X-linked agammaglobulinemia

General Information (adopted from Orphanet):

Synonyms, Signs: Bruton type agammaglobulinemia
BTK-deficiency
Number of Symptoms 30
OrphanetNr: 47
OMIM Id: 300310
300755
ICD-10: D80.0
UMLs: C0221026
MeSH: C537409
MedDRA: 10060360
Snomed: 65880007

Prevalence, inheritance and age of onset:

Prevalence: 0.1 of 100 000 [Orphanet]
Inheritance: X-linked recessive
Not applicable
[Orphanet]
Age of onset: Childhood
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Isolated agammaglobulinemia
 -Rare genetic disease
 -Rare immune disease

Symptom Information: Sort by abundance 

1
(HPO:0000246) Sinusitis Very frequent [Orphanet] 73 / 7739
2
(HPO:0100533) Inflammatory abnormality of the eye Very frequent [Orphanet] 70 / 7739
3
(HPO:0000389) Chronic otitis media Very frequent [Orphanet] 64 / 7739
4
(HPO:0001287) Meningitis Frequent [Orphanet] 46 / 7739
5
(HPO:0100769) Synovitis Frequent [Orphanet] 86 / 7739
6
(HPO:0002754) Osteomyelitis Occasional [Orphanet] 37 / 7739
7
(HPO:0002024) Malabsorption Occasional [Orphanet] 142 / 7739
8
(HPO:0001396) Cholestasis Occasional [Orphanet] 136 / 7739
9
(HPO:0002014) Diarrhea Very frequent [Orphanet] 225 / 7739
10
(HPO:0004325) Decreased body weight Occasional [Orphanet] 492 / 7739
11
(HPO:0004322) Short stature Very frequent [Orphanet] 1232 / 7739
12
(HPO:0000988) Skin rash Very frequent [Orphanet] 98 / 7739
13
(HPO:0100838) Recurrent cutaneous abscess formation Very frequent [Orphanet] 15 / 7739
14
(HPO:0200042) Skin ulcer Very frequent [Orphanet] 138 / 7739
15
(HPO:0001053) Hypopigmented skin patches Occasional [Orphanet] 80 / 7739
16
(HPO:0001596) Alopecia Occasional [Orphanet] 162 / 7739
17
(HPO:0001903) Anemia Occasional [Orphanet] 289 / 7739
18
(HPO:0001873) Thrombocytopenia Occasional [Orphanet] 224 / 7739
19
(HPO:0010701) Abnormal immunoglobulin level Very frequent [Orphanet] 49 / 7739
20
(HPO:0001874) Abnormality of neutrophils Frequent [Orphanet] 47 / 7739
21
(HPO:0001945) Fever Very frequent [Orphanet] 218 / 7739
22
(HPO:0002205) Recurrent respiratory infections Very frequent [Orphanet] 254 / 7739
23
(HPO:0010978) Abnormality of immune system physiology Very frequent [Orphanet] 148 / 7739
24
(HPO:0100806) Sepsis Frequent [Orphanet] 48 / 7739
25
(HPO:0002960) Autoimmunity Occasional [Orphanet] 78 / 7739
26
(HPO:0100765) Abnormality of the tonsils Very frequent [Orphanet] 10 / 7739
27
(HPO:0100763) Abnormality of the lymphatic system Very frequent [Orphanet] 18 / 7739
28
(HPO:0001324) Muscle weakness Very frequent [Orphanet] 859 / 7739
29
(HPO:0003549) Abnormality of connective tissue Frequent [Orphanet] 22 / 7739
30
(HPO:0001522) Death in infancy Occasional [Orphanet] 275 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Diagnosis GeneReviews The following diagnostic criteria for X-linked agammoglobulinemia were published in 1999. There is an ongoing effort to update the diagnostic criteria (for all inherited immunodeficiencies) but no updates have been published [Conley et al 1999]. ...
Clinical Description GeneReviews Individuals with X-linked agammaglobulinemia (XLA) are usually well for the first few months of life because they are protected by transplacentally acquired maternal immunoglobulin. Typically, affected males develop recurrent bacterial infections in the first two years of life and are recognized as having immunodeficiency before age five years [Conley & Howard 2002, Plebani et al 2002]. The most common infecting organisms include H influenzae and S pneumoniae. Approximately 10% of individuals with mutations in BTK are not recognized as having immunodeficiency until after age ten years and some not until adulthood [Howard et al 2006, Conley et al 2008]. Some patients have higher serum immunoglobulin concentrations than expected, but all have very low numbers of B cells....
Genotype-Phenotype Correlations GeneReviews No strong correlation is observed between the specific mutation in BTK and the severity of disease; however, individuals who have amino acid substitutions or splice defects that occur at sites that are conserved, but not invariant, tend to be older at the time of diagnosis, and they have higher serum concentrations of IgM and slightly more B cells in the peripheral circulation [López-Granados et al 2005, Broides et al 2006]. ...
Differential Diagnosis GeneReviews Approximately 90% of males who are presumed to have X-linked agammaglobulinemia (XLA) based on early onset of infections, severe hypogammaglobulinemia, and markedly reduced numbers of B cells have detectable mutations in BTK [Conley et al 1998]....
Management GeneReviews A patient with XLA should receive specialty care at a center with expertise in this disorder. ...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....