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Autoinflammatory-pancytopenia syndrome due to DNASE2 deficiency(AIPCS)

MedGen UID:
1803642
Concept ID:
C5676977
Disease or Syndrome
Synonym: Autoinflammatory-pancytopenia syndrome
 
Gene (location): DNASE2 (19p13.13)
 
Monarch Initiative: MONDO:0800132
OMIM®: 619858

Definition

Autoinflammatory-pancytopenia syndrome (AIPCS) is an autosomal recessive disorder characterized by severe anemia and thrombocytopenia apparent from early infancy, hepatosplenomegaly, and recurrent fevers associated with a hyperinflammatory state. Additional systemic features may include chronic diarrhea, proteinuria with renal disease, liver fibrosis with elevated liver enzymes, deforming arthropathy, and vasculitic skin lesions. Some patients may have motor delay or learning difficulties associated with subcortical white matter lesions on brain imaging. Laboratory studies show increased levels of proinflammatory cytokines and increased expression of interferon-stimulated genes (ISGs), consistent with a type I interferonopathy (Rodero et al., 2017). Treatment with a JAK (see 147795) inhibitor (baricitinib) may be effective (Hong et al., 2020). [from OMIM]

Clinical features

From HPO
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
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.
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
Hepatic fibrosis
MedGen UID:
116093
Concept ID:
C0239946
Disease or Syndrome
The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Cholestatic liver disease
MedGen UID:
163651
Concept ID:
C0860204
Disease or Syndrome
Intestinal inflammation
MedGen UID:
1778078
Concept ID:
C3889047
Pathologic Function
A reaction characterizeds by capillary dilatation, leukocytic infiltration, redness, heat, pain, swelling localized to the in the intestinal tract.
Delayed gross motor development
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Pancytopenia
MedGen UID:
18281
Concept ID:
C0030312
Disease or Syndrome
An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).
Arthropathy
MedGen UID:
7190
Concept ID:
C0022408
Disease or Syndrome
Any disorder of the joints.
Lipodystrophy
MedGen UID:
6111
Concept ID:
C0023787
Disease or Syndrome
Degenerative changes of the fat tissue.
Chilblains
MedGen UID:
886
Concept ID:
C0008058
Injury or Poisoning
Chilblains, also called perniosis, are an inflammatory skin condition related to an abnormal vascular response to the cold. We are unaware of a reliable estimate of incidence. It typically presents as tender, pruritic red or bluish lesions located symmetrically on the dorsal aspect of the fingers, toes, ears and nose. Less commonly, reports describe involvement of the thighs and buttocks. The lesions present hours after exposure to cold and usually resolve spontaneously in one to three weeks.
Mesangiocapillary glomerulonephritis
MedGen UID:
9033
Concept ID:
C0017662
Disease or Syndrome
A type of glomerulonephritis characterized by diffuse mesangial cell proliferation and the thickening of capillary walls due to subendothelial extension of the mesangium. The term membranoproliferative glomerulonephritis is often employed to denote a general pattern of glomerular injury seen in a variety of disease processes that share a common pathogenetic mechanism, rather than to describe a single disease entity
Granuloma
MedGen UID:
5376
Concept ID:
C0018188
Pathologic Function
A compact, organized collection of mature mononuclear phagocytes, which may be but is not necessarily accompanied by accessory features such as necrosis.
Hemophagocytosis
MedGen UID:
163750
Concept ID:
C0876991
Disease or Syndrome
Phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues.
Severe Epstein Barr virus infection
MedGen UID:
1635633
Concept ID:
C4703482
Disease or Syndrome
An unusually severe Epstein Barr virus (EBV) infection.
Diabetes mellitus type 1
MedGen UID:
41522
Concept ID:
C0011854
Disease or Syndrome
Type 1 diabetes mellitus (T1D), also designated insulin-dependent diabetes mellitus (IDDM), is a disorder of glucose homeostasis characterized by susceptibility to ketoacidosis in the absence of insulin therapy. It is a genetically heterogeneous autoimmune disease affecting about 0.3% of Caucasian populations (Todd, 1990). Genetic studies of T1D have focused on the identification of loci associated with increased susceptibility to this multifactorial phenotype. The classic phenotype of diabetes mellitus is polydipsia, polyphagia, and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.

Recent clinical studies

Diagnosis

Batlle-Masó L, Mensa-Vilaró A, Solís-Moruno M, Marquès-Bonet T, Arostegui JI, Casals F
Eur J Med Genet 2020 May;63(5):103920. Epub 2020 Mar 25 doi: 10.1016/j.ejmg.2020.103920. PMID: 32222431

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