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Combined immunodeficiency due to MALT1 deficiency(IMD12)

MedGen UID:
815913
Concept ID:
C3809583
Disease or Syndrome
Synonym: Immunodeficiency 12
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): MALT1 (18q21.32)
 
Monarch Initiative: MONDO:0014197
OMIM®: 615468
Orphanet: ORPHA397964

Definition

Combined immunodeficiency due to MALT1 deficiency is a rare, genetic form of primary immunodeficiency characterized by growth retardation, early recurrent pulmonary infections leading to bronchiectasis, inflammatory gastrointestinal disease, and other symptoms, such as rash, dermatitis, skin infections. [from ORDO]

Clinical features

From HPO
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.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Decreased body weight
MedGen UID:
1806755
Concept ID:
C5574742
Finding
Abnormally low body weight.
Esophageal stricture
MedGen UID:
1637009
Concept ID:
C4551650
Disease or Syndrome
A pathological narrowing of the esophagus that is caused by the development of a ring of scar tissue that constricts the esophageal lumen.
Mastoiditis
MedGen UID:
7480
Concept ID:
C0024904
Disease or Syndrome
Inflammation of the mucosal lining of the mastoid antrum and mastoid air cell system of the mastoid process.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Bronchiectasis
MedGen UID:
14234
Concept ID:
C0006267
Disease or Syndrome
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
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.
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.
Abnormal lymphocyte count
MedGen UID:
663425
Concept ID:
C0580550
Finding
Any abnormality in the total number of lymphocytes in the blood.
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.
Decreased lymphocyte proliferation in response to anti-CD3
MedGen UID:
1614554
Concept ID:
C4531165
Finding
A decreased proliferative response of lymphocytes in vitro or in vivo, when stimulated with an anti-CD3 antibody against the T-cell co-receptor, CD3.
Absent isohemagglutinin level
MedGen UID:
1691361
Concept ID:
C5139456
Finding
Absent or undetectable level of isohemagglutinin. An isohemagglutinin refers to the naturally occurring antibodies in the ABO blood group system (i.e., anti-A in a group B person, anti-B in a group A person, and anti-A, anti-B, and anti-A,B in a group O person).
Complete or near-complete absence of specific antibody response to tetanus vaccine
MedGen UID:
1687415
Concept ID:
C5139458
Finding
The inability to synthesize postvaccination antibodies against a tetanus antigen, as measured by antibody titer determination following vaccination.
Skin rash
MedGen UID:
1830322
Concept ID:
C5779628
Sign or Symptom
A red eruption of the skin.
Cheilitis
MedGen UID:
3349
Concept ID:
C0007971
Disease or Syndrome
Inflammation of the lip.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCombined immunodeficiency due to MALT1 deficiency
Follow this link to review classifications for Combined immunodeficiency due to MALT1 deficiency in Orphanet.

Recent clinical studies

Etiology

Charbit-Henrion F, Jeverica AK, Bègue B, Markelj G, Parlato M, Avčin SL, Callebaut I, Bras M, Parisot M, Jazbec J, Homan M, Ihan A, Rieux-Laucat F, Stolzenberg MC, Ruemmele FM, Avčin T, Cerf-Bensussan N; GENIUS Group
J Pediatr Gastroenterol Nutr 2017 Mar;64(3):378-384. doi: 10.1097/MPG.0000000000001262. PMID: 27253662
Turvey SE, Durandy A, Fischer A, Fung SY, Geha RS, Gewies A, Giese T, Greil J, Keller B, McKinnon ML, Neven B, Rozmus J, Ruland J, Snow AL, Stepensky P, Warnatz K
J Allergy Clin Immunol 2014 Aug;134(2):276-84. doi: 10.1016/j.jaci.2014.06.015. PMID: 25087226Free PMC Article

Diagnosis

El Hawary R, Meshaal S, Lotfy S, Abd Elaziz D, Eldash AS, Erfan A, Alkady R, Darwish R, Saad M, Chohayeb E, Galal N, Elmarsafy AM
Immunol Res 2024 Oct;72(5):1147-1153. Epub 2024 Jul 17 doi: 10.1007/s12026-024-09517-1. PMID: 39017781
Lu HY, Biggs CM, Blanchard-Rohner G, Fung SY, Sharma M, Turvey SE
J Allergy Clin Immunol 2019 May;143(5):1661-1673. doi: 10.1016/j.jaci.2019.03.009. PMID: 31060714
Frizinsky S, Rechavi E, Barel O, Najeeb RH, Greenberger S, Lee YN, Simon AJ, Lev A, Ma CA, Sun G, Blackstone SA, Milner JD, Somech R, Stauber T
J Clin Immunol 2019 May;39(4):401-413. Epub 2019 Apr 29 doi: 10.1007/s10875-019-00629-0. PMID: 31037583
Turvey SE, Durandy A, Fischer A, Fung SY, Geha RS, Gewies A, Giese T, Greil J, Keller B, McKinnon ML, Neven B, Rozmus J, Ruland J, Snow AL, Stepensky P, Warnatz K
J Allergy Clin Immunol 2014 Aug;134(2):276-84. doi: 10.1016/j.jaci.2014.06.015. PMID: 25087226Free PMC Article
Chinen J, Notarangelo LD, Shearer WT
J Allergy Clin Immunol 2014 Apr;133(4):967-76. Epub 2014 Feb 28 doi: 10.1016/j.jaci.2014.01.026. PMID: 24589342Free PMC Article

Clinical prediction guides

Sefer AP, Abolhassani H, Ober F, Kayaoglu B, Bilgic Eltan S, Kara A, Erman B, Surucu Yilmaz N, Aydogmus C, Aydemir S, Charbonnier LM, Kolukisa B, Azizi G, Delavari S, Momen T, Aliyeva S, Kendir Demirkol Y, Tekin S, Kiykim A, Baser OF, Cokugras H, Gursel M, Karakoc-Aydiner E, Ozen A, Krappmann D, Chatila TA, Rezaei N, Baris S
J Clin Immunol 2022 Apr;42(3):634-652. Epub 2022 Jan 26 doi: 10.1007/s10875-021-01191-4. PMID: 35079916
Punwani D, Wang H, Chan AY, Cowan MJ, Mallott J, Sunderam U, Mollenauer M, Srinivasan R, Brenner SE, Mulder A, Claas FH, Weiss A, Puck JM
J Clin Immunol 2015 Feb;35(2):135-46. Epub 2015 Jan 28 doi: 10.1007/s10875-014-0125-1. PMID: 25627829Free PMC Article
Chinen J, Notarangelo LD, Shearer WT
J Allergy Clin Immunol 2014 Apr;133(4):967-76. Epub 2014 Feb 28 doi: 10.1016/j.jaci.2014.01.026. PMID: 24589342Free PMC Article

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