X-Linked Agammaglobulinemia – Symptoms and Causes
Overview
X-linked agammaglobulinemia (XLA) is an inherited immune system disorder that primarily affects males. This condition weakens the body’s ability to fight infections, making patients vulnerable to frequent illnesses.
Most diagnoses occur during infancy or early childhood after a pattern of recurring infections becomes evident. Some cases remain undetected until adulthood.
While females rarely develop the condition, they can carry the genetic mutation and pass it to their male children.
Symptoms
People with X-linked agammaglobulinemia (XLA) typically develop symptoms during early childhood. Most babies appear healthy for the first 6-9 months because they still have protective antibodies from their mothers. Once these maternal antibodies decrease, symptoms begin to appear.
The main symptom of XLA is frequent infections. These often affect:
- Inner ears
- Sinuses
- Respiratory tract
- Bloodstream
- Internal organs
Children with XLA may get sick more than 8-12 times per year. These infections can be severe and don’t respond well to normal treatments.
Common infections in XLA patients include:
- Pneumonia
- Bronchitis
- Sinusitis
- Ear infections (otitis media)
- Conjunctivitis
- Skin infections
- Gastrointestinal infections
Unusual germs may cause these infections. Bacteria that rarely trouble healthy people can cause serious illness in those with XLA.
Physical growth may slow down in affected children. Without proper treatment, they might be smaller than their peers. Some patients develop a distinctive pattern of skin rashes.
Boys with XLA have very small tonsils and lymph nodes because these structures need B cells to develop properly.
Causes
X-linked agammaglobulinemia (XLA) happens because of a genetic mutation. This mutation affects the BTK gene, which sits on the X chromosome.
The BTK gene gives instructions for making Bruton tyrosine kinase, a protein that B cells need to develop properly.
When this gene has a mutation, B cells can’t mature normally. Without mature B cells, the body can’t make enough antibodies to fight infections.
Boys inherit XLA from their mothers, who carry the faulty gene but usually show no symptoms.
Since XLA links to the X chromosome, it mainly affects males. Girls have two X chromosomes, so even if one has the mutation, the other healthy chromosome often prevents the disease.
Boys have only one X chromosome, so if it carries the mutation, they will develop XLA.
About 30-50% of XLA cases come from new mutations. This means neither parent carried the gene beforehand. The remaining cases pass down through families, following an X-linked recessive pattern.
Complications
Children with X-linked agammaglobulinemia (XLA) face several serious health challenges.
Lung problems are especially common. Repeated respiratory infections can lead to bronchiectasis, a condition where the airways become permanently widened and scarred. This makes it harder to clear mucus and increases the risk of more infections.
Digestive system complications may include:
- Chronic diarrhea
- Poor nutrient absorption
- Growth problems in children
The risk of certain cancers might be higher in XLA patients, particularly lymphomas and leukemias. This happens because the immune system plays a role in detecting and destroying abnormal cells.
Brain and nervous system issues can develop in some cases. Infections may spread to the brain, causing encephalitis or meningitis. Some patients also develop a condition similar to multiple sclerosis.
Joint inflammation resembling arthritis affects about 20% of people with XLA. This can cause pain, swelling, and limited movement in affected joints.
