Rare Ophthalmology News

Disease Profile

Dense deposit disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Childhood

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ICD-10

N03.6

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Glomerulonephritis membranoproliferative type 2; Mesangiocapillary glomerulonephritis type 2; MPGN 2;

Categories

Congenital and Genetic Diseases; Kidney and Urinary Diseases

Summary

Dense deposit disease (DDD) is a condition that primarily affects kidney function. Signs and symptoms usually start between the ages of 5 and 15 but may also begin in adulthood. The major features of DDD are due to kidney malfunction, and often include proteinuria; hematuria; reduced amounts of urine; low levels of protein in the blood; and swelling in many areas of the body. About half of affected people develop end-stage renal disease (ESRD) within 10 years after symptoms start. DDD can have genetic or non-genetic causes. It can be caused by mutations in the C3 and CFH genes; it may develop as a result of both genetic risk factors and environmental triggers; or it can result from the presence of autoantibodies that block the activity of proteins needed for the body's immune response. Most cases are sporadic (occurring by chance in people with no history of the disorder in their family).[1]

Symptoms

The major features of dense deposit disease (DDD) result from kidney malfunction. They usually include increased 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 DDD tend to worsen over time, and about half of affected people develop end-stage renal disease (ESRD) within 10 years after symptoms start.[1]

Some people with DDD develop a buildup of yellowish deposits called drusen in the retina of the eye. These deposits usually appear in childhood or adolescence and can cause vision problems later in life.[1] The long-term risk of vision problems in people with DDD is about 10% (1 in 10).[2]

DDD can sometimes be associated with other conditions that are not related to kidney function. For example, it can occur with acquired partial lipodystrophy (APL), a condition characterized by a lack of fatty tissue under the skin of the upper body.[1] In people with APL, the loss of fat in the upper body usually occurs several years before kidney disease starts.[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Autosomal recessive inheritance
0000007
Chronic kidney disease
0012622
Decreased serum complement factor H
0005369
Depletion of components of the alternative complement pathway
0005389
Glomerular subendothelial electron-dense deposits
0004746
Hematuria
Blood in urine
0000790
Juvenile onset
Signs and symptoms begin before 15 years of age
0003621
Recurrent bacterial infections
Bacterial infections, recurrent
Frequent bacterial infections
Increased susceptibility to bacterial infections
Recurrent major bacterial infections

[ more ]

0002718
Thickened glomerular basement membrane
0004722

Cause

Dense deposit disease (DDD) can have genetic or non-genetic causes. When the condition is genetic, it may be associated with changes in several genes. Mutations that cause the condition have been identified in the C3 and CFH genes, but they account for only a small percentage of all cases. There are also variants of some genes (C3, CFH and CFHR5) that do not directly cause the condition, but increase the likelihood of developing the condition. Most people with these variants do not develop the condition.[3]

Most people with DDD do not have disease-causing mutations in the C3, CFH, or CFHR5 genes. The condition may develop due to a combination of genetic and environmental risk factors ("triggers"), most of which are unknown. The condition can also be caused by the presence of specific proteins called autoantibodies that block the activity of proteins needed for the body's immune response.[3]

Treatment

There is currently no specific treatment for dense deposit disease (DDD), but therapies are available to help slow the progression of the condition through aggressive blood pressure control and reduction of proteinuria. Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type-1 receptor blockers (ARBs) can be used to decrease the amount of protein in the urine and improve kidney function. These drugs may also limit the infiltration of white blood cells into the kidney. If hyperlipidemia (increased lipid in the blood stream) is present, lipid-lowering drugs may be used to reduce long-term risks of atherosclerosis. These drugs may also delay progression of kidney disease. Steroid therapy was widely used in the past, but more recent studies have shown that it is probably not effective for DDD. Steroid therapy is effective in a form of glomerulonephritis called juvenile acute non-proliferative glomerulonephritis (JANG), which is sometimes confused with DDD.[5]

People with DDD who develop end-stage renal disease typically need peritoneal dialysis or hemodialysis. Kidney transplant may be an option for some individuals; however, DDD will still develop in virtually all transplanted kidneys and about half of transplants will ultimately fail. There is some evidence that the likelihood of transplant failure due to recurrent DDD decreases with time.[5]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Dense deposit disease. Click on the link to view a sample search on this topic.

          References

          1. Dense deposit disease. Genetics Home Reference. February 2011; https://ghr.nlm.nih.gov/condition/dense-deposit-disease. Accessed 12/12/2014.
          2. Corchado JC, Smith RJH. Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II. GeneReviews. May 19, 2011; https://www.ncbi.nlm.nih.gov/books/NBK1425/. Accessed 12/12/2014.
          3. Dense Deposit Disease. Genetics Home Reference. February, 2011; https://ghr.nlm.nih.gov/condition/dense-deposit-disease. Accessed 2/24/2014.
          4. Johnny Cruz Corchado and Richard JH Smith. Dense Deposit Disease/Membranoproliferative Glomerulonephritis Type II. GeneReviews. May 19, 2011; https://www.ncbi.nlm.nih.gov/books/NBK1425/. Accessed 2/24/2014.
          5. Dense Deposit Disease. NORD. July 28, 2010; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1149/viewAbstract. Accessed 4/20/2012.

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