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Immunodeficiency 115 with autoinflammation(IMD115)

MedGen UID:
1847791
Concept ID:
C5882724
Disease or Syndrome
Synonym: IMD115
 
Gene (location): RNF31 (14q12)
 
Monarch Initiative: MONDO:0957981
OMIM®: 620632

Definition

Immunodeficiency-115 with autoinflammation (IMD115) is an autosomal recessive disorder characterized by the onset of symptoms of immune dysregulation in early infancy. Affected individuals have immunodeficiency with recurrent bacterial, viral, and fungal infections, as well as autoinflammatory features, including arthritis and dermatitis. Some patients may have more systemic involvement, such as myopathy, gastrointestinal abnormalities, and anemia. Laboratory studies show variable B-cell and T-cell defects, sometimes with defective antibody responses and hypogammaglobulinemia (Boisson et al., 2015; Oda et al., 2019). [from OMIM]

Clinical features

From HPO
Verrucae
MedGen UID:
777120
Concept ID:
C3665596
Finding
Warts, benign growths on the skin or mucous membranes that cause cosmetic problems as well as pain and discomfort. Warts most often occur on the hands, feet, and genital areas.
Clubbing
MedGen UID:
57692
Concept ID:
C0149651
Anatomical Abnormality
Broadening of the soft tissues (non-edematous swelling of soft tissues) of the digital tips in all dimensions associated with an increased longitudinal and lateral curvature of the nails.
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
Postnatal growth retardation
MedGen UID:
395343
Concept ID:
C1859778
Finding
Slow or limited growth after birth.
Intermittent diarrhea
MedGen UID:
66782
Concept ID:
C0239181
Sign or Symptom
Repeated episodes of diarrhea separated by periods without diarrhea.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Fatty replacement of skeletal muscle
MedGen UID:
866735
Concept ID:
C4021082
Finding
Muscle fibers degeneration resulting in fatty replacement of skeletal muscle fibers
Eczematoid dermatitis
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.
Immunodeficiency
MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
Intestinal lymphangiectasia
MedGen UID:
9828
Concept ID:
C0024215
Disease or Syndrome
Angiectasia of lymph vessels (i.e., dilatation of lymphatic vessels) in the intestines.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Esophageal candidiasis
MedGen UID:
66784
Concept ID:
C0239295
Disease or Syndrome
Candida infections of the esophagus are considered opportunistic infections and are seen most commonly in immunosuppressed patients, the most common symptoms being dysphagia, odynophagia, and retrosternal pain.
Recurrent viral infections
MedGen UID:
332357
Concept ID:
C1837066
Finding
Increased susceptibility to viral infections, as manifested by recurrent episodes of viral infection.
Recurrent bacterial infections
MedGen UID:
334943
Concept ID:
C1844383
Finding
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.
T lymphocytopenia
MedGen UID:
419385
Concept ID:
C2931322
Finding
An abnormally low count of T cells.
Reduced antigen-specific T cell proliferation
MedGen UID:
1621145
Concept ID:
C4531148
Finding
Impaired proliferation and expansion of a T cell population following activation by an antigenic stimulus.
Superficial dermal perivascular inflammatory infiltrate
MedGen UID:
1620848
Concept ID:
C4531290
Anatomical Abnormality
Numerous lymphocytes surrounding blood vessels in the superficial part of the dermis.
Decreased proportion of memory T cells
MedGen UID:
1689962
Concept ID:
C5139180
Finding
An abnormally reduced proportion of memory T cells compared to the total number of T cells in the blood.
Partial absence of specific antibody response to unconjugated pneumococcus vaccine
MedGen UID:
1686478
Concept ID:
C5139464
Finding
A reduced ability to synthesize postvaccination antibodies against a pneumococcus antigen, as measured by antibody titer determination following vaccination.
Partial absence of specific antibody response to Haemophilus influenzae type b (Hib) vaccine
MedGen UID:
1706490
Concept ID:
C5139468
Finding
A reduced ability to synthesize postvaccination antibodies against a Haemophilus influenzae type b (Hib) 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.
Elevated erythrocyte sedimentation rate
MedGen UID:
57727
Concept ID:
C0151632
Finding
An increased erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen.
Hypoalbuminemia
MedGen UID:
68694
Concept ID:
C0239981
Finding
Reduction in the concentration of albumin in the blood.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.
Abnormal circulating creatine kinase concentration
MedGen UID:
868058
Concept ID:
C4022449
Finding
Any deviation from the normal circulating creatine kinase concentration.
Elevated circulating C-reactive protein concentration
MedGen UID:
892906
Concept ID:
C4023452
Finding
An abnormal elevation of the C-reactive protein level in the blood circulation.
Elevated haptoglobin level
MedGen UID:
1698119
Concept ID:
C5209263
Finding
An abnormally high concentration of haptoglobin in the blood circulation. Haptoglobin is an acute-phase reactant whose levels can become elevated in the presence of infection and inflammation.
Neonatal omphalitis
MedGen UID:
510678
Concept ID:
C0158947
Disease or Syndrome
An infection of the umbilicus and/or surrounding tissues occurring in the neonatal period.

Recent clinical studies

Etiology

Staus P, Rusch S, El-Helou S, Müller G, Krausz M, Geisen U, Caballero-Oteyza A, Krüger R, Bakhtiar S, Lee-Kirsch MA, Fasshauer M, Baumann U, Hoyer BF, Farela Neves J, Borte M, Carrabba M, Hauck F, Ehl S, Bader P, von Bernuth H, Atschekzei F, Seppänen MRJ, Warnatz K, Nieters A, Kindle G, Grimbacher B
J Clin Immunol 2023 Aug;43(6):1289-1301. Epub 2023 Apr 21 doi: 10.1007/s10875-023-01472-0. PMID: 37084016Free PMC Article

Diagnosis

Staus P, Rusch S, El-Helou S, Müller G, Krausz M, Geisen U, Caballero-Oteyza A, Krüger R, Bakhtiar S, Lee-Kirsch MA, Fasshauer M, Baumann U, Hoyer BF, Farela Neves J, Borte M, Carrabba M, Hauck F, Ehl S, Bader P, von Bernuth H, Atschekzei F, Seppänen MRJ, Warnatz K, Nieters A, Kindle G, Grimbacher B
J Clin Immunol 2023 Aug;43(6):1289-1301. Epub 2023 Apr 21 doi: 10.1007/s10875-023-01472-0. PMID: 37084016Free PMC Article

Clinical prediction guides

Staus P, Rusch S, El-Helou S, Müller G, Krausz M, Geisen U, Caballero-Oteyza A, Krüger R, Bakhtiar S, Lee-Kirsch MA, Fasshauer M, Baumann U, Hoyer BF, Farela Neves J, Borte M, Carrabba M, Hauck F, Ehl S, Bader P, von Bernuth H, Atschekzei F, Seppänen MRJ, Warnatz K, Nieters A, Kindle G, Grimbacher B
J Clin Immunol 2023 Aug;43(6):1289-1301. Epub 2023 Apr 21 doi: 10.1007/s10875-023-01472-0. PMID: 37084016Free PMC Article

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