This study will examine the symptoms, course of disease and treatment of non-tuberculous
mycobacterial (NTM) infections, as well as the genetics involved in these infections.
Patients with NTM have recurrent lung infections and sometimes infections of the skin and
other organs as well. They may also have curvature of the spine, barrel chest, and heart
valve weakness. The study will compare the features of NTM with those of Job syndrome and
cystic fibrosis, other diseases involving recurrent infections of the lungs and possibly
Patients with diagnosed or suspected non-tuberculous mycobacterial infection, cystic fibrosis
or Job syndrome may be eligible for this study. All participants will have a medical and
family history, blood and urine tests, imaging studies that may include X-rays, computed
tomography (CT) or magnetic resonance imaging (MRI) scans, and DNA and other genetic studies.
In addition, all patients with Job syndrome and cystic fibrosis, and patients with NTM who
have lung disease undergo the following procedures:
- Scoliosis survey X-rays of the spine to look for curvature or other abnormalities of the
- Echocardiography imaging test that uses sound waves to examine the heart chambers and
- Electrocardiogram measurement of the electrical activity of the heart
- Pulmonary function tests breathing tests to measure how much air the patient can move
into and out of the lungs
- Body measurements measurements of height, weight, arm span, finger length, etc.
- Joint function assessment of joint mobility using different maneuvers to test
flexibility of joints and ligaments
- Examination of physical features that might be associated with NTM, such as high arched
palate of the mouth, flat feet, or certain skin features
- Dermatology (skin) examination for reactive skin conditions or other skin problems and
possibly a skin biopsy (surgical removal of a small skin tissue sample for microscopic
- Interview with genetics specialist
These tests may require several days to complete. Patients with NTM will also be examined by
a cystic fibrosis specialist and may have a sweat test. In addition, NTM patients will be
asked to return to NIH every year for 5 years for follow-up tests, if medically indicated,
including CT of the chest, scoliosis survey and examination by other specialists.
The nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms foundin soil and
water that rarely cause disease in humans. Since exposure to these organisms is universal and
disease is rare, it can be concluded that normal host defenses are almost always sufficient
to prevent infection. It follows that otherwise healthy individuals who develop disease must
have abnormal susceptibility or immune defects that permit infection with nontubercuolous
mycobacteria. The organisms that are most commonly encountered in clinical practice include
Mycobacterium avium, and M. intracellulare [collectively known as the M. avium complex
(MAC)], M. kansasii, M. fortuitum, M. abscessus, and M. chelonae. These organisms share
significant structural and biochemical similarities with their more pathogenic relative, M.
tuberculosis (MTB). Recognition of host factors that predispose or lead to NTM infection may
have important implications for pathogenesis and therapeutic intervention, and may be
applicable to the more virulent MTB. Identification of genetic or acquired susceptibility
factors may lead to recognition of endogenous pathways that can be exploited therapeutically
and to possible gene identification.
Over the last two decades, three important observations have been made regarding the
pathogenesis of nontuberculous mycobacterial infections. 1) In patients infected with HIV,
nontuberculous mycobacterial infections often occur when the CD4+ T-lymphocyte number falls
below 50/mm3. This suggested that specific T cell products or activities were required for
mycobacterial resistance. 2) An association was noted between pulmonary nontuberculous
mycobacterial infections and a particular body habitus, predominantly in post-menopausal
women (pectus excavatum, scoliosis, mitral valve prolapse). 3) Multiple defects have been
found involving the interferon gamma synthesis and use pathways in patients with disseminated
nontuberculous mycobacterial infection without HIV, suggesting this is a critical pathway for
host defense against these organisms.
We seek to better characterize the predisposition to mycobacterial infection. This study will
specifically address several aspects of immune function and investigate the proposed link to
body morphotype in the relevant population. By collecting this information, we hope to
provide insight into disease associations, infection susceptibility, and genetic
predisposition to mycobacterial infection.
- INCLUSION CRITERIA FOR PATIENTS:
This protocol will study patients with mycobacterial infections, including those without
previously identified predisposing disease processes as well as individuals with underlying
Patients with nontuberculous mycobacterial infections will be of particular interest, as we
are interested in isolating and characterizing the primary immune defect(s) responsible for
this infection susceptibility.
Select patients with acquired immunodeficiencies or tuberculosis may also be studied if
relevant host defects are suspected.
Patients must be referred to NIH with a diagnosis or suspicion of having mycobacterial
Male and female patients will be accepted without limitations due to age.
Only patients with nontuberculous mycobacterial infections without HIV infection will be
considered for long-term disease management.
INCLUSION CRITERIA FOR RELATIVES:
As part of this protocol, we may obtain medical records, family member questionnaire, blood
work, urine, saliva or buccal swab from some blood relatives of patients on the study, with
the hope of isolating and characterizing the primary immune defect(s) responsible for
mycobacterial infection susceptibilityand if there are any genetic links seen within
families. We hope to identify families with an apparent genetic susceptibility to
respiratory diseases predominantly associated with P-NTM and perform whole genome
sequencing within this group to identify genetic mutations accounting for this increased
susceptibility. Male and female patients will be accepted without limitation due to age.
These relatives will not receive treatment or have any other protocol procedures done
unless they become a patient on the study.