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Non-syndromic agammaglobulinemia

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Disease definition

Isolated agammaglobulinemia (IA) is the non-syndromic form of agammaglobulinemia, a primary immunodeficiency disease, and is characterized by deficient gamma globulins and associated predisposition to frequent and recurrent infections from infancy.

ORPHA:229717

Classification level: Disorder

Synonym(s):
  • Non-syndromic hypogammaglobulinemia

Source: PubMed ID 34241796 36198931

Prevalence: 1-9 / 1 000 000

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive

Age of onset: Infancy, Neonatal

ICD-10: D80.0

ICD-11: 4A01.00

OMIM: 300310 300755 601495 612692 613500 613501 613502 613506 615214 616941

UMLS: C4707181

Summary
Epidemiology

Prevalence is estimated to be about 1/250,000 to 1/500/000. Isolated agammaglobulinemia has been reported worldwide in all ethnic groups.

Clinical description

Two forms of IA have been described based on the pattern of inheritance of the genetic defects underlying the disorder: X-linked agammaglobulinemia (XLA) which represents approximately 85% of the affected patients, and autosomal agammaglobulinemia which includes recessive and dominant cases but is far less frequent. The clinical signs of the two forms are very similar and include recurrent bacterial infections (otitis media, pneumonia, and sinusitis), diarrhea and skin infections with onset in infancy. Late-onset agammaglobulinemia is known as common variable immunodeficiency (CVID).

Etiology

Defects in B lymphocyte development and maturation appear to underlie agammaglobulinemia. Mutations in seven genes have been reported to be related to IA: BTK (Xq21.33-q22), BLNK (10q23.2-q23.33), CD79A (19q13.2), CD79B (17q23), IGHM(14q32.33), IGLL1 (22q11.23), PIK3R1 (5q13.1) and TCF3 (19p13.3).

Genetic counseling

X-linked, autosomal recessive and autosomal dominant cases are reported.

Last update: December 2013
A summary on this disease is available in Français, Español, Deutsch, Nederlands
Detailed information

Logo ERN: produced/endorsed by ERN(s) Logo FSMR: produced/endorsed by FSMR(s)

Guidelines
Emergency guidelines
Français (2020.pdf) - Orphanet Urgences
Clinical practice guidelines
Disease review articles
Clinical genetics review
English (2024) - GeneReviews
The documents contained in this website are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.