Immunodeficiency, and Hepatitis

HCV, which is principally transmitted by blood, infects about 3% of the world's population. HCV infection causes acute hepatitis, which is self-resolving in 20 to 50% of cases but does not confer permanent immunity. In 50 to 80% of cases, HCV infection becomes chronic and results in chronic hepatitis, cirrhosis, and hepatocellular carcinoma. As a result, HCV infection is a leading killer worldwide and the most common cause of liver failure in the U.S. HCV is opportunistic in individuals infected with human immunodeficiency virus (HIV; see {609423}), approximately 25% of whom are coinfected with HCV. HCV infection is also associated with cryoglobulinemia (see {123550}), a B-lymphocyte proliferative disorder (Pawlotsky, 2004; Chisari (2005); Pileri et al., 1998).

HEPATITIS C VIRUS, SUSCEPTIBILITY TO Is also known as hcv, susceptibility to

• Immunodeficiency
• Carcinoma
• Cirrhosis
• Hepatic failure
• Hepatitis

SOURCES: OMIM MENDELIAN

Immunodeficiency-56 is an autosomal recessive primary immunodeficiency characterized by B- and T-cell defects and variable dysfunction of NK cells. Patients tend to have normal numbers of lymphocytes, but show defective class-switched B cells, low IgG, defective antibody response, and defective T-cell responses to certain antigens (summary by Kotlarz et al., 2013).

COMBINED IMMUNODEFICIENCY DUE TO IL21R DEFICIENCY Is also known as il21r immunodeficiency

• Failure to thrive
• Immunodeficiency
• Recurrent infections
• Pneumonia
• Abnormality of the liver

SOURCES: OMIM ORPHANET MENDELIAN

Immunodeficiency-19 (IMD19) is an autosomal recessive form of severe combined immunodeficiency (SCID) characterized by onset in early infancy of recurrent bacterial, viral, and fungal infections. Patients usually have chronic diarrhea, recurrent respiratory infections, and failure to thrive. Immunologic work-up shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype. The disorder is lethal in early childhood without bone marrow transplantation (summary by Yu et al., 2011).

IMMUNODEFICIENCY 19; IMD19 Is also known as scid, t cell-negative, b cell-positive, nk cell-positive|cd3-delta deficiency|severe combined immunodeficiency, t cell-negative, b cell-positive, nk cell-positive

• Failure to thrive
• Fever
• Respiratory distress
• Diarrhea
• Immunodeficiency

SOURCES: OMIM MENDELIAN

Trichohepatoenteric syndrome (THES) is a rare and severe disease characterized by intrauterine growth retardation, facial dysmorphism, hair abnormalities, intractable diarrhea, and immunodeficiency (summary by Fabre et al., 2012).For a discussion of genetic heterogeneity of trichohepatoenteric syndrome, see THES1 (OMIM ).

• Growth delay
• Hypertelorism
• Failure to thrive
• Abnormal facial shape
• Anemia

SOURCES: OMIM MENDELIAN

IL21-RELATED INFANTILE INFLAMMATORY BOWEL DISEASE Is also known as il21-related infantile ibd|il21 deficiency

• Growth delay
• Failure to thrive
• Diarrhea
• Immunodeficiency
• Recurrent respiratory infections

SOURCES: OMIM ORPHANET MENDELIAN

AGAMMAGLOBULINEMIA 4, AUTOSOMAL RECESSIVE; AGM4 Is also known as agammaglobulinemia, autosomal recessive, due to blnk defect

• Diarrhea
• Immunodeficiency
• Pneumonia
• Neutropenia
• Sepsis

SOURCES: OMIM MENDELIAN

Immunodeficiency by defective expression of HLA class 2 is a rare primary genetic immunodeficiency disorder characterized by partial or complete absence of human leukocyte antigen class 2 expression resulting in severe defect in both cellular and humoral immune response to antigens. The disorder presents clinically as marked susceptibility to infections, severe malabsorption and failure to thrive and is often fatal in early childhood.

IMMUNODEFICIENCY BY DEFECTIVE EXPRESSION OF HLA CLASS 2 Is also known as bls|major histocompatibility complex class ii expression deficiency|bare lymphocyte syndrome type 2|bls, type ii|hla class 2-negative severe combined immunodeficiency|bare lymphocyte syndrome|scid, hla class ii-negative|hla class 2-negative scid|mhc class

• Failure to thrive
• Immunodeficiency
• Recurrent infections
• Malabsorption
• Neutropenia

SOURCES: OMIM ORPHANET MESH MENDELIAN

Immunodeficiency due to a classical component pathway complement deficiency is a primary immunodeficiency due to a deficiency in either complement components C1q, C1r, C1s, C2 or C4 characterized by increased susceptibility to bacterial infections, particularly with encapsulated bacteria, and increased risk for autoimmune disease. Most commonly, these include systemic lupus erythematosus (SLE), SLE-like disease, Henoch-Schonlein purpura, polymyositis and arthralgia. Disease severity is variable and dependent on the complement affected.

IMMUNODEFICIENCY DUE TO A CLASSICAL COMPONENT PATHWAY COMPLEMENT DEFICIENCY Is also known as immunodeficiency due to c1, c4, or c2 component complement deficiency|immunodeficiency due to an early component of complement deficiency

• Pain
• Cataract
• Fever
• Renal insufficiency
• Immunodeficiency

SOURCES: OMIM ORPHANET MENDELIAN

XLP2 is an X-linked primary immune deficiency with symptom onset usually in the first years of life, although later onset may occur. Features are compatible with immune dysregulation and include hemophagocytic lymphohistiocytosis (HLH), often associated with chronic Epstein-Barr virus (EBV) infection, splenomegaly, fever, colitis or inflammatory bowel disease (IBD), and recurrent infections. Laboratory abnormalities are variable, but can include hypogammaglobulinemia, cytopenias, and low levels of a particular subset of T cells known as NKT (or iNKT) cells. Functional studies show increased sensitivity of T cells to apoptosis (activation-induced cell death, AICD), impaired cytokine production, including of TNF-alpha (TNFA ), and general dysregulation of the immune pathway, such as increased levels of IL18 (OMIM ). However, circulating levels of lymphocytes and NK cells are usually normal. Many patients die from fulminant HLH, and the only curative treatment is a hematopoietic stem cell transplant, although this procedure has been associated with a poor prognosis. Female mutation carriers are usually asymptomatic, although some female carriers may have less severe manifestations, which appears to depend on X-inactivation patterns (summary by Yang et al., 2012; review by Latour and Aguilar, 2015).Latour and Aguilar (2015) provided a detailed review of XIAP deficiency, including clinical features, molecular genetics, and pathophysiology.For a general phenotypic description and a discussion of genetic heterogeneity of X-linked lymphoproliferative syndrome, see XLP1 (OMIM ).

LYMPHOPROLIFERATIVE SYNDROME, X-LINKED, 2; XLP2 Is also known as xiap deficiency

• Anemia
• Fever
• Splenomegaly
• Immunodeficiency
• Recurrent infections

SOURCES: OMIM MENDELIAN

Hemophilia B due to factor IX deficiency is phenotypically indistinguishable from hemophilia A (OMIM ), which results from deficiency of coagulation factor VIII (F8 ). The classic laboratory findings in hemophilia B include a prolonged activated partial thromboplastin time (aPTT) and a normal prothrombin time (PT) (Lefkowitz et al., 1993).Early studies made a distinction between cross-reactive-material (CRM)-negative and CRM-positive hemophilia B mutants. This classification referred to detection of the F9 antigen in plasma, even in the presence of decreased F9 activity. Detection of the antigen indicated the presence of a dysfunctional F9 protein. Roberts et al. (1968) found that about 90% of patients with hemophilia B were CRM-negative, whereas about 10% were CRM-positive. However, Bertina and Veltkamp (1978) found that a rather large proportion of the hemophilia B patients could be characterized as hemophilia B CRM+. They identified 14 cases of hemophilia B CRM+ from 11 families among a group of 33 patients. After immunologic and activity comparisons, they found at least 7 different factor IX variants. Bertina and Veltkamp (1978) noted the high heterogeneity within this group. In an editorial on variants of vitamin K-dependent coagulation factors, Bertina et al. (1979) stated that 9 defective variants of factor II, 5 variants of factor X, and many variants (about 180 pedigrees) of factor IX had been identified. At least one variant of factor VII (Padua) was also known.

HEMOPHILIA B; HEMB Is also known as christmas disease|factor ix deficiency|f9 deficiency|plasma thromboplastin component deficiency

• Immunodeficiency
• Leukemia
• Hematuria
• Abnormal bleeding
• Gastrointestinal hemorrhage

SOURCES: OMIM ORPHANET MENDELIAN