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Inflammatory bowel disease, immunodeficiency, and encephalopathy(IBDIMDE)

MedGen UID:
1648434
Concept ID:
C4748708
Disease or Syndrome
Synonyms: IBDIMDE; INFLAMMATORY BOWEL DISEASE, IMMUNODEFICIENCY, AND ENCEPHALOPATHY
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): TGFB1 (19q13.2)
 
Monarch Initiative: MONDO:0032601
OMIM®: 618213
Orphanet: ORPHA565788

Definition

A rare genetic disease characterized by infantile onset of severe inflammatory bowel disease manifesting with bloody diarrhea and failure to thrive, and central nervous system disease with global developmental delay and regression, impaired speech, hypotonia, hyperreflexia, and epilepsy. Brain imaging shows global cerebral atrophy, thin corpus callosum, delayed myelination, and posterior leukoencephalopathy. Cases with recurrent infections and impaired T-cell responses to stimulation, as well as decreased T-cell subsets, have been reported. [from ORDO]

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.
Perianal abscess
MedGen UID:
14677
Concept ID:
C0031019
Disease or Syndrome
The presence of an abscess located around the anus.
Bloody diarrhea
MedGen UID:
56232
Concept ID:
C0151594
Disease or Syndrome
Passage of many stools containing blood.
Pancolitis
MedGen UID:
1720692
Concept ID:
C0868908
Disease or Syndrome
Inflammation of the entire colon.
Anoperineal fistula
MedGen UID:
324365
Concept ID:
C1835798
Anatomical Abnormality
The presence of a fistula (abnormal tunnel) between the anal canal and the perineum.
Eosinophilic infiltration of the esophagus
MedGen UID:
1637185
Concept ID:
C4703646
Finding
Infiltration of numerous eosinophils (usually greater than 15 per high power field) into the squamous epithelium of the esophagus, and layering of eosinophils on the surface layer of the esophagus.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Focal impaired awareness seizure
MedGen UID:
543022
Concept ID:
C0270834
Disease or Syndrome
Focal impaired awareness seizure (or focal seizure with impaired or lost awareness) is a type of focal-onset seizure characterized by some degree (which may be partial) of impairment of the person's awareness of themselves or their surroundings at any point during the seizure.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
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.
Hypsarrhythmia
MedGen UID:
195766
Concept ID:
C0684276
Finding
Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG).
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
Myoclonic seizure
MedGen UID:
1385980
Concept ID:
C4317123
Sign or Symptom
A myoclonic seizure is a type of motor seizure characterised by sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.
Hypochromic anemia
MedGen UID:
8065
Concept ID:
C0002884
Disease or Syndrome
A type of anemia characterized by an abnormally low concentration of hemoglobin in the erythrocytes.
Thrombocytosis
MedGen UID:
163397
Concept ID:
C0836924
Disease or Syndrome
Increased numbers of platelets in the peripheral blood.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
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.
Leukocytosis
MedGen UID:
9736
Concept ID:
C0023518
Disease or Syndrome
An abnormal increase in the number of leukocytes in the blood.
Increased circulating IgE level
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.
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.
Decreased T cell activation
MedGen UID:
339550
Concept ID:
C1846550
Finding
Decreased or impaired activation of T cells in response to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific.
Increased circulating IgG level
MedGen UID:
347032
Concept ID:
C1858977
Finding
An abnormally increased level of immunoglobulin G in blood.
Defective T cell proliferation
MedGen UID:
868165
Concept ID:
C4022557
Cell or Molecular Dysfunction
A reduced ability of a T cell population to expand by cell division following T cell activation.
Severe varicella zoster infection
MedGen UID:
1688785
Concept ID:
C5139168
Disease or Syndrome
An unusually severe form of varicella zoster virus (VZV) infection. In the majority of the cases, especially in children, varicella is a very mild infection characterised by skin lesions, low grade fever and malaise. Severe infection is characterized by manifestions including VZV pneumonia, hepatitis, meningitis, and disseminated varicella.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVInflammatory bowel disease, immunodeficiency, and encephalopathy

Professional guidelines

PubMed

Kinlen LJ
Am J Med 1985 Jan 21;78(1A):44-9. doi: 10.1016/0002-9343(85)90245-1. PMID: 3970040

Recent clinical studies

Etiology

Dafsari HS, Pemberton JG, Ferrer EA, Yammine T, Farra C, Mohammadi MH, Ghayoor Karimiani E, Hashemi N, Souaid M, Sabbagh S, Najarzadeh Torbati P, Khan S, Roze E, Moreno-De-Luca A, Bertoli-Avella AM, Houlden H, Balla T, Maroofian R
Ann Clin Transl Neurol 2022 Sep;9(9):1345-1358. Epub 2022 Jul 25 doi: 10.1002/acn3.51634. PMID: 35880319Free PMC Article
Salter CG, Cai Y, Lo B, Helman G, Taylor H, McCartney A, Leslie JS, Accogli A, Zara F, Traverso M, Fasham J, Lees JA, Ferla MP, Chioza BA, Wenger O, Scott E, Cross HE, Crawford J, Warshawsky I, Keisling M, Agamanolis D, Ward Melver C, Cox H, Elawad M, Marton T, Wakeling MN, Holzinger D, Tippelt S, Munteanu M, Valcheva D, Deal C, Van Meerbeke S, Walsh Vockley C, Butte MJ, Acar U, van der Knaap MS, Korenke GC, Kotzaeridou U, Balla T, Simons C, Uhlig HH, Crosby AH, De Camilli P, Wolf NI, Baple EL
Brain 2021 Dec 31;144(12):3597-3610. doi: 10.1093/brain/awab313. PMID: 34415310Free PMC Article
Palacios Argueta P, Salazar M, Attar B, Simons-Linares R, Shen B
Inflamm Bowel Dis 2021 Mar 15;27(4):530-537. doi: 10.1093/ibd/izaa224. PMID: 32812037
Fragoulis GE, McInnes IB, Siebert S
Rheumatology (Oxford) 2019 Feb 1;58(Suppl 1):i43-i54. doi: 10.1093/rheumatology/key276. PMID: 30806709Free PMC Article
Bornstein MM, Cionca N, Mombelli A
Int J Oral Maxillofac Implants 2009;24 Suppl:12-27. PMID: 19885432

Diagnosis

Serra EG, Schwerd T, Moutsianas L, Cavounidis A, Fachal L, Pandey S, Kammermeier J, Croft NM, Posovszky C, Rodrigues A, Russell RK, Barakat F, Auth MKH, Heuschkel R, Zilbauer M, Fyderek K, Braegger C, Travis SP, Satsangi J, Parkes M, Thapar N, Ferry H, Matte JC, Gilmour KC, Wedrychowicz A, Sullivan P, Moore C, Sambrook J, Ouwehand W, Roberts D, Danesh J, Baeumler TA, Fulga TA, Carrami EM, Ahmed A, Wilson R, Barrett JC, Elkadri A, Griffiths AM; COLORS in IBD group investigators; Oxford IBD cohort study investigators; INTERVAL Study; Swiss IBD cohort investigators; UK IBD Genetics Consortium; NIDDK IBD Genetics Consortium, Snapper SB, Shah N, Muise AM, Wilson DC, Uhlig HH, Anderson CA
Nat Commun 2020 Feb 21;11(1):995. doi: 10.1038/s41467-019-14275-y. PMID: 32081864Free PMC Article
Lee WI, Huang JL, Chen CC, Lin JL, Wu RC, Jaing TH, Ou LS
Medicine (Baltimore) 2016 Mar;95(9):e2918. doi: 10.1097/MD.0000000000002918. PMID: 26945392Free PMC Article
Berody S, Galeotti C, Koné-Paut I, Piram M
Joint Bone Spine 2015 Jul;82(4):240-4. Epub 2015 Feb 9 doi: 10.1016/j.jbspin.2014.12.011. PMID: 25677409
Bharat A, Xie F, Baddley JW, Beukelman T, Chen L, Calabrese L, Delzell E, Grijalva CG, Patkar NM, Saag K, Winthrop KL, Curtis JR
Arthritis Care Res (Hoboken) 2012 Apr;64(4):612-5. doi: 10.1002/acr.21564. PMID: 22162369Free PMC Article
Bornstein MM, Cionca N, Mombelli A
Int J Oral Maxillofac Implants 2009;24 Suppl:12-27. PMID: 19885432

Therapy

Fragoulis GE, McInnes IB, Siebert S
Rheumatology (Oxford) 2019 Feb 1;58(Suppl 1):i43-i54. doi: 10.1093/rheumatology/key276. PMID: 30806709Free PMC Article
Thomas LV, Suzuki K, Zhao J
Br J Nutr 2015 Dec;114 Suppl 1:S1-15. doi: 10.1017/S0007114515004043. PMID: 26548336
Connors W, Griffiths C, Patel J, Belletrutti PJ
BMC Gastroenterol 2014 Jul 14;14:127. doi: 10.1186/1471-230X-14-127. PMID: 25022612Free PMC Article
Garrido-Mesa N, Zarzuelo A, Gálvez J
Br J Pharmacol 2013 May;169(2):337-52. doi: 10.1111/bph.12139. PMID: 23441623Free PMC Article
Bornstein MM, Cionca N, Mombelli A
Int J Oral Maxillofac Implants 2009;24 Suppl:12-27. PMID: 19885432

Prognosis

Palacios Argueta P, Salazar M, Attar B, Simons-Linares R, Shen B
Inflamm Bowel Dis 2021 Mar 15;27(4):530-537. doi: 10.1093/ibd/izaa224. PMID: 32812037
Schaff LR, Marghoob A, Rosenblum MK, Meyer R, Khakoo Y
Pediatr Dermatol 2019 Jul;36(4):497-500. Epub 2019 Mar 13 doi: 10.1111/pde.13804. PMID: 30868657Free PMC Article
Berody S, Galeotti C, Koné-Paut I, Piram M
Joint Bone Spine 2015 Jul;82(4):240-4. Epub 2015 Feb 9 doi: 10.1016/j.jbspin.2014.12.011. PMID: 25677409
Connors W, Griffiths C, Patel J, Belletrutti PJ
BMC Gastroenterol 2014 Jul 14;14:127. doi: 10.1186/1471-230X-14-127. PMID: 25022612Free PMC Article
Bharat A, Xie F, Baddley JW, Beukelman T, Chen L, Calabrese L, Delzell E, Grijalva CG, Patkar NM, Saag K, Winthrop KL, Curtis JR
Arthritis Care Res (Hoboken) 2012 Apr;64(4):612-5. doi: 10.1002/acr.21564. PMID: 22162369Free PMC Article

Clinical prediction guides

Dafsari HS, Pemberton JG, Ferrer EA, Yammine T, Farra C, Mohammadi MH, Ghayoor Karimiani E, Hashemi N, Souaid M, Sabbagh S, Najarzadeh Torbati P, Khan S, Roze E, Moreno-De-Luca A, Bertoli-Avella AM, Houlden H, Balla T, Maroofian R
Ann Clin Transl Neurol 2022 Sep;9(9):1345-1358. Epub 2022 Jul 25 doi: 10.1002/acn3.51634. PMID: 35880319Free PMC Article
Palacios Argueta P, Salazar M, Attar B, Simons-Linares R, Shen B
Inflamm Bowel Dis 2021 Mar 15;27(4):530-537. doi: 10.1093/ibd/izaa224. PMID: 32812037
Serra EG, Schwerd T, Moutsianas L, Cavounidis A, Fachal L, Pandey S, Kammermeier J, Croft NM, Posovszky C, Rodrigues A, Russell RK, Barakat F, Auth MKH, Heuschkel R, Zilbauer M, Fyderek K, Braegger C, Travis SP, Satsangi J, Parkes M, Thapar N, Ferry H, Matte JC, Gilmour KC, Wedrychowicz A, Sullivan P, Moore C, Sambrook J, Ouwehand W, Roberts D, Danesh J, Baeumler TA, Fulga TA, Carrami EM, Ahmed A, Wilson R, Barrett JC, Elkadri A, Griffiths AM; COLORS in IBD group investigators; Oxford IBD cohort study investigators; INTERVAL Study; Swiss IBD cohort investigators; UK IBD Genetics Consortium; NIDDK IBD Genetics Consortium, Snapper SB, Shah N, Muise AM, Wilson DC, Uhlig HH, Anderson CA
Nat Commun 2020 Feb 21;11(1):995. doi: 10.1038/s41467-019-14275-y. PMID: 32081864Free PMC Article
Marzolini C, Paus E, Buclin T, Kim RB
Clin Pharmacol Ther 2004 Jan;75(1):13-33. doi: 10.1016/j.clpt.2003.09.012. PMID: 14749689
Plata-Salamán CR
Nutrition 2000 Oct;16(10):1009-12. doi: 10.1016/s0899-9007(00)00413-5. PMID: 11054608

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