MYD88 deficiency

Other Names: Pyogenic bacterial infections due to MyD88 deficiency; Bacterial susceptibility due to TLR signaling pathway deficiency

MYD88 deficiency is a rare primary immunodeficiency characterized by an increased susceptibility to certain types of bacterial infections. This primary immunodeficiency affects the innate immune response, which is the body's early, nonspecific response to foreign invaders (pathogens). MyD88 deficiency leads to abnormally frequent and severe infections by a subset of bacteria known as pyogenic bacteria. (Infection with pyogenic bacteria causes the production of pus.) However, affected individuals have normal resistance to other common bacteria, viruses, fungi, and parasites.

Epidemiology

The prevalence of MyD88 deficiency is unknown. At least 24 affected individuals have been described in the medical literature.

Cause

MyD88 deficiency is caused by mutations in the MYD88 gene, which provides instructions for making a protein that plays an important role in stimulating the immune system to respond to bacterial infection. The MyD88 protein is part of a signaling pathway that is involved in early recognition of pathogens and the initiation of inflammation to fight infection. This signaling pathway is part of the innate immune response.

Mutations in the MYD88 gene lead to the production of a nonfunctional protein or no protein at all. The loss of functional MyD88 protein prevents the immune system from triggering inflammation in response to pathogens that would normally help fight the infections. Because the early immune response is insufficient, bacterial infections occur often and become severe and invasive.

Researchers suggest that as the immune system matures, other systems compensate for the loss of MyD88 protein, accounting for the improvement in the condition that occurs by adolescence.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

The most common infections in MyD88 deficiency are caused by the Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa bacteria. Most people with this condition have their first bacterial infection before age 2, and the infections can be life-threatening in infancy and childhood. Infections become less frequent by about age 10.

Children with MyD88 deficiency develop invasive bacterial infections, which can involve the blood (septicemia), the membrane covering the brain and spinal cord (meningitis), or the joints (leading to inflammation and arthritis). Invasive infections can also cause areas of tissue breakdown and pus production (abscesses) on internal organs. In addition, affected individuals can have localized infections of the ears, nose, or throat. Although fever is a common reaction to bacterial infections, many people with MyD88 deficiency do not at first develop a high fever in response to these infections, even if the infection is severe.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Immunodeficiency(Decreased immune function)

30%-79% of people have these symptoms

• Recurrent bacterial skin infections

5%-29% of people have these symptoms

• Fever

1%-4% of people have these symptoms

• Abscess
• B lymphocytopenia(Low B cell count)
• Delayed umbilical cord separation
• Recurrent meningitis
• Recurrent skin infections(Skin infections, recurrent)
• Sepsis(Infection in blood stream)
• Septic arthritis

Diagnosis

Clinical tests Molecular Genetics Tests Targeted variant analysis Sequence analysis of the entire coding region Deletion/duplication analysis

Treatment

Management is focused on the prevention and early treatment of infections with appropriate antibiotics.

NIH genetic and rare disease info

• NIH info on MYD88 deficiency

MYD88 deficiency is a rare disease.

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