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Autoimmune disease, multisystem, infantile-onset, 3(ADMIO3)

MedGen UID:
1841236
Concept ID:
C5830600
Disease or Syndrome
Synonyms: ADMIO3; CBLB DEFICIENCY
 
Gene (location): CBLB (3q13.11)
 
Monarch Initiative: MONDO:0957388
OMIM®: 620430

Definition

Infantile-onset multisystem autoimmune disease-3 (ADMIO3) is an autosomal recessive disorder of immune dysregulation characterized by the onset of various systemic autoimmune manifestations in the first months or years of life. Features may include hypothyroidism, type 1 diabetes mellitus, systemic inflammatory manifestations (fever, hepatomegaly), and autoimmune cytopenias. Laboratory studies show normal levels of T, B, and NK cells, but CD4+ (see 186940) T cells demonstrate hyperproliferation when stimulated in vitro (Janssen et al., 2022). For a discussion of genetic heterogeneity of ADMIO, see ADMIO1 (615952). [from OMIM]

Clinical features

From HPO
Recurrent lower respiratory tract infections
MedGen UID:
756211
Concept ID:
C3163798
Disease or Syndrome
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.
Autoimmune hemolytic anemia
MedGen UID:
1918
Concept ID:
C0002880
Disease or Syndrome
An autoimmune form of hemolytic anemia.
Decreased circulating IgA concentration
MedGen UID:
57934
Concept ID:
C0162538
Disease or Syndrome
Decreased levels of immunoglobulin A (IgA).
Decreased circulating total IgM
MedGen UID:
116095
Concept ID:
C0239989
Finding
An abnormally decreased level of immunoglobulin M (IgM) in blood.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Abnormal natural killer cell count
MedGen UID:
866689
Concept ID:
C4021036
Finding
Any deviation from the normal overall count of natural killer (NK) cells in the circulation or a deviation from the normal distribution of NK cell subtypes.
Abnormal T cell count
MedGen UID:
866762
Concept ID:
C4021113
Finding
A deviation from the normal count of T cells.
Abnormal B cell count
MedGen UID:
866853
Concept ID:
C4021208
Finding
A deviation from the normal count of B cells, i.e., the cells that are formed in the bone marrow, migrate to the peripheral lymphatic system, and mature into plasma cells or memory cells.
Decreased specific pneumococcal antibody level
MedGen UID:
868496
Concept ID:
C4022890
Finding
The presence of normal overall immunoglobulin levels with deficiency of specific immunoglobulins directed against pneumococci.
Increased circulating interleukin 6 concentration
MedGen UID:
901461
Concept ID:
C4280771
Finding
The concentration of interleukin-6 in the blood circulation is above the upper limit of normal.
Partial absence of specific antibody response to tetanus vaccine
MedGen UID:
1699537
Concept ID:
C5139460
Finding
A reduced ability to synthesize postvaccination antibodies against a tetanus antigen, as measured by antibody titer determination following vaccination.
Decreased circulating IgG concentration
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
Increased circulating interleukin 10 concentration
MedGen UID:
1735742
Concept ID:
C5421678
Finding
An elevation of the concentration of interleukin 10 in the blood circulation.
Hepatic hemophagocytosis
MedGen UID:
1842040
Concept ID:
C5826669
Finding
Phagocytosis of erythrocytes, lymphocytes or other hematopoietic precursors by histiocytes or macrophages observed in the liver.
Diabetes mellitus type 1
MedGen UID:
41522
Concept ID:
C0011854
Disease or Syndrome
Type 1 diabetes mellitus (T1D), also designated insulin-dependent diabetes mellitus (IDDM), is a disorder of glucose homeostasis characterized by susceptibility to ketoacidosis in the absence of insulin therapy. It is a genetically heterogeneous autoimmune disease affecting about 0.3% of Caucasian populations (Todd, 1990). Genetic studies of T1D have focused on the identification of loci associated with increased susceptibility to this multifactorial phenotype. The classic phenotype of diabetes mellitus is polydipsia, polyphagia, and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.
Urticaria
MedGen UID:
22587
Concept ID:
C0042109
Disease or Syndrome
Raised, well-circumscribed areas of erythema and edema involving the dermis and epidermis. Urticaria is intensely pruritic, and blanches completely with pressure.
Vitiligo
MedGen UID:
22677
Concept ID:
C0042900
Disease or Syndrome
Generalized well circumscribed patches of leukoderma that are generally distributed over symmetric body locations and is due to autoimmune destruction of melanocytes.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.

Recent clinical studies

Etiology

Yarom A, Rennebohm RM, Levinson JE
J Pediatr 1985 Mar;106(3):390-6. doi: 10.1016/s0022-3476(85)80662-4. PMID: 3973776

Diagnosis

Terry J, Langlois S, Rupps R, Gill H
Pediatr Dev Pathol 2020 Aug;23(4):306-311. Epub 2019 Nov 26 doi: 10.1177/1093526619890734. PMID: 31771449
Kaufman RA, Lovell DJ
Radiology 1986 Sep;160(3):741-6. doi: 10.1148/radiology.160.3.3737913. PMID: 3737913

Prognosis

Kaufman RA, Lovell DJ
Radiology 1986 Sep;160(3):741-6. doi: 10.1148/radiology.160.3.3737913. PMID: 3737913

Clinical prediction guides

Kaufman RA, Lovell DJ
Radiology 1986 Sep;160(3):741-6. doi: 10.1148/radiology.160.3.3737913. PMID: 3737913

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