[PAGID] lymphopenic infant

[Luigi Notarangelo]

Dear Dr. Sinclair:

Indeed, a very interesting case.

I agree that Cernunnos or even DNA lig4 deficiency should be considered.
Cernunnos deficiency is usually leaky, and Lig4 deficiency has a spectrum of
phenotypes that fits with this one. Although no increased occurrence of
breaks were seen, the best assay would be survival of fibroblasts upon
irradiation. I would encourage to get a skin biopsy and perform this more
classical assay for radiation-sensitive PIDs. Other DNA repair defects
(including MMR defects, not only NHEJ defects) should be considered. Again,
something that could be worked out on fibrobalsts. Happy to help here and
sort out possible DNA repair defects in collaboration with Fred Alt, if you
wish.


Luigi D. Notarangelo, M.D.
Director, Research and Molecular Diagnosis Program on Primary
Immunodeficiencies
Division of Immunology, Children's Hospital
Professor of Pediatrics and Pathology, Harvard Medical School
Karp Building, 9th floor, Rm 09210
1 Blackfan Circle
Boston, MA 02115
USA

(tel) (617)-919-2276
(fax) (617)-730-0709






On 4/30/08 12:01 AM, "Jan Sinclair" <JanS at adhb.govt.nz> wrote:


> Hi all

> 

> I would appreciate any ideas about a patient:

> 

> 5 month old infant born in New Zealand. She presented to us at 4 months with

> failure to thrive, feeding difficulties and mild respiratory signs and

> symptoms, with PCP on BAL. Mild thrush. No nodes palpable and no

> hepatosplenomegaly.

> 

> ·       Indian parents (non consanguineous, and from different regions India).

> 

> ·       Ex 28 week gestation ­ uneventful neonatal course except for

> significant lymphopenia at birth (0.4 x 109) which has persisted since

> (0.4-0.7). 

> 

> ·       Mild neutropenia in first few weeks which had resolved. (Recurred this

> week with neutrophils 0.5)

> 

> Only other clinical finding is marked microcephaly (35.6cm; 4 cm<3%). Not

> dysmorphic. Eye exam, hearing, head ultrasound all normal and developmentally

> appropriate except for marked oral aversion needing ng feeds.

> 

> Other investigations:

> 

> ·       IgG 0.8g/l, IgA 0.4g/l, IgM 7g/l (was increased to 12g/l now back down

> to 7 ­ not monoclonal).

> 

> ·       Biochemistry normal, uric acid normal, ADA awaited.

> 

> ·       T and B cell numbers markedly reduced (CD3 50%, 295, CD4:CD8 3.1, CD19

> 20%, 118). NK numbers normal (25%, 148).

> 

> ·       Proliferation to PHA and CD3 normal (CPM equal to control, stimulation

> index ~80).

> 

> ·       No evidence T cell clonality looking at Vb by flow.

> 

> ·       No evidence maternal engraftment (clinically or chimerism).

> 

> ·       Karyotype normal XX.

> 

> ·       Wondered about Cernunnos but she is not radiosensitive with radiation

> studies reported as ³no increased breakage but a subpopulation of lymphocytes

> with an odd appearance (condensed in appearance - premature chromatid

> separation but no aneuploidy in that subpopulation)².

> 

> Clinically she is now well having finished treatment for PCP, on prophylaxis

> and IVIG replacement. Any thoughts or comments about possible underlying

> diagnosis / other investigations to pursue welcome.

> 

> With thanks, Jan

> 

> Dr Jan Sinclair

> 

> Paediatric Allergy and Clinical Immunology

> 

> Level 5, Starship

> 

> Private Bag 92024

> 

> Auckland, New Zealand

> 

>  

> 

> Phone: +649 307 4949 #6429

> 

> Fax: +649 307 8977

> 

> Mob: 021 365 445

> 

> E mail: JanS at adhb.govt.nz <mailto:JanS at adhb.govt.nz>

> 

>  

> 

> 



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