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Combined immunodeficiency due to ORAI1 deficiency(IMD9)

MedGen UID:
440578
Concept ID:
C2748568
Disease or Syndrome
Synonyms: Immune dysfunction with T-cell inactivation due to calcium entry defect 1; IMMUNODEFICIENCY 9
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ORAI1 (12q24.31)
 
Monarch Initiative: MONDO:0013007
OMIM®: 612782
Orphanet: ORPHA317428

Definition

Immunodeficiency-9 (IMD9) is an autosomal recessive disorder characterized by early onset of recurrent infections due to defective T-cell activation. Affected individuals also have congenital myopathy resulting in muscle weakness as well as features of ectodermal dysplasia, including soft dental enamel (summary by McCarl et al., 2009). [from OMIM]

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
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.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Amelogenesis imperfecta
MedGen UID:
240
Concept ID:
C0002452
Congenital Abnormality
A developmental dysplasia of the dental enamel.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Gowers sign
MedGen UID:
65865
Concept ID:
C0234182
Finding
A phenomenon whereby patients are not able to stand up without the use of the hands owing to weakness of the proximal muscles of the lower limbs.
Respiratory insufficiency due to muscle weakness
MedGen UID:
812797
Concept ID:
C3806467
Finding
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.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Stomatitis
MedGen UID:
52511
Concept ID:
C0038362
Disease or Syndrome
Stomatitis is an inflammation of the mucous membranes of any of the structures in the mouth.
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 infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Hypoplasia of the thymus
MedGen UID:
146347
Concept ID:
C0685891
Congenital Abnormality
Underdevelopment of the thymus.
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.
BCGitis
MedGen UID:
1684722
Concept ID:
C5139070
Disease or Syndrome
Local or regional infection with Bacillus Calmette-Guerin (BCG) following vaccination.
Decreased circulating IgG concentration
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
Heat intolerance
MedGen UID:
66659
Concept ID:
C0231274
Pathologic Function
The inability to maintain a comfortable body temperature in warm or hot weather.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.
Recurrent aphthous stomatitis
MedGen UID:
445425
Concept ID:
C2937365
Disease or Syndrome
Recurrent episodes of ulceration of the oral mucosa, typically presenting as painful, sharply circumscribed fibrin-covered mucosal defects with a hyperemic border.
Ectodermal dysplasia
MedGen UID:
8544
Concept ID:
C0013575
Disease or Syndrome
Ectodermal dysplasia is a group of conditions in which there is abnormal development of the skin, hair, nails, teeth, or sweat glands.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCombined immunodeficiency due to ORAI1 deficiency
Follow this link to review classifications for Combined immunodeficiency due to ORAI1 deficiency in Orphanet.

Recent clinical studies

Etiology

Dellis O, Mercier P, Chomienne C
BMC Pharmacol 2011 Jan 26;11:1. doi: 10.1186/1471-2210-11-1. PMID: 21266088Free PMC Article

Diagnosis

Deveci K, Esenboğa S, Bildik HN, Ocak M, Gülşen HH, Ertuğrul İ, Oğuz KK, Çağdaş D, Yalnızoğlu D, Tezcan İ
Turk J Pediatr 2023;65(4):698-703. doi: 10.24953/turkjped.2022.721. PMID: 37661687
Alonso L, Méndez-Echevarría A, Rudilla F, Mozo Y, Soler-Palacin P, Sisinni L, Bueno D, Riviere J, de Paz R, Sánchez-Zapardiel E, Querol S, Rodriguez-Pena R, López-Granados E, Gimeno R, Díaz de Heredia C, Pérez-Martínez A
J Clin Immunol 2021 May;41(4):748-755. Epub 2021 Jan 18 doi: 10.1007/s10875-020-00961-w. PMID: 33462728
Mendez-Echevarria A, Gonzalez-Granado LI, Allende LM, De Felipe B, Teresa DR, Calvo C, Perez-Martinez A, Raquel RG, Neth O
Pediatr Infect Dis J 2019 Feb;38(2):157-160. doi: 10.1097/INF.0000000000002058. PMID: 29613974
Dellis O, Mercier P, Chomienne C
BMC Pharmacol 2011 Jan 26;11:1. doi: 10.1186/1471-2210-11-1. PMID: 21266088Free PMC Article

Therapy

Alonso L, Méndez-Echevarría A, Rudilla F, Mozo Y, Soler-Palacin P, Sisinni L, Bueno D, Riviere J, de Paz R, Sánchez-Zapardiel E, Querol S, Rodriguez-Pena R, López-Granados E, Gimeno R, Díaz de Heredia C, Pérez-Martínez A
J Clin Immunol 2021 May;41(4):748-755. Epub 2021 Jan 18 doi: 10.1007/s10875-020-00961-w. PMID: 33462728

Prognosis

Mendez-Echevarria A, Gonzalez-Granado LI, Allende LM, De Felipe B, Teresa DR, Calvo C, Perez-Martinez A, Raquel RG, Neth O
Pediatr Infect Dis J 2019 Feb;38(2):157-160. doi: 10.1097/INF.0000000000002058. PMID: 29613974
Lian J, Cuk M, Kahlfuss S, Kozhaya L, Vaeth M, Rieux-Laucat F, Picard C, Benson MJ, Jakovcevic A, Bilic K, Martinac I, Stathopulos P, Kacskovics I, Vraetz T, Speckmann C, Ehl S, Issekutz T, Unutmaz D, Feske S
J Allergy Clin Immunol 2018 Oct;142(4):1297-1310.e11. Epub 2017 Nov 16 doi: 10.1016/j.jaci.2017.10.031. PMID: 29155098Free PMC Article
Derler I, Fahrner M, Carugo O, Muik M, Bergsmann J, Schindl R, Frischauf I, Eshaghi S, Romanin C
J Biol Chem 2009 Jun 5;284(23):15903-15. Epub 2009 Apr 14 doi: 10.1074/jbc.M808312200. PMID: 19366689Free PMC Article
Thompson JL, Mignen O, Shuttleworth TJ
J Biol Chem 2009 Mar 13;284(11):6620-6. Epub 2008 Dec 15 doi: 10.1074/jbc.M808346200. PMID: 19075015Free PMC Article

Clinical prediction guides

Mendez-Echevarria A, Gonzalez-Granado LI, Allende LM, De Felipe B, Teresa DR, Calvo C, Perez-Martinez A, Raquel RG, Neth O
Pediatr Infect Dis J 2019 Feb;38(2):157-160. doi: 10.1097/INF.0000000000002058. PMID: 29613974
Dellis O, Mercier P, Chomienne C
BMC Pharmacol 2011 Jan 26;11:1. doi: 10.1186/1471-2210-11-1. PMID: 21266088Free PMC Article
Derler I, Fahrner M, Carugo O, Muik M, Bergsmann J, Schindl R, Frischauf I, Eshaghi S, Romanin C
J Biol Chem 2009 Jun 5;284(23):15903-15. Epub 2009 Apr 14 doi: 10.1074/jbc.M808312200. PMID: 19366689Free PMC Article
Thompson JL, Mignen O, Shuttleworth TJ
J Biol Chem 2009 Mar 13;284(11):6620-6. Epub 2008 Dec 15 doi: 10.1074/jbc.M808346200. PMID: 19075015Free PMC Article

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