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Immunodeficiency 78 with autoimmunity and developmental delay(IMD78)

MedGen UID:
1785772
Concept ID:
C5543159
Disease or Syndrome
Synonyms: IMD78; IMMUNODEFICIENCY 78 WITH AUTOIMMUNITY AND DEVELOPMENTAL DELAY; TPP2 DEFICIENCY
SNOMED CT: Tripeptidyl-peptidase II deficiency (1222681008); TRIANGLE (TPPII-related immunodeficiency, autoimmunity, neurodevelopmental delay, impaired glycolysis, lysosomal expansion) disease (1222681008); TPPII-related immunodeficiency, autoimmunity and neurodevelopmental delay with impaired glycolysis and lysosomal expansion disease (1222681008); TPPII (tripeptidyl-peptidase II) deficiency (1222681008); Autoimmune hemolytic anemia, autoimmune thrombocytopenia, primary immunodeficiency syndrome (1222681008); Evans syndrome associated with primary immunodeficiency (1222681008)
 
Gene (location): TPP2 (13q33.1)
 
Monarch Initiative: MONDO:0030971
OMIM®: 619220

Definition

Immunodeficiency-78 with autoimmunity and developmental delay (IMD78) is an autosomal recessive systemic disorder characterized by onset of symptoms in early childhood. Affected individuals present with features of immune deficiency, such as recurrent sinopulmonary or skin infections, as well as autoimmunity, including autoimmune cytopenias, hemolytic anemia, and thrombocytopenia. Autoimmune hepatitis or thyroid disease and central nervous system vasculitis with stroke may also occur. There is increased susceptibility to bacterial, viral, and fungal infections. Laboratory studies show lymphopenia with advanced differentiation and premature senescence of CD8+ T cells and B cells; some patients may have hypergammaglobulinemia. The findings indicate immune dysregulation. Patients also have global developmental delay with speech delay and variable intellectual disability. Many patients die prematurely, but successful hematopoietic bone marrow transplant may be curative (summary by Lu et al., 2014 and Atallah et al., 2021). [from OMIM]

Clinical features

From HPO
Facial papilloma
MedGen UID:
575740
Concept ID:
C0343643
Disease or Syndrome
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.
Mild global developmental delay
MedGen UID:
861405
Concept ID:
C4012968
Finding
A mild delay in the achievement of motor or mental milestones in the domains of development of a child.
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.
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.
Autoimmune hemolytic anemia
MedGen UID:
1918
Concept ID:
C0002880
Disease or Syndrome
An autoimmune form of hemolytic anemia.
Autoimmune thrombocytopenia
MedGen UID:
116621
Concept ID:
C0242584
Disease or Syndrome
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
Neutropenia in presence of anti-neutropil antibodies
MedGen UID:
137947
Concept ID:
C0340971
Disease or Syndrome
A type of neutropenia that is observed in the presence of granulocyte-specific antibodies.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargement (swelling) of a lymph node.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Recurrent oral herpes
MedGen UID:
697662
Concept ID:
C1274321
Disease or Syndrome
Recurrent episodes of oral herpes, typically characterized by blisters or ulcers on the gums, lips and/or tongue caused by herpes virus.
Fluctuating splenomegaly
MedGen UID:
322770
Concept ID:
C1835882
Finding
Intermittently increased size of the spleen.
Increased circulating IgM level
MedGen UID:
333454
Concept ID:
C1839972
Finding
An abnormally increased level of immunoglobulin M in blood.
Increased circulating IgG concentration
MedGen UID:
347032
Concept ID:
C1858977
Finding
An abnormally increased level of immunoglobulin G in blood.
Persistent CMV viremia
MedGen UID:
1696514
Concept ID:
C5139221
Finding
Lasting (uncontrolled) presence of cytomegalovirus in the blood circulation.

Recent clinical studies

Etiology

Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, Marks JB, Moore W, Moran A, Rodriguez H, Russell WE, Schatz D, Skyler JS, Tsalikian E, Wherrett DK, Ziegler AG, Greenbaum CJ; Type 1 Diabetes TrialNet Study Group
N Engl J Med 2019 Aug 15;381(7):603-613. Epub 2019 Jun 9 doi: 10.1056/NEJMoa1902226. PMID: 31180194Free PMC Article

Diagnosis

Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, Marks JB, Moore W, Moran A, Rodriguez H, Russell WE, Schatz D, Skyler JS, Tsalikian E, Wherrett DK, Ziegler AG, Greenbaum CJ; Type 1 Diabetes TrialNet Study Group
N Engl J Med 2019 Aug 15;381(7):603-613. Epub 2019 Jun 9 doi: 10.1056/NEJMoa1902226. PMID: 31180194Free PMC Article

Therapy

Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, Marks JB, Moore W, Moran A, Rodriguez H, Russell WE, Schatz D, Skyler JS, Tsalikian E, Wherrett DK, Ziegler AG, Greenbaum CJ; Type 1 Diabetes TrialNet Study Group
N Engl J Med 2019 Aug 15;381(7):603-613. Epub 2019 Jun 9 doi: 10.1056/NEJMoa1902226. PMID: 31180194Free PMC Article

Prognosis

Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, Marks JB, Moore W, Moran A, Rodriguez H, Russell WE, Schatz D, Skyler JS, Tsalikian E, Wherrett DK, Ziegler AG, Greenbaum CJ; Type 1 Diabetes TrialNet Study Group
N Engl J Med 2019 Aug 15;381(7):603-613. Epub 2019 Jun 9 doi: 10.1056/NEJMoa1902226. PMID: 31180194Free PMC Article

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