Hyper-IgM syndrome without susceptibility to opportunistic infections

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ORPHA:183666OMIM:605258D80.5
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Overview

Hyper-IgM syndrome without susceptibility to opportunistic infections is a rare primary immunodeficiency characterized by normal or elevated levels of immunoglobulin M (IgM) with markedly decreased levels of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin E (IgE). Unlike other forms of hyper-IgM syndrome (such as those caused by CD40 ligand or CD40 deficiency), this subtype does not predispose patients to opportunistic infections like Pneumocystis jirovecii pneumonia or Cryptosporidium. The defect lies in the inability of B cells to undergo proper class-switch recombination, which is the process by which B cells switch from producing IgM to producing other antibody classes. This group includes forms caused by deficiencies in activation-induced cytidine deaminase (AID, encoded by the AICDA gene) and uracil-DNA glycosylase (UNG). Because the underlying defect is intrinsic to B cells rather than affecting T-cell function, cellular immunity remains intact, which explains the absence of susceptibility to opportunistic infections. Patients typically present in childhood with recurrent bacterial infections, particularly of the respiratory tract (sinusitis, otitis media, pneumonia), due to the lack of protective IgG and IgA antibodies. Lymphoid hyperplasia, including enlarged lymph nodes and tonsils, is a common feature, particularly in the AID-deficient form. Some patients may also develop autoimmune manifestations. Treatment primarily involves immunoglobulin replacement therapy (intravenous or subcutaneous) to provide the missing IgG antibodies and reduce the frequency and severity of infections. Prophylactic antibiotics may also be used. Unlike the X-linked form of hyper-IgM syndrome, hematopoietic stem cell transplantation is generally not required, as the prognosis is more favorable due to preserved cellular immunity. Regular monitoring for complications such as autoimmunity and lymphoproliferation is recommended.

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Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Childhood

Begins in childhood, roughly ages 1 to 12

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Hyper-IgM syndrome without susceptibility to opportunistic infections.

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No actively recruiting trials found for Hyper-IgM syndrome without susceptibility to opportunistic infections at this time.

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No specialists are currently listed for Hyper-IgM syndrome without susceptibility to opportunistic infections.

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Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to Hyper-IgM syndrome without susceptibility to opportunistic infections.

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Common questions about Hyper-IgM syndrome without susceptibility to opportunistic infections

What is Hyper-IgM syndrome without susceptibility to opportunistic infections?

Hyper-IgM syndrome without susceptibility to opportunistic infections is a rare primary immunodeficiency characterized by normal or elevated levels of immunoglobulin M (IgM) with markedly decreased levels of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin E (IgE). Unlike other forms of hyper-IgM syndrome (such as those caused by CD40 ligand or CD40 deficiency), this subtype does not predispose patients to opportunistic infections like Pneumocystis jirovecii pneumonia or Cryptosporidium. The defect lies in the inability of B cells to undergo proper class-switch recombination,

How is Hyper-IgM syndrome without susceptibility to opportunistic infections inherited?

Hyper-IgM syndrome without susceptibility to opportunistic infections follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Hyper-IgM syndrome without susceptibility to opportunistic infections typically begin?

Typical onset of Hyper-IgM syndrome without susceptibility to opportunistic infections is childhood. Age of onset can vary across affected individuals.