waste products from the blood. Damage to glomeruli prevents the kidneys from filtering waste products normally and can lead to ESRD. Studies suggest that uncontrolled activation of the complement system also causes the other conditions that can occur with dense deposit disease, including acquired partial lipodystrophy and a buildup of drusen in the retina. Researchers are working to determine how these conditions are related to abnormalities of the complement system.

Although dense deposit disease is related to abnormal activation of the complement system, most affected individuals do not have causative mutations in the C3, CFH, or CFHR5 genes. The condition may develop as a result of both genetic risk factors and environmental triggers, most of which are unknown. The disorder can also result from the presence of specific proteins called autoantibodies that block the activity of proteins that regulate the complement system.

Read more about the C3, CFH, and CFHR5 genes.

Most cases of dense deposit disease are sporadic, which means they occur in people with no history of the disorder in their family. Only a few reported families have had more than one family member with the condition. However, several people with dense deposit disease have had close relatives with autoimmune disorders such as celiac disease and type 1 diabetes mellitus. Autoimmune diseases occur when the immune system malfunctions and attacks the body's tissues and organs.