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Lazy leukocyte syndrome(PFITS)

MedGen UID:
78795
Concept ID:
C0272174
Disease or Syndrome
Synonym: Lazy Leukocyte Syndrome
SNOMED CT: Lazy leukocyte syndrome (71436005); Periodic fever, immunodeficiency, thrombocytopenia syndrome (71436005)
 
Gene (location): WDR1 (4p16.1)
 
Monarch Initiative: MONDO:0007883
OMIM®: 150550

Definition

Periodic fever, immunodeficiency, and thrombocytopenia syndrome (PFITS) is an autosomal recessive immunologic disorder with variable manifestations. Common features include early-onset recurrent respiratory infections, stomatitis, and cutaneous infections. Organisms usually include bacteria such as pneumococcus, Staphylococcus, and H. influenzae, but severe viral infections, including varicella, may also occur. Laboratory investigations may show neutropenia, neutrophilia, leukocytosis, or lymphopenia, although levels of immune cells may also be normal. Detailed studies often show impaired neutrophil chemotaxis associated with increased or abnormal F-actin levels, and impaired, normal, or even increased oxidative burst, depending on the stimulus. B- and T-cell abnormalities have also been observed. Some patients develop autoimmune manifestations, including chronic thrombocytopenia, anemia, and periodic fevers, associated with activation of the inflammasome. Early death may occur; however, hematopoietic stem cell transplantation may be curative (summary by Kuhns et al., 2016, Standing et al., 2017, and Pfajfer et al., 2018). [from OMIM]

Clinical features

From HPO
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Specific learning disability
MedGen UID:
871302
Concept ID:
C4025790
Mental or Behavioral Dysfunction
Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence.
Intermittent thrombocytopenia
MedGen UID:
374151
Concept ID:
C1839167
Finding
Reduced platelet count that occurs sporadically, i.e., it comes and goes.
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 pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Abscess
MedGen UID:
1684
Concept ID:
C0000833
Disease or Syndrome
An abscess is a localized collection of purulent material surrounded by inflammation and granulation.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargement (swelling) of a lymph node.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
B lymphocytopenia
MedGen UID:
340780
Concept ID:
C1855067
Finding
An abnormal decrease from the normal count of B cells.
Chronic oral candidiasis
MedGen UID:
870166
Concept ID:
C4024599
Disease or Syndrome
Chronic accumulation and overgrowth of the fungus Candida albicans on the mucous membranes of the mouth, generally manifested as associated with creamy white lesions on the tongue or inner cheeks, occasionally spreading to the gums, tonsils, palate or oropharynx.
Abnormal CD4:CD8 ratio
MedGen UID:
1619994
Concept ID:
C4531154
Finding
Any abnormality in the relative amount of CD4+ and CD8+ T lymphocytes.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.
Recurrent aphthous stomatitis
MedGen UID:
445425
Concept ID:
C2937365
Disease or Syndrome
Recurrent episodes of ulceration of the oral mucosa, typically presenting as painful, sharply circumscribed fibrin-covered mucosal defects with a hyperemic border.
Pyoderma gangrenosum
MedGen UID:
43224
Concept ID:
C0085652
Disease or Syndrome
A deep skin ulcer with a well defined border, which is usually violet or blue. The ulcer edge is often undermined (worn and damaged) and the surrounding skin is erythematous and indurated. The ulcer often starts as a small papule or collection of papules, which break down to form small ulcers with a so called cat's paw appearance. These coalesce and the central area then undergoes necrosis to form a single ulcer.

Recent clinical studies

Etiology

Genco RJ
J Periodontol 1996 Oct;67(10 Suppl):1041-9. doi: 10.1902/jop.1996.67.10.1041. PMID: 8910821

Diagnosis

van der Valk P, Herman CJ
Lab Invest 1987 Feb;56(2):127-37. PMID: 3543488
Patrone F, Dallegri F, Rebora A, Sacchetti C
Blut 1979 Oct;39(4):265-9. doi: 10.1007/BF01013219. PMID: 497407

Therapy

Genco RJ
J Periodontol 1996 Oct;67(10 Suppl):1041-9. doi: 10.1902/jop.1996.67.10.1041. PMID: 8910821
Yoda S, Morosawa H, Komiyama A, Akabane T
Am J Dis Child 1980 May;134(5):467-9. doi: 10.1001/archpedi.1980.02130170017007. PMID: 7377154
Patrone F, Dallegri F, Rebora A, Sacchetti C
Blut 1979 Oct;39(4):265-9. doi: 10.1007/BF01013219. PMID: 497407

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