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Immunodeficiency 23(IMD23)

MedGen UID:
862808
Concept ID:
C4014371
Disease or Syndrome
Synonyms: IMD23; IMMUNODEFICIENCY WITH HYPER IgE AND COGNITIVE IMPAIRMENT; IMMUNODEFICIENCY-VASCULITIS-MYOCLONUS SYNDROME
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, 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).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
 
Gene (location): PGM3 (6q14.1)
OMIM®: 615816
Orphanet: ORPHA443811

Definition

IMD23 is an autosomal recessive primary immunodeficiency syndrome characterized by recurrent respiratory and skin infections beginning in early childhood. Laboratory studies are notable for increased serum IgE. Affected individuals also show developmental delay or cognitive impairment of varying severity (summary by Zhang et al., 2014). [from OMIM]

Additional description

From GHR
PGM3-congenital disorder of glycosylation (PGM3-CDG) is an inherited condition that primarily affects the immune system but can also involve other areas of the body. The pattern and severity of this disorder's signs and symptoms typically vary.Most people with PGM3-CDG have impaired immune function (immune deficiency). Many have a shortage of white blood cells (leukopenia), which normally protect the body from infection. Because affected individuals lack the necessary immune cells to fight off certain bacteria, viruses, and fungi, they are prone to repeated and persistent infections that often occur in the lungs, ears, skin, or gastrointestinal tract. In severe cases of PGM3-CDG, impaired bone marrow function may lead to a decrease in the production of all blood cells, resulting in a condition called bone marrow failure. Affected individuals usually also have allergies, asthma, or an inflammatory skin condition called eczema. People with PGM3-CDG may develop autoimmunity, which occurs when the body attacks its own tissues and organs by mistake. Persistent illness may cause affected children to grow more slowly than other individuals.Additionally, people with PGM3-CDG often have abnormally high levels of immune system proteins called antibodies (also known as immunoglobulins), particularly immunoglobulin E (IgE). Antibodies help protect the body against infection by attaching to specific foreign particles and germs, marking them for destruction. The effect of abnormal levels of antibodies in PGM3-CDG is unclear.People with PGM3-CDG often have intellectual disability, delayed development, and weak muscle tone (hypotonia). Many affected individuals have skeletal abnormalities involving the ribs or bones in the hands, feet, or spine. Some people with this condition have distinct facial features, such as a flat or sunken appearance of the middle of the face (midface hypoplasia), small chin (micrognathia), full lips, downturned corners of the mouth, and wide nostrils that open to the front rather than downward. PGM3-CDG can also cause problems in the lungs, gastrointestinal tract, and kidneys.Lifespan varies widely in people with PGM3-CDG; some do not survive past infancy while others live into late adulthood.  https://ghr.nlm.nih.gov/condition/pgm3-congenital-disorder-of-glycosylation

Clinical features

From HPO
Mesangiocapillary glomerulonephritis
MedGen UID:
9033
Concept ID:
C0017662
Disease or Syndrome
Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.
Erythema
MedGen UID:
11999
Concept ID:
C0041834
Disease or Syndrome
Red discoloration of the skin caused by infectious agents, inflammation, drug hypersensitivity, or underlying disease.
Vasculitis in the skin
MedGen UID:
488809
Concept ID:
C0262988
Disease or Syndrome
Inflammation of the blood vessel wall characterized by palpable purpura.
Conductive hearing impairment
MedGen UID:
9163
Concept ID:
C0018777
Disease or Syndrome
An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.
Sensorineural hearing loss
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from CRANIAL NERVE DISEASES; NEUROMUSCULAR DISEASES; CEREBELLAR DISEASES; BASAL GANGLIA DISEASES; BRAIN STEM diseases; or diseases of the corticobulbar tracts (see PYRAMIDAL TRACTS). The cortical language centers are intact in this condition. (From Adams et al., Principles of Neurology, 6th ed, p489)
Sensory impairment
MedGen UID:
6974
Concept ID:
C0020580
Finding
Absent or reduced sensitivity to cutaneous stimulation.
Cognitive impairment
MedGen UID:
90932
Concept ID:
C0338656
Mental or Behavioral Dysfunction
A notable change in cognitive function.
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.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Cortical myoclonus
MedGen UID:
785503
Concept ID:
C3698239
Disease or Syndrome
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
A decrease in the number of neutrophils in the peripheral blood.
Asthma
MedGen UID:
2109
Concept ID:
C0004096
Disease or Syndrome
A chronic respiratory disease manifested as difficulty breathing due to the narrowing of bronchial passageways.
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 respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Asthma
MedGen UID:
2109
Concept ID:
C0004096
Disease or Syndrome
A chronic respiratory disease manifested as difficulty breathing due to the narrowing of bronchial passageways.
Eczematous rash
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
A form of dermatitis characterized by red, itchy, scaly, or crusty patches that can be chronic or intermittent.
Mesangiocapillary glomerulonephritis
MedGen UID:
9033
Concept ID:
C0017662
Disease or Syndrome
Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.
Immunodeficiency
MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
A decrease in the number of neutrophils in the peripheral blood.
Allergic rhinitis
MedGen UID:
382012
Concept ID:
C2607914
Disease or Syndrome
An inflammation of the NASAL MUCOSA triggered by ALLERGENS.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
A congenital or acquired spinal deformity characterized by lateral curvature of the spine.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Allergic rhinitis
MedGen UID:
382012
Concept ID:
C2607914
Disease or Syndrome
An inflammation of the NASAL MUCOSA triggered by ALLERGENS.
Eczematous rash
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
A form of dermatitis characterized by red, itchy, scaly, or crusty patches that can be chronic or intermittent.
Erythema
MedGen UID:
11999
Concept ID:
C0041834
Disease or Syndrome
Red discoloration of the skin caused by infectious agents, inflammation, drug hypersensitivity, or underlying disease.
Vasculitis in the skin
MedGen UID:
488809
Concept ID:
C0262988
Disease or Syndrome
Inflammation of the blood vessel wall characterized by palpable purpura.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVImmunodeficiency 23

Recent clinical studies

Etiology

Janssen LMA, Macken T, Creemers MCW, Pruijt JFM, Eijk JJJ, de Vries E
Clin Exp Immunol 2018 Feb;191(2):203-211. Epub 2017 Oct 27 doi: 10.1111/cei.13065. PMID: 28984901Free PMC Article
Mohanty MC, Madkaikar MR, Desai M, Taur P, Nalavade UP, Sharma DK, Gupta M, Dalvi A, Shabrish S, Kulkarni M, Aluri J, Deshpande JM
Emerg Infect Dis 2017 Oct;23(10):1664-1670. doi: 10.3201/eid2310.170724. PMID: 28930011Free PMC Article
Azizi G, Abolhassani H, Mahdaviani SA, Chavoshzadeh Z, Eshghi P, Yazdani R, Kiaee F, Shaghaghi M, Mohammadi J, Rezaei N, Hammarström L, Aghamohammadi A
Pediatr Allergy Immunol 2017 Aug;28(5):478-484. Epub 2017 Jun 19 doi: 10.1111/pai.12735. PMID: 28512785
Hajjar J, Guffey D, Minard CG, Orange JS
J Clin Immunol 2017 Feb;37(2):153-165. Epub 2017 Jan 26 doi: 10.1007/s10875-016-0367-1. PMID: 28124237Free PMC Article
Nabavi M, Arshi S, Bemanian MH, Aghamohammadi A, Mansouri D, Hedayat M, Nateghian A, Noorbakhsh S, Ehsanipour F, Faranoush M, Shakeri R, Mesdaghi M, Taghvaei B, Ghalebaghi B, Babaie D, Bahrami A, Fallahpour M, Esmaeilzadeh H, Ali Hamidieh A, Rekabi M, Ahmadian J, Eslami N, Shokri S, Afshar M, Jalali F, Akbarpour N, Molatefi R, Rezaei N
Allergol Immunopathol (Madr) 2016 Jul-Aug;44(4):322-30. Epub 2016 Jan 20 doi: 10.1016/j.aller.2015.09.006. PMID: 26803694

Diagnosis

Al-Herz W, Massaad MJ, Chou J, Notarangelo LD, Geha RS
Clin Immunol 2018 Feb;187:68-75. Epub 2017 Oct 16 doi: 10.1016/j.clim.2017.10.006. PMID: 29051008Free PMC Article
Bausch-Jurken MT, Verbsky JW, Gonzaga KA, Elms NP, Hintermeyer MK, Gauld SB, Routes JM
J Clin Immunol 2017 Jul;37(5):427-433. Epub 2017 Jun 7 doi: 10.1007/s10875-017-0406-6. PMID: 28589420
Azizi G, Abolhassani H, Mahdaviani SA, Chavoshzadeh Z, Eshghi P, Yazdani R, Kiaee F, Shaghaghi M, Mohammadi J, Rezaei N, Hammarström L, Aghamohammadi A
Pediatr Allergy Immunol 2017 Aug;28(5):478-484. Epub 2017 Jun 19 doi: 10.1111/pai.12735. PMID: 28512785
Hajjar J, Guffey D, Minard CG, Orange JS
J Clin Immunol 2017 Feb;37(2):153-165. Epub 2017 Jan 26 doi: 10.1007/s10875-016-0367-1. PMID: 28124237Free PMC Article
Peacock ME, Arce RM, Cutler CW
Oral Dis 2017 Oct;23(7):866-888. Epub 2016 Oct 10 doi: 10.1111/odi.12584. PMID: 27630012Free PMC Article

Therapy

Al-Herz W, Massaad MJ, Chou J, Notarangelo LD, Geha RS
Clin Immunol 2018 Feb;187:68-75. Epub 2017 Oct 16 doi: 10.1016/j.clim.2017.10.006. PMID: 29051008Free PMC Article
Mohanty MC, Madkaikar MR, Desai M, Taur P, Nalavade UP, Sharma DK, Gupta M, Dalvi A, Shabrish S, Kulkarni M, Aluri J, Deshpande JM
Emerg Infect Dis 2017 Oct;23(10):1664-1670. doi: 10.3201/eid2310.170724. PMID: 28930011Free PMC Article
Bausch-Jurken MT, Verbsky JW, Gonzaga KA, Elms NP, Hintermeyer MK, Gauld SB, Routes JM
J Clin Immunol 2017 Jul;37(5):427-433. Epub 2017 Jun 7 doi: 10.1007/s10875-017-0406-6. PMID: 28589420
van de Vosse E, van Ostaijen-Ten Dam MM, Vermaire R, Verhard EM, Waaijer JL, Bakker JA, Bernards ST, Eibel H, van Tol MJ, van Dissel JT, Haverkamp MH
Clin Immunol 2017 Jul;180:111-119. Epub 2017 May 6 doi: 10.1016/j.clim.2017.05.008. PMID: 28487087
Nabavi M, Arshi S, Bemanian MH, Aghamohammadi A, Mansouri D, Hedayat M, Nateghian A, Noorbakhsh S, Ehsanipour F, Faranoush M, Shakeri R, Mesdaghi M, Taghvaei B, Ghalebaghi B, Babaie D, Bahrami A, Fallahpour M, Esmaeilzadeh H, Ali Hamidieh A, Rekabi M, Ahmadian J, Eslami N, Shokri S, Afshar M, Jalali F, Akbarpour N, Molatefi R, Rezaei N
Allergol Immunopathol (Madr) 2016 Jul-Aug;44(4):322-30. Epub 2016 Jan 20 doi: 10.1016/j.aller.2015.09.006. PMID: 26803694

Prognosis

Shah NN, Freeman AF, Su H, Cole K, Parta M, Moutsopoulos NM, Baris S, Karakoc-Aydiner E, Hughes TE, Kong HH, Holland SM, Hickstein DD
Biol Blood Marrow Transplant 2017 Jun;23(6):980-990. Epub 2017 Mar 10 doi: 10.1016/j.bbmt.2017.03.016. PMID: 28288951Free PMC Article
Hajjar J, Guffey D, Minard CG, Orange JS
J Clin Immunol 2017 Feb;37(2):153-165. Epub 2017 Jan 26 doi: 10.1007/s10875-016-0367-1. PMID: 28124237Free PMC Article
Nabavi M, Arshi S, Bemanian MH, Aghamohammadi A, Mansouri D, Hedayat M, Nateghian A, Noorbakhsh S, Ehsanipour F, Faranoush M, Shakeri R, Mesdaghi M, Taghvaei B, Ghalebaghi B, Babaie D, Bahrami A, Fallahpour M, Esmaeilzadeh H, Ali Hamidieh A, Rekabi M, Ahmadian J, Eslami N, Shokri S, Afshar M, Jalali F, Akbarpour N, Molatefi R, Rezaei N
Allergol Immunopathol (Madr) 2016 Jul-Aug;44(4):322-30. Epub 2016 Jan 20 doi: 10.1016/j.aller.2015.09.006. PMID: 26803694
Janssen WJ, Nierkens S, Sanders EA, Boes M, van Montfrans JM
Vaccine 2015 Nov 17;33(46):6320-6. Epub 2015 Sep 28 doi: 10.1016/j.vaccine.2015.09.041. PMID: 26413880
Kashani S, Carr TF, Grammer LC, Schleimer RP, Hulse KE, Kato A, Kern RC, Conley DB, Chandra RK, Tan BK, Peters AT
J Allergy Clin Immunol Pract 2015 Mar-Apr;3(2):236-42. Epub 2014 Nov 25 doi: 10.1016/j.jaip.2014.09.022. PMID: 25609325Free PMC Article

Clinical prediction guides

Benbrahim O, Viallard JF, Choquet S, Royer B, Bauduer F, Decaux O, Crave JC, Fardini Y, Clerson P, Lévy V
Eur J Haematol 2018 Jul;101(1):48-56. Epub 2018 May 17 doi: 10.1111/ejh.13078. PMID: 29644723
Azizi G, Abolhassani H, Mahdaviani SA, Chavoshzadeh Z, Eshghi P, Yazdani R, Kiaee F, Shaghaghi M, Mohammadi J, Rezaei N, Hammarström L, Aghamohammadi A
Pediatr Allergy Immunol 2017 Aug;28(5):478-484. Epub 2017 Jun 19 doi: 10.1111/pai.12735. PMID: 28512785
Kearns S, Kristofek L, Bolgar W, Seidu L, Kile S
J Manag Care Spec Pharm 2017 Apr;23(4):400-406. doi: 10.18553/jmcp.2017.23.4.400. PMID: 28345437
Janssen WJ, Nierkens S, Sanders EA, Boes M, van Montfrans JM
Vaccine 2015 Nov 17;33(46):6320-6. Epub 2015 Sep 28 doi: 10.1016/j.vaccine.2015.09.041. PMID: 26413880
Zeng H, Tao Y, Chen X, Zeng P, Wang B, Wei R, Yao C, Xie Y, Li F, Tang Y, Cui Y, Sun G
J Investig Allergol Clin Immunol 2013;23(5):302-8. PMID: 24260974

Recent systematic reviews

Pormohammad A, Nasiri MJ, Riahi SM, Fallah F
Trop Med Int Health 2018 Jun;23(6):589-595. Epub 2018 May 21 doi: 10.1111/tmi.13059. PMID: 29660820
Abdallah A, Chang JL, O'Carroll CB, Musubire A, Chow FC, Wilson AL, Siedner MJ
J Stroke Cerebrovasc Dis 2018 Jul;27(7):1828-1836. Epub 2018 Apr 5 doi: 10.1016/j.jstrokecerebrovasdis.2018.02.016. PMID: 29628338Free PMC Article
Naik AN, Clinkscales WB, Kato MG, Nguyen SA, Gillespie MB
Head Neck 2018 May;40(5):1073-1081. Epub 2018 Jan 12 doi: 10.1002/hed.25046. PMID: 29327783
Gili S, Grosso Marra W, D'Ascenzo F, Lonni E, Calcagno A, Cannillo M, Ballocca F, Cerrato E, Pianelli M, Barbero U, Mancone M, DiNicolantonio JJ, Lavie CJ, Omedè P, Montefusco A, Bonora S, Gasparini M, Biondi-Zoccai G, Moretti C, Gaita F
Eur Heart J 2016 Dec 21;37(48):3600-3609. Epub 2016 Feb 6 doi: 10.1093/eurheartj/ehv734. PMID: 26851703
Bhatia K, Shiels MS, Berg A, Engels EA
Curr Opin Oncol 2012 Sep;24(5):537-46. doi: 10.1097/CCO.0b013e328355e115. PMID: 22729152Free PMC Article

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