X-linked-agammaglobulinaemia

Author: Brian Wu PhD. MD Candidate, Keck School of Medicine, Los Angeles, USA, Chief Editor: Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand, September 2015.


What are gamma globulins?

Gamma globulins are also called immunoglobulins. They are proteins produced by plasma cells and are essential to the body’s immune defense system. Agammaglobulinaemia means the absence of gamma globulins.

What is X-linked agammaglobulinaemia?

X-linked agammaglobulinaemia is an inherited genetic disorder first described in 1952 by Dr. Ogden Bruton. It is characterised by the body’s failure to produce mature B-lymphocytes and plasma cells. Affected patients have severe deficiencies in all immunoglobulins.

X-linked agammaglobulinaemia is also called Bruton agammaglobulinaemia.

What causes X-linked agammaglobulinaemia?

X-linked agammaglobulinaemia is caused by mutations on Bruton’s Tyrosine Kinase (BTK) gene, which was discovered in 1993. The gene normally promotes the maturation of B-lymphocytes. Since the BTK gene is found on the X-chromosome, X-linked agammaglobulinaemia presents exclusively in males. Females can present with an autosomal recessive version of agammaglobulinaemia.

Genetics of X-Linked-agammaglobulinemia

*Image courtesy Genetics 4 Medics

What are the signs and symptoms of X-linked agammaglobulinaemia?

Patients with X-linked agammaglobulinaemia may present with:

  • Reduced lymphoid or reticuloendothelial organs, including the tonsil, lymph nodes, spleen, adenoids and intestinal Peyer patches
  • Recurrent respiratory infections, including otitis media, pneumonia, bronchitis or sinusitis; the most common causes are pneumococcus, streptococcus and staphylococcus.
  • Chronic gastrointestinal symptoms, eg diarrhoea due to giardia infections
  • Skin infections

Babies with X-linked agammaglobulinaemia appear healthy at first. They begin to have recurrent infections as the protection of their mother’s antibodies wears off.

What are the risk factors for x-linked agammaglobulinemia?

The risk factors for X-linked agammaglobulinaemia include:

  • Sex. The disease presents exclusively in males.
  • Age. Patient generally begin to have symptoms between 6 and 18 months of age.
  • Family history.
  • Race. There appears to be no racial predilection.

How is x-linked agammaglobulinemia diagnosed?

X-linked agammaglobulinaemia can be diagnosed through:

  • Initial evaluation of serum immunoglobulins
  • Measurement of B-cells in peripheral blood, if initial testing reveals low serum immunoglobulins
  • Molecular analysis, involving techniques such as single-strand confirmation polymorphism, DNA analysis, denaturing gradient gel electrophoresis, or reverse transcriptase polymerase tests on the BTK gene
  • Genetic testing of the female relatives of a suspected X-linked agammaglobulinaemia patient
  • In utero testing via chorionic villus sampling or amniocentesis
  • Testing at birth for a decrease in CD19 B-cells, and an elevated level of T cells via fluorocytometric analysis

What is the treatment for x-linked agammaglobulinemia?

There is no cure for X-linked agammaglobulinaemia. However, treatment can greatly improve quality of life for X-linked agammaglobulinaemia patients.

  • Life-long immunoglobulin replacement therapy, given intravenously or subcutaneously. This helps replace antibodies an X-linked agammaglobulinaemia patient cannot make for themselves.
  • Antibiotics—sometimes used prophylactically—to reduce infection rates.
  • Abstention from live vaccines—including measles, mumps and rubella (MMR) vaccine, and the vaccines for polio, rotavirus and varicella, which can actually cause the diseases they are supposed to prevent.

 

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