Download Presentation Title

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
Add text title
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
Add text title
Severe, often fatal infections in
individuals with defined
mitochondrial syndromes like
MELAS, Pearson’s-Kearns-Sayre
Add text title
overlap syndrome, and infections
with unusual pathogens like
Aspergillus
MITOCHONDRIAL DYSFUNCTION
Add text title
INFECTION
INNATE IMMUNE SYSTEM
T-cell activation
B-cell stimulation
T-cell activation
1 cell
107 cells/ 5-7
days
B-cell stimulation
103’s
molecules/second
Threshold
Dysequilibrium
Increased energetic demands
Tissue dysfunction based on
energetic needs
GI Dysmotility
Developmental delay
FTT
Myopathy
Heart disease
Seizure disorder
Neuromuscular weakness
Pancreatic inssuficiency
Visual defects
Hearing defects
r
Neurogenic bladde
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
Preliminary data suggests the
presence of immune dysfunction in
children with MD
Twenty-nine children (ages 1 - 16)
Repeated infections, hypogammaglobulinemia, and B-cell
dysfunction was found
Pacheco 2009
Increased catheter associated
bloodstream infections and sepsis in
patients with:
Mitochondrial disease
GI 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?
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
Pacheco 2011
UNIVERSITY OF TEXAS
MITOCHONDRIAL CENTER OF EXCELLENCE
713 500 7164
[email protected]
WWW.UTMITO.ORG