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Proteasome-associated autoinflammatory syndrome 2(PRAAS2)

MedGen UID:
1648482
Concept ID:
C4747989
Disease or Syndrome
Synonyms: PRAAS2; PROTEASOME-ASSOCIATED AUTOINFLAMMATORY SYNDROME 2
 
Gene (location): POMP (13q12.3)
 
Monarch Initiative: MONDO:0054700
OMIM®: 618048

Definition

Proteasome-associated autoinflammatory syndrome-2 (PRAAS2) is an autosomal dominant disorder with onset in early infancy. Affected individuals develop severe inflammatory neutrophilic dermatitis, autoimmunity, and variable immunodeficiency (summary by Poli et al., 2018). For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040). [from OMIM]

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Clinodactyly
MedGen UID:
1644094
Concept ID:
C4551485
Congenital Abnormality
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
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.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Lipodystrophy
MedGen UID:
6111
Concept ID:
C0023787
Disease or Syndrome
Degenerative changes of the fat tissue.
Antinuclear antibody positivity
MedGen UID:
101792
Concept ID:
C0151480
Laboratory or Test Result
The presence of autoantibodies in the serum that react against nuclei or nuclear components.
Increased circulating IgA concentration
MedGen UID:
66800
Concept ID:
C0239984
Finding
An abnormally increased level of immunoglobulin A in blood.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargement (swelling) of a lymph node.
Increased CD4:CD8 ratio
MedGen UID:
1614673
Concept ID:
C0920173
Finding
An abnormal elevation of the relative proportion of CD4+ to CD8+ T cells.
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.
B lymphocytopenia
MedGen UID:
340780
Concept ID:
C1855067
Finding
An abnormal decrease from the normal count of B cells.
Increased circulating IgG concentration
MedGen UID:
347032
Concept ID:
C1858977
Finding
An abnormally increased level of immunoglobulin G in blood.
Decreased proportion of memory B cells
MedGen UID:
893145
Concept ID:
C4072913
Finding
A reduction in the normal proportion of memory B cells (CD19+/CD27+) in circulation relative to the total number of B cells. Memory B cells develop from naive B cells. Upon antigen rechallenge, memory B cells rapidly expand and differentiate into plasma cells under the cognate control of memory Th cells (Phase IV).
Anti-thyroid peroxidase antibody positivity
MedGen UID:
1392952
Concept ID:
C4476743
Laboratory or Test Result
The presence of autoantibodies (immunoglobulins) in the serum that react against thyroid peroxidase.
Neutrophilic infiltration of the skin
MedGen UID:
1620481
Concept ID:
C4531258
Anatomical Abnormality
A predominantly neutrophilic infiltrate of the dermis and or epidermis (i.e., a large number of neutrophils inferred to have migrated into the skin).
Anti-thyroglobulin antibody positivity
MedGen UID:
1670955
Concept ID:
C4732836
Finding
The presence of autoantibodies (immunoglobulins) in the serum that react to thyroglobulin.
Abnormal circulating IgM concentration
MedGen UID:
1688699
Concept ID:
C5139423
Finding
An abnormal deviation from normal levels of IgM immunoglobulin in blood.
Anti-beta-2-Glycoprotein I IgG antibody positivity
MedGen UID:
1814321
Concept ID:
C5676752
Laboratory or Test Result
Presence of IgG antibodies against beta 2 glycoprotein I in the circulation. Beta-2 glycoprotein I (beta2GPI) is the principal target of autoantibodies in the antiphospholipid syndrome.
Skin rash
MedGen UID:
1830322
Concept ID:
C5779628
Sign or Symptom
A red eruption of the skin.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Elevated erythrocyte sedimentation rate
MedGen UID:
57727
Concept ID:
C0151632
Finding
An increased erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen.
Elevated circulating C-reactive protein concentration
MedGen UID:
892906
Concept ID:
C4023452
Finding
An abnormal elevation of the C-reactive protein level in the blood circulation.
Periorbital edema
MedGen UID:
56223
Concept ID:
C0151205
Pathologic Function
Edema affecting the region situated around the orbit of the eye.
Subcutaneous nodule
MedGen UID:
101803
Concept ID:
C0151811
Pathologic Function
Slightly elevated lesions on or in the skin with a diameter of over 5 mm.
Annular cutaneous lesion
MedGen UID:
1391698
Concept ID:
C4476833
Finding
A lesion of the skin with a ring-like distribution.

Professional guidelines

PubMed

Cetin Gedik K, Ortega-Villa AM, Materne G, Rastegar A, Montealegre Sanchez GA, Reinhardt A, Brogan PA, Berkun Y, Murias S, Robles M, Schalm S, de Jesus AA, Goldbach-Mansky R
Ann Rheum Dis 2024 Aug 27;83(9):1181-1188. doi: 10.1136/ard-2023-225463. PMID: 38653530Free PMC Article
McDermott A, Jacks J, Kessler M, Emanuel PD, Gao L
Int J Dermatol 2015 Feb;54(2):121-9. Epub 2014 Dec 18 doi: 10.1111/ijd.12695. PMID: 25521013

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