X-linked agammaglobulinemia

Source: Wikipedia, the free encyclopedia.
X-linked agammaglobulinemia
Other namesX-linked hypogammaglobulinemia, Bruton type agammaglobulinemia, Bruton syndrome, sex-linked agammaglobulinemia
X-linked recessive pattern
SpecialtyImmunology Edit this on Wikidata

X-linked agammaglobulinemia (XLA) is a rare genetic disorder discovered in 1952 that affects the body's ability to fight

BCR. Patients typically present in early childhood with recurrent infections, in particular with extracellular, encapsulated bacteria.[3] XLA is deemed to have a relatively low incidence of disease, with an occurrence rate of approximately 1 in 200,000 live births[4] and a frequency of about 1 in 100,000[5] male newborns. It has no ethnic predisposition. XLA is treated by infusion of human antibody. Treatment with pooled gamma globulin cannot restore a functional population of B cells, but it is sufficient to reduce the severity and number of infections due to the passive immunity granted by the exogenous antibodies.[3]

XLA is caused by a mutation on the

immune deficiency, and is classified with other inherited (genetic) defects of the immune system, known as primary immunodeficiency
disorders.

Signs and symptoms

Affects males 50% of the time if mother is a carrier for the gene. Children are generally asymptomatic until 6–9 months of age when maternal IgG decreases. Present with recurrent infections with Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, hepatitis virus, and enterovirus CNS infections.[7] Examination shows lymphoid hypoplasia (tonsils and adenoids, no splenomegaly or lymphadenopathy). There is significant decrease in all immunoglobulins.[citation needed]

Genetics

X-chromosome

Most antibodies are gamma globulins. Antibodies are made mainly by plasma cells, which are daughter cells of the B cell line. The Btk enzyme plays an essential role in the maturation of B cells in the bone marrow, and when mutated, immature pro-B lymphocytes are unable to develop into pre-B lymphocytes, which normally develop into mature (naive) B cells that leave the bone marrow into the blood stream.[citation needed]

The disorder is inherited in an

carriers.[3] This is because males have only one copy of the X chromosome, while females have two copies; one normal copy of an X chromosome can compensate for mutations in the other X chromosome, so they are less likely to be symptomatic.[citation needed
]

There is 30–50% chance of XLA patients having a positive family history of genetic inheritance. The rest of the cases occur as random mutations.[4] If a carrier female gives birth to a male child, there is a 50% chance that the male will have XLA. A carrier female has a 25% chance overall of giving birth to an affected male child. An XLA patient will pass on the gene, and all of his daughters will be XLA carriers, meaning that any male grandchildren from an XLA patient's daughters have a 50% chance of inheriting XLA. A female XLA patient can arise only as the child of an XLA patient and a carrier mother. XLA can also rarely result from a spontaneous mutation in the fetus of a non-carrier mother.[citation needed]

Diagnosis

XLA diagnosis usually begins due to a history of recurrent infections, mostly in the

IgD.[3]

When XLA is suspected, it is possible to do a

Western Blot test to determine whether the Btk protein is being expressed. Results of a genetic blood test confirm the diagnosis and will identify the specific Btk mutation,[3] however its cost prohibits its use in routine screening for all pregnancies. Women with an XLA patient in their family should seek genetic counseling before pregnancy. Although the symptoms of a XLA and other primary immune diseases (PID) include repeated and often severe infections, the average time for a diagnosis of a PID can be up to 10 years.[citation needed
]

Treatment

The most common treatment for XLA is an

IgG blood count exceeds 800 mg/kg. The dose is based on the patient's weight and IgG blood-count.[citation needed
]

Muscle injections of immunoglobulin (IMIg) were common before IVIg was prevalent, but are less effective and much more painful; hence, IMIg is now uncommon.

U.S. Food and Drug Administration (FDA), which is recommended in cases of severe adverse reactions to the IVIg treatment.[citation needed
]

Antibiotics are another common supplementary treatment. Local antibiotic treatment (drops, lotions) are preferred over systemic treatment (pills) for long-term treatment, if possible. One of the future prospects of XLA treatment is gene therapy, which could potentially cure XLA. Gene therapy technology is still in its infancy and may cause severe complications such as cancer and even death. Moreover, the long-term success and complications of this treatment are, as yet, unknown.[citation needed
]

Other considerations

It is not recommended and dangerous for XLA patients to receive live attenuated

immune memory.[citation needed
]

XLA patients are specifically susceptible to viruses of the

B cells (and so HLA co-receptors) needed for the viral infection.[8] Patients with XLA are also more likely to have a history of septic arthritis.[4]

It is not known if XLA patients are able to generate an

autoimmune
illnesses.

Agammaglobulinemia (XLA) is similar to the primary immunodeficiency disorder Hypogammaglobulinemia (CVID), and their clinical conditions and treatment are almost identical. However, while XLA is a congenital disorder, with known genetic causes, CVID may occur in adulthood and its causes are not yet understood. In addition, to X-linked agammaglobulinemia a couple of autosomal recessive agammaglobulinemia gene mutations have been described including mutations in IGHM,[9] IGLL1,[10] CD79A/B,[11][12] BLNK [13] and deletion of the deletion of the terminal 14q32.33 chromosom.[14]

XLA was also historically mistaken as

Severe Combined Immunodeficiency (SCID), a much more severe immune deficiency ("Bubble boys").A strain of laboratory mouse, XID, is used to study XLA. These mice have a mutated version of the mouse Btk gene, and exhibit a similar, yet milder, immune deficiency as in XLA.[citation needed
]

See also

References

  1. ISBN 0-7216-2921-0
    .
  2. ^ "X-linked Agammaglobulinemia: Immunodeficiency Disorders: Merck Manual Professional". Retrieved 2008-03-01.
  3. ^ a b c d e f g h i X-Linked Agammaglobulinemia Patient and Family Handbook for The Primary Immune Diseases. Third Edition. 2001. Published by the Immune Deficiency Foundation
  4. ^
    PMID 18306466
    .
  5. ISBN 978-0-07-147173-2
    .
  6. PMID 9651432
    .
  7. ^ Grammatikos Alexandros, Donati Matthew, Johnston Sarah L., Gompels Mark M. Peripheral B Cell Deficiency and Predisposition to Viral Infections: The Paradigm of Immune Deficiencies. Frontiers in Immunology (12)2021 https://www.frontiersin.org/articles/10.3389/fimmu.2021.731643 DOI=10.3389/fimmu.2021.731643
  8. PMID 9882361
    .
  9. ^ "OMIM Entry - # 601495 - AGAMMAGLOBULINEMIA 1, AUTOSOMAL RECESSIVE; AGM1".
  10. ^ "OMIM Entry - # 613500 - AGAMMAGLOBULINEMIA 2, AUTOSOMAL RECESSIVE; AGM2".
  11. ^ "OMIM Entry - # 613501 - AGAMMAGLOBULINEMIA 3, AUTOSOMAL RECESSIVE; AGM3".
  12. ^ "OMIM Entry - # 612692 - AGAMMAGLOBULINEMIA 6, AUTOSOMAL RECESSIVE; AGM6".
  13. ^ "OMIM Entry - # 613502 - AGAMMAGLOBULINEMIA 4, AUTOSOMAL RECESSIVE; AGM4".
  14. PMID 28705765
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=X-linked_agammaglobulinemia&oldid=1140553073"