Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia.
We identified 18 patients with the distinct clinical phenotype of susceptibility to disseminated nontuberculous mycobacterial infections, viral infections, especially with human papillomaviruses, and fungal infections, primarily histoplasmosis, and molds. This syndrome typically had its onset in adulthood (age range, 7-60 years; mean, 31.1 years; median, 32 years) and was characterized by profound circulating monocytopenia (mean, 13.3 cells/microL; median, 14.5 cells/microL), B lymphocytopenia (mean, 9.4 cells/microL; median, 4 cells/microL), and NK lymphocytopenia (mean, 16 cells/microL; median, 5.5 cells/microL). T lymphocytes were variably affected. Despite these peripheral cytopenias, all patients had macrophages and plasma cells at sites of inflammation and normal immunoglobulin levels. Ten of these patients developed 1 or more of the following malignancies: 9 myelodysplasia/leukemia, 1 vulvar carcinoma and metastatic melanoma, 1 cervical carcinoma, 1 Bowen disease of the vulva, and 1 multiple Epstein-Barr virus(+) leiomyosarcoma. Five patients developed pulmonary alveolar proteinosis without mutations in the granulocyte-macrophage colony-stimulating factor receptor or anti-granulocyte-macrophage colony-stimulating factor autoantibodies. Among these 18 patients, 5 families had 2 generations affected, suggesting autosomal dominant transmission as well as sporadic cases. This novel clinical syndrome links susceptibility to mycobacterial, viral, and fungal infections with malignancy and can be transmitted in an autosomal dominant pattern.
Vinh
Donald C
DC
Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Patel
Smita Y
SY
Uzel
Gulbu
G
Anderson
Victoria L
VL
Freeman
Alexandra F
AF
Olivier
Kenneth N
KN
Spalding
Christine
C
Hughes
Stephen
S
Pittaluga
Stefania
S
Raffeld
Mark
M
Sorbara
Lynn R
LR
Elloumi
Houda Z
HZ
Kuhns
Douglas B
DB
Turner
Maria L
ML
Cowen
Edward W
EW
Fink
Danielle
D
Long-Priel
Debra
D
Hsu
Amy P
AP
Ding
Li
L
Paulson
Michelle L
ML
Whitney
Adeline R
AR
Sampaio
Elizabeth P
EP
Frucht
David M
DM
DeLeo
Frank R
FR
Holland
Steven M
SM
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005658:Fungi; D030342:Genetic Diseases, Inborn / Q000097:blood / Q000150:complications / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007958:Leukocyte Count; D007970:Leukopenia / Q000097:blood / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium; D009164:Mycobacterium Infections / Q000097:blood / Q000209:etiology / Q000235:genetics*; D009181:Mycoses / Q000097:blood / Q000209:etiology / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000209:etiology / Q000235:genetics*; D009369:Neoplasms / Q000097:blood / Q000209:etiology / Q000235:genetics; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000097:blood / Q000209:etiology / Q000235:genetics*; D010375:Pedigree