From OMIMComplement factor H deficiency (CFHD) has a variable phenotype. Some patients present with recurrent infections, including increased susceptibility to meningococcal infections, whereas others develop renal disease manifest primarily as C3 glomerulopathy. Affected individuals usually present in the first decades of life with nonspecific findings such as hematuria and may progress to chronic renal failure. As complement factor H is the key regulator of the alternative pathway of the complement system, CFH deficiency results in inappropriate activation of the alternative complement pathway. Laboratory features usually include decreased serum levels of factor H, due to the genetic defect, as well as secondarily decreased levels of complement component C3 (120700) and other alternative pathway components, consistent with consumption of these factors. The renal phenotype is now considered to be a form of C3 glomerulopathy (C3G), which is a pathologic entity in which C3 is deposited within the kidney glomerulus in the mesangial or intramembranous space; this occurs in the absence of immune complexes or immunoglobulins. Terms used to describe this disease include membranoproliferative glomerulonephritis type II (MPGN II), mesangial glomerulonephritis, dense deposit disease (DDD), and C3 glomerulonephritis (summary by Ault, 2000, reviews by Riedl et al., 2017 and Wong and Kavanagh, 2018).
Nomenclature and Classification
Several reviews (Ito et al., 2017, Riedl et al., 2017, Wong and Kavanagh, 2018) have noted that the definition and classification of C3G continues to evolve. Historically, C3G has been referred to as type II membranoproliferative glomerulonephritis (MPGN) or dense deposit disease (DDD) with mesangial or intramembranous deposition of electron dense material. In contrast, MPGN types I and III, which are usually associated with immune complex deposition, tend to show subendothelial and subepithelial electron dense deposits. However, there is significant variability, and the differentiation and distinction between these terms is often unclear. Welch (2002) also discussed the role of complement in renal disease.
A subgroup of patients with MGPN II who do not have mutations in the CFH gene are positive for serum C3 nephritic factor (C3NeF), which is an autoantibody directed against C3bBb, the convertase of the alternative pathway of the complement cascade. Presence of C3NeF prolongs the half-life of C3 convertase, which also results in inappropriate activation of the complement cascade (summary by Abrera-Abeleda et al., 2006).
Genetic Heterogeneity of C3G
C3G2 (610984) is caused by mutation in the CFI gene (217030) on chromosome 4q25, and C3G3 (614809) is caused by mutation in the CFHR5 gene (608593) on chromosome 1q31.
http://www.omim.org/entry/609814 From MedlinePlus GeneticsResearchers have identified two major forms of C3 glomerulopathy: dense deposit disease and C3 glomerulonephritis. Although the two disorders cause similar kidney problems, the features of dense deposit disease tend to appear earlier than those of C3 glomerulonephritis, usually in adolescence. However, the signs and symptoms of either disease may not begin until adulthood.
The kidney problems associated with C3 glomerulopathy tend to worsen over time. About half of affected individuals develop end-stage renal disease (ESRD) within 10 years after their diagnosis. ESRD is a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively.
One of the two forms of C3 glomerulopathy, dense deposit disease, can also be associated with other conditions unrelated to kidney function. For example, people with dense deposit disease may have 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.
C3 glomerulopathy is a group of related conditions that cause the kidneys to malfunction. The major features of C3 glomerulopathy include high levels of protein in the urine (proteinuria), blood in the urine (hematuria), reduced amounts of urine, low levels of protein in the blood, and swelling in many areas of the body. Affected individuals may have particularly low levels of a protein called complement component 3 (or C3) in the blood.
https://medlineplus.gov/genetics/condition/c3-glomerulopathy