It is the most common form of hyperigm syndrome, accounting for approximately 70% of cases. Hyper igm syndrome is an xlinked genetic disorder more commonly affecting males than females. Hyperigm syndrome is an immunoglobulin ig deficiency characterized by normal or elevated serum igm levels and decreased levels or absence of other serum immunoglobulins, resulting in susceptibility to bacterial infections. The child is now on regular immunoglobulin therapy and is free from recurrent infections. Hyper igm syndrome type 5 characterized by mutations of the ung gene. Hyperigm syndrome definition of hyperigm syndrome by. Diagnosis of hyper igm syndrome is suspected based on clinical criteria, including recurrent sinopulmonary infections, chronic diarrhea, and lymphoid hyperplasia. In terms of treatment for hyper igm syndrome, there is the use of allogeneic hematopoietic cell transplantation.
Hyper igm syndromes are a group of rare disorders in which the immune system does. Higm syndrome manifests as a t cell dysfunction rather than a b cell dysfunction, despite hypogammaglobulinemia, because most cases are caused by a mutation of the cd40l gene located at the x chromosome. Hyperigm syndrome type 4 with a b lymphocyteintrinsic selective deficiency in ig classswitch recombination article pdf available in journal of clinical investigation 1121. Immunodeficiency with hyperigm was described by israelasselain et al. In boys, failure to express cd40 ligand on tcells can be demonstrated. Xlinked hyper igm syndrome genetics home reference nih. In this type, b cells cannot recombine genetic material to change heavy chain production, which is a required step in switching classes.
Immunodeficiency with hyper igm was described by israelasselain et al. Hyper igm syndromes are caused by very rare, oneinamillion, and potentially lifethreatening genetic mutations that severely compromise the immune system and resulting in the individuals inability to produce antibodies. Hyper igm syndrome prof ariyanto harsono md phd spak 2. Hyper igm syndrome how is hyper igm syndrome abbreviated. Immunodeficiency diseases study guide by lrpence includes 58 questions covering vocabulary, terms and more. These three patients instead had mutations in the catalytic domain of uracildna glycosylase, an enzyme that removes uracil from dna.
Kepvords immunodeficiency disorder, hyper igm syndrome, irnmunoglobulin. Although there are several treatments that can help maintain a generally healthy status quo, the comorbidity and general outcomes vary within the patient population. Hyper igm syndrome is a primary immunodeficiency pid which should be managed and followed closely by an immunologist with experience treating pids. Genetic heterogeneity of immunodeficiency with hyper igm other forms of higm include higm2 605258, which results from mutation in the aicda gene 605257, higm3 606843, which results from mutation in the cd40 gene 109535, and higm5 608106, which results from mutation in the ung gene 191525.
For a discussion of genetic heterogeneity of immunodeficiency with. Immunodeficiency with hyper igm type 1 genetic and rare. The most common form is inherited as an xchromosome linked trait and affects only boys. Most of the other forms are inherited as autosomal recessive traits and affect both girls and boys.
Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. Genetic tests to detect specific mutations can be done in specialized laboratories. Neutropenia may be accompanied by gingivitis, ulcerative stomatitis, fever, and weight loss levy et al. In this type, b cells cannot receive the signal from t cells to switch classes. The hyper igm syndromes are a group of rare inherited immune deficiency. This condition may be characterized by recurrent pusproducing pyogenic bacterial infections of the upper and lower respiratory tract including the sinuses sinusitis andor the lungs pneumonitis or pneumonia.
In both type 2 and type 5 hyperigm syndromes, the patients are profoundly. The affected individuals are virtually always male, because males only have one x chromosome, received from their mothers. They are found in blood and lymph fluid and are the first type of antibody made in response to an infection. When the cd40 ligand binds cd40 on b cells, then the b cell switches from producing igm to producing iga or igg. Hyperigm syndrome, which is characterized by the presence of normal or elevated serum levels of igm and low igg and iga, may be caused by one of at least 10 gene defects table 17.
Any one with igm nephrotic syndrome nephrotic syndrome. Immunodeficiency with hyper igm is a rare genetic disorder characterized by recurrent infections in association with markedly decreased serum igg, iga, and ige levels but normal or elevated. Clinical spectrum of xlinked hyperigm syndrome sciencedirect. Abstract elevated ige levels can be associated with a variety of causes. Hyper igm syndrome, which is characterized by the presence of normal or elevated serum levels of igm and low igg and iga, may be caused by one of at least 10 gene defects table 17. Jun 25, 20 the hyper igm syndromes are a group of rare inherited immune deficiency disorders characterized by impairment of immunoglobulin isotype switching resulting from defects in the cd40 ligandcd40 signaling pathway. Hyper igm syndrome switch or not to switch request pdf. Hyper igm syndrome type 4 which is a defect in class switch recombination downstream of the aicda gene that does not impair somatic hypermutation. The symptoms are similar to hyper igm syndrome type 2, but the aicda gene is intact. Immunodeficiency with hyperigm is a rare genetic disorder characterized by recurrent infections in association with markedly decreased serum igg, iga, and ige levels but normal or elevated.
The most common and the most clinically severe of these is an xlinked deficiency in cd40 ligand cd40 l. In addition, cd40 ligand is important for other tlymphocyte functions, and therefore, patients with xlinked hyper igm syndrome xhim also have a defect in some of the protective functions of their tlymphocytes. Immunodeficiency with hyper igm type 3 genetic and rare. Because isotype switching of antibody cannot occur, there is a selective hypogammaglobulinemia of igg, iga, and ige. Hyper igm syndrome type 2 higm2 is a rare immunodeficiency characterized by normal or elevated serum igm levels with absence of igg, iga, and ige, resulting in a profound susceptibility to bacterial infections. When the cd40 ligand binds cd40 on b cells, then the b cell switches from producing igm to producing iga or igg in these patients a biopsy of a lymph node may show poor development of. B essential modulator, while autosomal recessive forms of hyper igm are caused by defects in cd40 or.
Other forms of hyper igm are inherited as autosomal recessive traits and can. World map of hyper igm syndrome find people with hyper igm syndrome through the map. Other forms of hyper igm syndrome are inherited as autosomal recessive traits and have been observed in females and males. Hyperigm syndrome type 2 higm2 is a rare immunodeficiency characterized by normal or elevated serum igm levels with absence of igg, iga, and ige, resulting in a profound susceptibility to bacterial infections. Xlinked hyper igm syndrome is a condition that affects the immune system and occurs almost exclusively in males.
National center for case study teaching in science hyperigm. They also cause other immune system cells to destroy foreign substances. Patients with the hyper igm syndrome have an inability to switch their antibody immunoglobulin production from igm to igg, iga, and ige. Pubmed is a searchable database of medical literature and lists journal articles that discuss immunodeficiency with hyper igm type 3.
Ssprimary sjogrens syndrome, slesystemic lupus erythertiatosus, rarheumatoid arthritis, sssiogrens syndrome, raynaudraynauds phenomenon, pssprogressive systemic sclerosis. The clinical course of xlinked hyperigm syndrome is similar to that of xlinked brutontype agammaglobulinemia except for a greater frequency of autoimmune hematologic disorders neutropenia, hemolytic anemia, thrombocytopenia. As a result, patients with this disease have decreased levels of igg and iga but normal or elevated levels of igm in their blood. Diagnosis of hyperigm syndrome is suspected based on clinical criteria, including recurrent sinopulmonary infections, chronic diarrhea, and lymphoid hyperplasia. My son was diagnosed with igm nephrotic syndrome 2 days after hurricane ike he was 18 months old when he started swellingwe were put in texas childrens hospital where we stayed for on and off for 2 years until he was put on sandimmune. Unlike xlinked hyper igm syndrome or hyper igm syndrome type 3, which affect both the t cell and b cell systems, these two forms of the disorder only affect the b cell system. Xlinked forms of hyper igm are caused by defects in the cd40 ligand gene or nf. Any one with igm nephrotic syndrome nephrotic syndrome and. Immunologic profiling showed decreased b cells in 74. Hyper igm syndromes is a group of primary immune deficiency disorders characterized by defective cd40 signaling. Hyperigm syndrome type 4 which is a defect in class switch recombination downstream of the aicda gene that does not impair somatic hypermutation. Xlinked hyper igm syndrome higm1, a disorder of abnormal t and. Quizlet flashcards, activities and games help you improve your grades. Oct 23, 2019 xlinked immunodeficiency with hyper immunoglobulin m xhigm or higm1 is a rare form of primary immunodeficiency disease caused by mutations in the gene that codes for cd40 ligand cd40l, also known as cd154 and gp39.
The hyper igm syndromes are a group of rare inherited immune deficiency disorders. Pdf mutations in pik3cd can cause hyper igm syndrome higm. Hyper igm syndrome type 2 autosomal recessive characterized by mutations of the aicda gene. The fifth type of hyperigm syndrome has been characterized in three patients from france and japan.
Hyperigm syndrome type 5 characterized by mutations of the ung gene. Hyperigm syndrome by gopalan and kist page 2 the case th ree yearold adam presented with a fever and frequent episodes of coughing. He had a history of recurrent pneumonia and sinus infections since he was six monthsold, but appeared to be of normal physical and mental function. Hyperigm syndrome how is hyperigm syndrome abbreviated. Primary immunodeficiency occurs when part of a persons immune system is missing or does not work correctly. Xlinked hyperigm syndrome omim 308230 is a genetic immunodeficiency syndrome that presents with bacterial and opportunistic infections from an early age. Their mothers are not symptomatic, even though they are carriers of.
Hyper igm syndrome is a type of primary immunodeficiency syndrome. The hyper igm syndromes are a group of rare inherited immune deficiency disorders characterized by impairment of immunoglobulin isotype switching resulting from defects in the cd40 ligandcd40 signaling pathway. Hyper igm syndrome type 5 is inherited in an autosomal recessive manner the fifth type of hyper igm syndrome has been characterized in three patients from france and japan. Hyper igm syndrome is a very rare, oneinamillion, and potentially lifethreatening genetic mutation that severely compromises the immune system. An index of suspicion to consider a possible diagnosis ofimmunodeficiency is stressed. Cd40 ligand is expressed on activated t lymphocytes and is necessary for t cells to induce b cells to undergo immunoglobulin. In this case report we describe a patient with elevated ige levels and our. Hyper igm syndrome medigoo health medical tests information. Mar 10, 20 hyper igm syndrome immunologic phenotype presenting with low igg, iga, and ige levels with normal or increased igm levels the term hyper igm is a misnomer igm levels are not necessarily high the relative excess of igm is due to a defect in class switch recombination csr in certain cases somatic hypermutation shm is also affected uygungil. The predominant immunologic phenotype was hyperigm syndrome 48. There are at least four types of autosomal recessive hyper igm syndrome. Pdf mutations in pik3cd can cause hyper igm syndrome. May 01, 2020 access to this database is free of charge.
Xlinked hyperigm syndrome xhigm is one type of primary. This variant of the hyper igm syndrome is caused by mutation of the cd40lg gene. Aug 17, 2011 my son was diagnosed with igm nephrotic syndrome 2 days after hurricane ike he was 18 months old when he started swellingwe were put in texas childrens hospital where we stayed for on and off for. Both primary and acquired forms of the disease have been reported. Xlinked hyper igm syndrome omim 308230 is a genetic immunodeficiency syndrome that presents with bacterial and opportunistic infections from an early age. Introduction the initial terminology of hyper igm syndrome is really xlinked immunodeficiency with hyper immunoglobulin m xhigm or higm1 is a rare form of primary immunodeficiency disease caused by mutations in the gene that codes for cd40 ligand cd40l, also known as cd154 and gp39.
Click on the link to view a sample search on this topic. Diagnosis of hyper igm syndrome is suspected in patients with low or absent igg or iga and normal or elevated igm antibodies. The hyper igm syndrome higm is one of the rarest primary immunodeficiencies. Hyper igm syndrome type 1 higm1 is the xlinked variant of the hyperigm syndrome. Patients with hyper igm are at significant risk for opportunistic and repeated infections.
Hyper igm syndrome is an immunoglobulin ig deficiency characterized by normal or elevated serum igm levels and decreased levels or absence of other serum immunoglobulins, resulting in susceptibility to bacterial infections. Hyperigm syndrome type 3 characterized by mutations of the cd40 gene. Aazathioprine, chchloroquine phosphate, cycyclophosphamide, pprednisolone. This gene codes for the cd40 ligand, which is expressed on t cells. Pdf hyperigm syndrome a case report and a clinical. Hyper igm syndromes nord national organization for rare. It is characterized by recurrent infections, very low or undetectable levels of igg and iga, normal to increased serum igm 3, and is rare. The bodies of people with primary immunodeficiency cant get rid of germs or protect themselves from new germs as well as they should. For a discussion of genetic heterogeneity of immunodeficiency with hyper igm, see higm1 308230. It seems every time they take him off steroid he relapsesplease any one that can share information i. See related articles, an evolving view of hyper igm syndrome, and defective antigeninduced lymphocyte proliferation in the xlinked hyper igm syndrome. Hyper igm syndrome an overview sciencedirect topics.
Clinical features and genetic analysis of 20 chinese patients with. Genedx 207 perry parkway gaithersburg, md 20877 toll free. Xlinked immunodeficiency with hyper immunoglobulin m xhigm or higm1 is a rare form of primary immunodeficiency disease caused by mutations in the gene that codes for cd40 ligand cd40l, also known as cd154 and gp39. The most common form of hyper igm is xlinked hyper igm, which primarily affects boys, except in rare cases. All of them were free of severe bacterial infections, although three of them still. Pdf hyperigm syndrome type 4 with a b lymphocyteintrinsic. Hyper igm syndrome immunologic phenotype presenting with low igg, iga, and ige levels with normal or increased igm levels the term hyperigm is a misnomer igm levels are not necessarily high the relative excess of igm is due to a defect in class switch recombination csr in certain cases somatic hypermutation shm is also affected uygungil.
Aug 01, 20 symptoms and physical findings associated with hyper igm syndrome usually become apparent in the first or second year of life. Lurie childrens hospital of chicago, northwestern university feinberg school of medicine, chicago, il, usa. People with this disorder have abnormal levels of proteins called antibodies or immunoglobulins. Hyperigm syndrome type 4 is a form of hyper igm syndrome which is a defect in class switch recombination downstream of the aicda gene that does not impair somatic hyper mutation references lougaris v, badolato r, ferrari s, plebani a 2005. It is caused by the lack of heavy chain classswitching from igm to other isotypes.
The diagnosis is most often made on a clinical basis taking into consideration a complete history and physical. See related articles, an evolving view of hyperigm syndrome, and defective antigeninduced lymphocyte proliferation in the xlinked hyper igm syndrome. There was significant improvement after the immunoglobulin therapy. See also overview of immunodeficiency disorders and approach to the. It is characterized by recurrent infections, very low or undetectable levels of igg and iga, normal to increased serum igm, and is rare. Definition patients with hyper igm him syndrome have an inability to switch production. It is the most common form of hyper igm syndrome, accounting for approximately 70% of cases. B essential modulator, while autosomal recessive forms of hyper igm are caused by. Hyperigm syndrome type 4 a defect in class switch recombination downstream of the aicda gene that does not impair somatic hyper mutation.
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