MedGen

Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. The onset of atypical HUS (aHUS) ranges from the neonatal period to adulthood. Genetic aHUS accounts for an estimated 60% of all aHUS. Individuals with genetic aHUS frequently experience relapse even after complete recovery following the presenting episode; 60% of genetic aHUS progresses to end-stage renal disease (ESRD). [from GeneReviews]

Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. The onset of atypical HUS (aHUS) ranges from the neonatal period to adulthood. Genetic aHUS accounts for an estimated 60% of all aHUS. Individuals with genetic aHUS frequently experience relapse even after complete recovery following the presenting episode; 60% of genetic aHUS progresses to end-stage renal disease (ESRD). [from GeneReviews]

C3 glomerulopathy (C3G) is a complex ultra-rare complement-mediated renal disease caused by uncontrolled activation of the complement alternative pathway (AP) in the fluid phase (as opposed to cell surface) that is rarely inherited in a simple mendelian fashion. C3G affects individuals of all ages, with a median age at diagnosis of 23 years. Individuals with C3G typically present with hematuria, proteinuria, hematuria and proteinuria, acute nephritic syndrome or nephrotic syndrome, and low levels of the complement component C3. Spontaneous remission of C3G is uncommon, and about half of affected individuals develop end-stage renal disease (ESRD) within ten years of diagnosis, occasionally developing the late comorbidity of impaired visual acuity. [from GeneReviews]

C3 glomerulopathy (C3G) is a complex ultra-rare complement-mediated renal disease caused by uncontrolled activation of the complement alternative pathway (AP) in the fluid phase (as opposed to cell surface) that is rarely inherited in a simple mendelian fashion. C3G affects individuals of all ages, with a median age at diagnosis of 23 years. Individuals with C3G typically present with hematuria, proteinuria, hematuria and proteinuria, acute nephritic syndrome or nephrotic syndrome, and low levels of the complement component C3. Spontaneous remission of C3G is uncommon, and about half of affected individuals develop end-stage renal disease (ESRD) within ten years of diagnosis, occasionally developing the late comorbidity of impaired visual acuity. [from GeneReviews]

Age-related macular degeneration-4 (ARMD) is a disorder of the eye characterized by the formation of drusen on the retina, often as cuticular drusen which appear in a 'starry sky' distribution on fluorescein angiography. The disorder results in a progressive loss of central vision (summary by Hageman et al., 2005, Grassi et al., 2007). [from OMIM]

The presence of autoantibodies (immunoglobulins) in the serum that react against C3 convertase (C3bBb). [from HPO]

MDDGC3 is a rare form of autosomal recessive limb-girdle muscular dystrophy with normal cognition (Clement et al., 2008). It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Godfrey et al., 2007). For a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type C, see MDDGC1 (609308). [from OMIM]

Age-related macular degeneration (ARMD) is a progressive degeneration of photoreceptors and underlying retinal pigment epithelium (RPE) cells in the macula region of the retina. It is a highly prevalent disease and a major cause of blindness in the Western world. Drusen, pale excrescences of variable size, and other deposits accumulate below the RPE on the Bruch membrane; clinical and histopathologic investigations have shown that these extracellular deposits are the hallmark of early ARMD. As ARMD advances, areas of geographic atrophy of the RPE can cause visual loss, or choroidal neovascularization can occur to cause wet, or exudative, ARMD with accompanying central visual loss (summary by De et al., 2007). Genetic Heterogeneity of Age-Related Macular Degeneration ARMD2 (153800) is associated with mutation in the ABCR gene (601691) on chromosome 1p, and ARMD3 (608895) is caused by mutation in the FBLN5 gene (604580) on chromosome 14q31. Up to 50% of the attributable risk of age-related macular degeneration (ARMD4; 610698) appears to be explained by a polymorphism in the CFH gene (134370.0008). ARMD5 (613761) and ARMD6 (613757) are associated with mutation in the ERCC6 (609413) and RAX2 (610362) genes, respectively. ARMD7 (610149) and ARMD8 (613778), which both represent susceptibility linked to chromosome 10q26, are associated with single-nucleotide polymorphisms in the HTRA1 (602194) and ARMS2 (611313) genes, respectively. ARMD9 (611378) is associated with single-nucleotide polymorphisms in the C3 gene (120700). ARMD10 (611488) maps to chromosome 9q32 and may be associated with a polymorphism in the TLR4 gene (603030). ARMD11 (611953) is association with variation in the CST3 gene (604312); ARMD12 (613784) with variation in the CX3CR1 gene (601470); and ARMD13 (615439) with variation in the CFI gene (217030). ARMD14 (615489) is associated with variation in or near the C2 (613927) and CFB (138470) genes on chromosome 6p21. ARMD15 (615591) is associated with variation in the C9 gene (120940). There is evidence for a form of ARMD caused by mutation in the mitochondrial gene MTTL1 (590050). A haplotype carrying deletion of the complement factor H-related genes CFHR1 (134371) and CFHR3 (605336) is also associated with reduced risk of ARMD. Lotery and Trump (2007) reviewed the molecular biology of age-related macular degeneration and tabulated the genes associated with ARMD, including those with only positive findings versus genes for which conflicting results have been found. [from OMIM]

In 10 to 15 percent of affected individuals, the dry form progresses to the wet form of age-related macular degeneration. The wet form is characterized by the growth of abnormal, fragile blood vessels underneath the macula. These vessels leak blood and fluid, which damages the macula and makes central vision appear blurry and distorted. The wet form of age-related macular degeneration is associated with severe vision loss that can worsen rapidly.

Researchers have described two major types of age-related macular degeneration, known as the dry form and the wet form. The dry form is much more common, accounting for 85 to 90 percent of all cases of age-related macular degeneration. It is characterized by a buildup of yellowish deposits called drusen beneath the retina and vision loss that worsens slowly over time. The most advanced stage of dry age-related macular degeneration is known as geographic atrophy, in which areas of the macula waste away (atrophy), resulting in severe vision loss. Dry age-related macular degeneration typically affects vision in both eyes, although vision loss often occurs in one eye before the other.

Age-related macular degeneration mainly affects central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. The vision loss in this condition results from a gradual deterioration of light-sensing cells in the tissue at the back of the eye that detects light and color (the retina). Specifically, age-related macular degeneration affects a small area near the center of the retina, called the macula, which is responsible for central vision. Side (peripheral) vision and night vision are generally not affected, but slow adjustment of vision to darkness (dark adaptation) and reduced dim light (scotopic) vision often occur in the early stages of the disease.

Age-related macular degeneration is an eye disease that is a leading cause of vision loss in older people in developed countries. Subtle abnormalities indicating changes in vision may occur in a person's forties or fifties. Distorted vision and vision loss usually become noticeable in a person's sixties or seventies and tend to worsen over time. [from MedlinePlus Genetics]

The presence of complement 3 deposits in the glomerulus. [from HPO]

Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch membrane. They appear as slightly raised, yellow subretinal nodules randomly scattered in the macula. 'Drusen' is the plural for 'Druse,' German for 'nodule' or 'crystal' (summary by Bok, 2002, Boon et al., 2008). [from OMIM]

Concentration of the complement component C3 in the blood circulation below the lower limit of normal. [from HPO]

C3 glomerulopathy (C3G) is a complex ultra-rare complement-mediated renal disease caused by uncontrolled activation of the complement alternative pathway (AP) in the fluid phase (as opposed to cell surface) that is rarely inherited in a simple mendelian fashion. C3G affects individuals of all ages, with a median age at diagnosis of 23 years. Individuals with C3G typically present with hematuria, proteinuria, hematuria and proteinuria, acute nephritic syndrome or nephrotic syndrome, and low levels of the complement component C3. Spontaneous remission of C3G is uncommon, and about half of affected individuals develop end-stage renal disease (ESRD) within ten years of diagnosis, occasionally developing the late comorbidity of impaired visual acuity. [from GeneReviews]

C3 glomerulopathy-3 (C3G3) is an autosomal dominant kidney disease characterized by the onset of microscopic or macroscopic hematuria in the first 3 decades of life, followed by variable progression of renal disease. After age 30, about half of patients continue to have episodic hematuria while maintaining normal renal function, whereas the other half develop proteinuria and progressive renal failure or end-stage renal disease. In some cases, renal dysfunction may be triggered or exacerbated by an infectious disease, often an upper respiratory infection or pharyngitis. Some patients may also develop hypertension. Renal biopsy shows glomerular C3 deposition and mesangial proliferation with glomerulonephritis. Membranoproliferative glomerulonephritis (MPGN) may also be observed on renal biopsy. Males tend to have a more severe phenotype than females and are more likely to develop end-stage renal disease, often necessitating dialysis or renal transplant (summary by Athanasiou et al., 2011). For a general description and discussion of genetic heterogeneity of C3G, see C3G1 (609814). [from OMIM]

Acquired partial lipodystrophy (APLD) is characterized clinically by the gradual onset of bilaterally symmetrical loss of subcutaneous fat from the face, neck, upper extremities, thorax, and abdomen, in the 'cephalocaudal' sequence, sparing the lower extremities. A large group of patients (83%) with acquired partial lipodystrophy have low serum levels of complement component C3 due to the presence of C3 nephritic factor, an IgG antibody that causes continuous activation of the alternative complement pathway and consumption of serum C3. About 22% of patients with this acquired complement defect develop membranoproliferative glomerulonephritis. Some individuals may also show an increased risk of infection (Misra et al., 2004). Acquired partial lipodystrophy is not inherited in a classic mendelian pattern; it rather represents a phenotype with a complex etiology. Affected individuals may have genetic susceptibility factors that require the additional presence of environmental factors or acquired disorders to be expressed (summary by Hegele et al., 2006). Most cases are sporadic, family history is negative, and females are more often affected than males (ratio, 4:1) (summary by Misra et al., 2004). See 608709 for a subtype of APLD not associated with low complement C3 or renal disease. [from OMIM]

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.

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.

Researchers 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.

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. [from MedlinePlus Genetics]

A rare genetic primary immunodeficiency with characteristics of susceptibility to infection (mainly by gram negative bacteria) due to extremely low C3 plasma levels. Patients typically present recurrent episodes of sinusitis, tonsillitis, and/or otitis, as well as upper and lower respiratory tract infections (including pneumonia) and skin infections, such as erythema multiforme. Autoimmune disease resembling systemic lupus erythematosus and mesangiocapillary or membranoproliferative glomerulonephritis may develop, resulting in renal failure. The disease is caused by homozygous or compound heterozygous mutation in the C3 gene on chromosome 19p13. [from SNOMEDCT_US]

C3 glomerulopathy (C3G) is a complex ultra-rare complement-mediated renal disease caused by uncontrolled activation of the complement alternative pathway (AP) in the fluid phase (as opposed to cell surface) that is rarely inherited in a simple mendelian fashion. C3G affects individuals of all ages, with a median age at diagnosis of 23 years. Individuals with C3G typically present with hematuria, proteinuria, hematuria and proteinuria, acute nephritic syndrome or nephrotic syndrome, and low levels of the complement component C3. Spontaneous remission of C3G is uncommon, and about half of affected individuals develop end-stage renal disease (ESRD) within ten years of diagnosis, occasionally developing the late comorbidity of impaired visual acuity. [from GeneReviews]

An abnormal reduction in the components of the alternative complement pathway, such as the C3 protein or its cleavage products. [from HPO]

Presence of complement C3 in the dermoepidermal junction that are distributed in a linear pattern. This feature can be appreciated by immunofluorescence microscopy. [from HPO]