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]

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]

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]

An inherited susceptibility or predisposition to developing acquired partial lipodystrophy. [from MONDO]

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]

Autoimmune lymphoproliferative syndrome type III is an autosomal recessive disorder of immune dysregulation. The phenotype is variable, but most patients have significant lymphadenopathy associated with variable autoimmune manifestations. Some patients may have recurrent infections. Lymphocyte accumulation results from a combination of impaired apoptosis and excessive proliferation (summary by Oliveira, 2013). For a general description and a discussion of genetic heterogeneity of ALPS, see 601859. [from OMIM]

About a third of people with SLE develop kidney disease (nephritis). Heart problems may also occur in SLE, including inflammation of the sac-like membrane around the heart (pericarditis) and abnormalities of the heart valves, which control blood flow in the heart. Heart disease caused by fatty buildup in the blood vessels (atherosclerosis), which is very common in the general population, is even more common in people with SLE. The inflammation characteristic of SLE can also damage the nervous system, and may result in abnormal sensation and weakness in the limbs (peripheral neuropathy); seizures; stroke; and difficulty processing, learning, and remembering information (cognitive impairment). Anxiety and depression are also common in SLE.

People with SLE have episodes in which the condition gets worse (exacerbations) and other times when it gets better (remissions). Overall, SLE gradually gets worse over time, and damage to the major organs of the body can be life-threatening.

SLE may first appear as extreme tiredness (fatigue), a vague feeling of discomfort or illness (malaise), fever, loss of appetite, and weight loss. Most affected individuals also have joint pain, typically affecting the same joints on both sides of the body, and muscle pain and weakness. Skin problems are common in SLE. A characteristic feature is a flat red rash across the cheeks and bridge of the nose, called a "butterfly rash" because of its shape. The rash, which generally does not hurt or itch, often appears or becomes more pronounced when exposed to sunlight. Other skin problems that may occur in SLE include calcium deposits under the skin (calcinosis), damaged blood vessels (vasculitis) in the skin, and tiny red spots called petechiae. Petechiae are caused by a shortage of cells involved in clotting (platelets), which leads to bleeding under the skin. Affected individuals may also have hair loss (alopecia) and open sores (ulcerations) in the moist lining (mucosae) of the mouth, nose, or, less commonly, the genitals.

Systemic lupus erythematosus (SLE) is a chronic disease that causes inflammation in connective tissues, such as cartilage and the lining of blood vessels, which provide strength and flexibility to structures throughout the body. The signs and symptoms of SLE vary among affected individuals, and can involve many organs and systems, including the skin, joints, kidneys, lungs, central nervous system, and blood-forming (hematopoietic) system. SLE is one of a large group of conditions called autoimmune disorders that occur when the immune system attacks the body's own tissues and organs. [from MedlinePlus Genetics]

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]

Systemic lupus erythematosus-17 (SLEB17) is an X-linked dominant autoimmune disorder characterized by onset of systemic autoinflammatory symptoms in the first decades of life. Only affected females have been reported. Features may include classic features of SLE, such as malar rash and arthralgias, or can include less common entities such as hemiplegia and neuromyelitis optica (NMO). Laboratory studies show the presence of autoantibodies and enhanced NFKB (164011) signaling, the latter being consistent with a gain-of-function effect (Brown et al., 2022). For a phenotypic description and a discussion of genetic heterogeneity of systemic lupus erythematosus (SLE), see 152700. [from OMIM]

Immune dysregulation, autoimmunity, and autoinflammation (IDAA) is an immunologic disorder characterized by anemia and thrombocytopenia associated with circulating autoantibodies, positive Coombs test, and increased levels of proinflammatory cytokines due to constitutive activation of immune-related signaling pathways (Tao et al., 2023). [from OMIM]

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