[CIS PIDD] [cis-pidd] MTHFR, Pitt Hopkins and Immunodefiency

Mon Apr 27 13:44:13 EDT 2015

Dr. Brooks,

Yes, I am aware of the previous immunological studies which have been authored regarding patients with Pitt Hopkins Syndrome and pDC function.  I am interested in treating and exploring her immunoglobulin deficiency, which is different than has been previously reported (as you mentioned, in the past only IgM deficiency has been reported).  

1) I was looking for anyone who has given IVIG or SQIG to patients with MTHFR homozygous mutations; none to my knowledge have been reported in the literature.  I have already read the nice review that screening for MTHFR mutation in patients with thrombosis may not be necessary (as noted by Dylan Mordaunt here), and we are checking for fasting total
plasma homocysteine as a result of that literature.  I was looking for cases of patients who have successfully received IVIG or SQIG with homozygous MFHFR mutations without evidence of thrombosis through this forum.

2) I was looking for other patients with Pitt Hopkins and CVID-like phenotypes to explore this immunological phenotype.

Warmly,
David

-- 
David Rosenthal, D.O., Ph.D.
Adult, Adolescent and Pediatric Allergy, Asthma, and Clinical Immunology
Medical Director, Center for Young Adult, Adolescent and Pediatric HIV
Attending Physician, Division of Allergy/Immunology
North Shore-LIJ Medical Group 
865 Northern Blvd, Suite 101  •  Great Neck, NY  11021
P: 516-622-5070  
F: 516-622-5060
E: drosenthal at nshs.edu

Assistant Professor of Medicine and Pediatrics
   Hofstra North Shore-LIJ School of Medicine 

Laboratory of Host Defense
The Feinstein Institute for Medical Research
   P: 516-562-1185        F: 516-562-1107

-----Original Message-----
From: Brooks, Edward G [mailto:brookse at uthscsa.edu] 
Sent: Monday, April 27, 2015 11:13 AM
To: CIS-PIDD
Cc: Cody, Jannine D
Subject: RE: [SUSPECTED MARKETING] [cis-pidd] MTHFR, Pitt Hopkins and Immunodefiency

Dr. Rosenthal,

Your case is very interesting. As you may know, the TCF4 gene mutation may lead to defects in plasmacytoid dendritic cell function and reduced production of interferon-alpha (Cisse, B., et al. (2008). Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135, 37-48.) Specific B- and T-cell developmental abnormalities have not been documented thus far. Some authors have reported reduced IgM levels, but CVID has not been reported. 

We have a center specifically devoted to the evaluation and treatment of patients with Chromosome 18 disorders and a specific program for Pitt-Hopkins Syndrome(PI: Janine Cody, PhD). We would be grateful if you would consider referring your patient to our center website (to www.pediatrics.uthscsa.edu/centers/chromosome18). The family can directly enroll their daughter if they are interested. Our current project involves enrollment and longitudinal medical record review collection. We have an NIH grant pending for clinical evaluations and immunological/neurological assessments.

Sincerely

Ed Brooks

Edward G. Brooks, MD

Eloise Alexander Professor

UT Health Science Center at San Antonio

8403 Floyd Curl Dr. MC 8259

San Antonio, TX 78229

Tel: 210-562-4180

Fax: 210-562-4191

-----Original Message-----

From: David Walter Rosenthal [mailto:drosenthal at lij.edu] 

Sent: Friday, April 24, 2015 1:06 PM

To: CIS-PIDD

Subject: [SUSPECTED MARKETING] [cis-pidd] MTHFR, Pitt Hopkins and Immunodefiency

Hello all…

I have a patient who is a 12 year old female with TCF4 gene mutation (Pitt-Hopkins Syndrome), Homozygous MTHFR mutation (C677T) and CVID phenotype/hypogammaglobulinemia who has recurrent sinus infections requiring rotating antibiotics and tonsillar hypertrophy, vitamin A deficiency.  IgG 412 mg/dl, IgA 21 mg/dl, IgM 18 mg/dl, IgE 10 IU/ml.  Low normal antibody titers.  Relatively normal T/B/NK lymphocyte enumeration with CD19 slightly low (184 cell/ul, 8%).  Normal PHA/PWM proliferation. She has classic symptoms of Pitt-Hopkins including developmental/speech/motor delay, recurrent seizure, craniovertebral instability, hyponatremia.

1)	Based on her low immunoglobulins and recurrent sinopulmonary infections, I would ideally like to give her subcutaneous immunogloblulin, but I am concerned regarding hypercoagulability with patients with MTHFR homozygous mutations and the risk for thromboembolism.  Does anyone have experience in giving IVIG or SQIG to any patient with homozygous MTHFR mutation?  Any recommendations from others?

2)	If anyone else has a patient with Pitt-Hopkins with CVID phenotype/hypogammaglobulinemia, please contact me, I am considering some additional studies and these would benefit from another case or two which have a similar clinical immunophenotype.

Warmly,

David  

--

David Rosenthal, D.O., Ph.D.

Adult, Adolescent and Pediatric Allergy, Asthma, and Clinical Immunology Medical Director, Center for Young Adult, Adolescent and Pediatric HIV Attending Physician, Division of Allergy/Immunology North Shore-LIJ Medical Group

865 Northern Blvd, Suite 101  •  Great Neck, NY  11021

P: 516-622-5070

F: 516-622-5060

E: drosenthal at nshs.edu

Assistant Professor of Medicine and Pediatrics

   Hofstra North Shore-LIJ School of Medicine 

Laboratory of Host Defense

The Feinstein Institute for Medical Research

   P: 516-562-1185        F: 516-562-1107

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