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Mitochondrial disease and immunodeficiency: What do we
know so far?
Susan Pacheco M.D.
Associate Professor, Pediatrics
Co-Director, UT Mitochondrial Center
Allergy and Immunology
University of Texas, Houston
OBJECTIVES
Explain why consider immunological problems
in children with mitochondrial disease
Provide basic guidelines for the evaluation
and treatment of infections and potential
Immune problems in children with
Mitochondrial disease
IMMUNE SYSTEM
AVAILABLE PUBLISHED REPORTS
WHAT IS REPORTED BY CARETAKERS
WHAT WE THINK IS HAPPENING
WHAT WE ARE DOING
Background
Mitochondrial Disorder
Lack of ATP production
Organs with high energetic demands
What happens with the immune system?
Description of mitochondria and immune function is absent from all major reviews and textbooks on mitochondrial
medicine published so far.
Debray 2008, DiDonato 2009, DiMauro 2003, Morova 2006,Shapira 2003, Sheffler 2007 , Wallace 2010, Zeviani 2007, DiMauro 2006
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Severe, often fatal infections in individuals with defined
mitochondrial syndromes like MELAS, Pearson’s-Kearns-Sayre overlap syndrome, and infections
with unusual pathogens like Aspergillus
McKee 2000
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Severe, often fatal infections in individuals with defined
mitochondrial syndromes like MELAS, Pearson’s-Kearns-Sayre overlap syndrome, and infections
with unusual pathogens like Aspergillus
MITOCHONDRIAL DYSFUNCTION
T-cell activation
B-cell stimulation
INNATE IMMUNE SYSTEM
INFECTION
T-cell activation
B-cell stimulation
107 cells/ 5-7 days
1 cell
103’s molecules/secon
d
Threshold
Dysequilibrium
Increased energetic demands
Tissue dysfunction based onenergetic needs
GI DysmotilityDevelopmental delay
FTTMyopathy
Heart diseaseSeizure disorder
Neuromuscular weaknessPancreatic inssuficiency
Visual defectsHearing defects
Neurogenic bladder
PATIENT DATA
“INFECTIONS THAT TAKE LONGER TO RESOLVE”
Out of a total of 35 individuals selected for this study (43% females, 57% males), 94% suffered from recurrent or unusually severe infections
Pacheco 2011
Twenty-nine children (ages 1 - 16)Repeated infections, hypogammaglobulinemia, and B-cell dysfunction was found
Preliminary data suggests the presence of immune dysfunction in
children with MD
Pacheco 2009
Increased catheter associated bloodstream infections and sepsis in
patients with:
Mitochondrial diseaseGI dysmotility
Parenteral nutrition
Pacheco 2011
DEFINITION OF IMMUNODEFICIENCY
“The strongest identifiers of PID are: family history of immunodeficiency, use of intravenous antibiotics for sepsis in children with neutrophil PID and failure to thrive in children with B-lymphocyte PID.” Subbarayan 2010
“Published warning signs are neither specific nor sensitive for PID”. MacGinnitie 2011
What are we doing?
Pacheco 2011
Screening of patients for potential immune defects
Prompt assessment and treatment of any metabolic decompensation and/or infection
PICU
IgG values
Aggressive treatment of infections
Promotion of routine and prophylactic vaccines
Children on parenteral nutrition and GI dysfunction with prior septic episode - Immune prophylaxis
