[CIS-PAGID] 8 year old girl with mitochondrialdisorder and severe infections

[Walter, Jolan]

We have an ongoing collaboration at MGH with Dr. Vamsi Mootha http://mootha.med.harvard.edu/ who is the Chair of Mitochondrial Medicine 2012: Capitol Hill, an upcoming meeting in June for scientist in the field of mitochondrial diseases.

Currently MGH beside Boston Children's and Tufts are all taking care of patients with mitochondrial diseases, and a small fraction of these patients have hypogammaglobulinemia or recurrent infections that is worsened by the indwelling lines for TPN. Some of the patients suffer from recurrent sinopulmonary infections other with yeast infections.



We have an IRB approved protocol to study these patients (and work as a team with MGH-based Neurology, Genetics and basic scientist in the Mootha Lab). The preliminary data shows heterogenous selection of immune defects  (T cell proliferation, decreased memory B cell compartment, low vaccine-specific response to Pneumococcus). A unifying feature is low lymphocyte count that further decreases with infections (neutrophil count can nicely increase). As if the lymphocyte would not have enough 'energy' to expand.



We would be glad to collaborate with other academic centers to increase awareness and understanding of these diseases.

Our immediate current goal is to collect evidence that IvIg replacement is important for a subgroup of these patients.



Thank you for sharing this case. Very relevant question.

Jolan



Jolan Walter M.D. Ph.D.
Instructor, Pediatric Allergy/Immunology
Massachusetts General Hospital for Children
Email: jewalter at partners.org<mailto:jewalter at partners.org> or jolan.walter at childrens.harvard.edu<mailto:jolan.walter at childrens.harvard.edu><mailto:jolan.walter at childrens.harvard.edu>
________________________________
From: pagid-bounces at list.clinimmsoc.org [pagid-bounces at list.clinimmsoc.org] on behalf of Boyce, Thomas G., M.D. [Boyce.Thomas at mayo.edu]
Sent: Tuesday, May 29, 2012 6:49 PM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS-PAGID] 8 year old girl with mitochondrialdisorder and severe infections

would be interesting to collaborate and write up a case series unless this is already well known in the literature.  i did not find much with my search.

________________________________
From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Daniel Conway
Sent: Tuesday, May 29, 2012 5:44 PM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS-PAGID] 8 year old girl with mitochondrialdisorder and severe infections

I have one young man presenting with mitochondrial deficiency, IgG of 150 at 11 years of age.  No febrile response to infections.  Pneumoniae (6), sinusitis, and enteritides were common and prolonged.

IgG replacement changed that and he has not had a pneumonia for 10 years.

Sincerely,
Daniel H. Conway, MD
Assistant Professor of Pediatrics
St. Christopher's Hospital for Children
Drexel University College of Medicine

On May 29, 2012, at 6:35 PM, "Nelson, Robert P Jr" <ronelson at iupui.edu<mailto:ronelson at iupui.edu>> wrote:

Dr. Boyce,
Yes, I ‘ve also wondered about this.  I have one child with antibody deficiency, mannose binding lectin deficiency, mitochondrial disorder and asthma.  Doing well on IVIG.
Bob
Robert P. Nelson Jr., MD
Professor of Medicine and Pediatrics
Divisions of Hematology/Oncology
535 Barnhill Dr. Ste 473
Indianapolis, IN  46202
Telephone: 317-948-1186
E-mail: ronelson at iupui.edu<mailto:ronelson at iupui.edu>
pager:  317-312-1773
From: pagid-bounces at list.clinimmsoc.org<mailto:pagid-bounces at list.clinimmsoc.org> [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Church, Joseph
Sent: Tuesday, May 29, 2012 6:29 PM
To: pagid at list.clinimmsoc.org<mailto:pagid at list.clinimmsoc.org>
Subject: Re: [CIS-PAGID] 8 year old girl with mitochondrial disorder and severe infections
Tom:
We (myself and our Geneticist) have identified a number of pediatric and adult patients with mito disorders and antibody deficiency.  Many of the issues with these patients are related to autonomic nervous system dysfunction (temperature regulation, gut dysmotility, chronic pain syndrome, fatigue).
They seem to have limited reserve in responding to infections that is not responsive to Ig replacement.
Joe Church
Children's Hospital Los Angeles
From: pagid-bounces at list.clinimmsoc.org<mailto:pagid-bounces at list.clinimmsoc.org> [mailto:pagid-bounces at list.clinimmsoc.org]<mailto:[mailto:pagid-bounces at list.clinimmsoc.org]> On Behalf Of Boyce, Thomas G., M.D.
Sent: Tuesday, May 29, 2012 3:23 PM
To: pagid at list.clinimmsoc.org<mailto:pagid at list.clinimmsoc.org>
Subject: [CIS-PAGID] 8 year old girl with mitochondrial disorder and severe infections

Do any of you see poorly characterized immune deficiencies in patients with mitochondrial disorders?

This is an 8 year old girl born at 32 weeks' gestation who spent 5 weeks in the NICU with multiple chest tubes for chylous effusions and pneumothoraces and mechanical ventilation for 14 days.  She had severe bowel motility problems and is now TPN dependent.  She has neurogenic bladder and has a vesicostomy.  She has a poorly characterized mitochondrial disorder with complex deficiencies in the electron transport chain.

Despite getting the inactivated influenza vaccine each year, twice she has developed severe ARDS and DIC with influenza, first in October 2009 and then in March 2011.  She will sometimes go into DIC with other infections as well, such as line infections with coagulase negative staph.  I measured her response to vaccine and she does make an immune response to influenza vaccine (and the infection).  After the second episode of severe complications associated with influenza, we have placed her on oseltamivir for the duration of the local flu season.  This year she did not get influenza (although it was a very mild flu year here).

Most of her other infections are recurrent UTIs which are presumably more anatomical in predisposition.

When she gets infection, she generally does not mount much of a febrile response.  She also does not develop leukocytosis.

Her labs are as follows (not during an episode of DIC):

Hb 11.9
WBC 3.7 (1.92N, 1.45L, 0.22M, 0.12E, 0.03B)
PLT 78
ESR 3
CD3 1161
CD19 107
NK 146
CD4 503
CD8 478
H/S ratio 1.1

B cell subsets essentially normal.
CD4 RTEs were adequate 119 (38%)

Igs are normal (IgG is supranormal as she gets IVIG monthly for autoimmune neuropathy)

Slightly decreased (but not absent) NK cell function.

Normal neutrophil oxidative burst.

Normal lymphocyte proliferative response to PHA but no response to tetanus toxoid.

Adequate tetanus and diphtheria serology (prior to starting on IVIG).

Very poor response to polysaccharide pneumococcal vaccine (postvaccination, she has titers >1.3 mcg/mL to only 6 of 23 serotypes).

Her specific mitochondrial defect remains undefined.  She clearly seems prone to severe manifestations of certain infections.  Are there other investigations that might characterize her immune susceptibility?

Thanks.

Tom

Thomas G. Boyce, MD, MPH
Pediatric Infectious Diseases and Immunology
Mayo Clinic
Rochester, MN 55905
phone: 507-255-8464
fax: 507-255-7767
Boyce.Thomas at mayo.edu<mailto:Boyce.Thomas at mayo.edu>

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