[PAGID] R: WAS with normal mpv

[Notarangelo, Luigi]

Dear Rohan:

I apologize for the delay (you had contacted me directly, but I was not in town).
We have identified the E133K mutation in three patients, all of which had classical WAS. However two of these patients were referred to us from other colleagues, and there were no data on the MPV. The third patient is a child I took care of. He also had classical WAS (very severe thrombocytopenia, very severe eczema and multiple and severe infections) and died early in life of CNS hemorrhage (he was not transplanted because of lack of a suitable related or unrelated donor). His MPV was consistently very low (4 fL). One key consideration is that MPV is very difficult to evaluate. False low MPV values are common in patients with severe thrombocytopenia; on the other hand, aggregates may lead to false-normal (or near-normal) MPV values in WAS. At the time I saw the child I mentioned, we did not perform a thorough analysis of the platelets, so the values I gave are the ones in the medical records.
Importantly, we could not perform WASP protein expression analysis on his platelets or fresh blood cells, because he died prior to cloning of the WASP gene.

Best regards

Gigi


Luigi Notarangelo
Professor of Pediatrics, Harvard Medical School
Division of Immunology, Children's Hospital
Karp Research Building, 9th floor, Rm 09210
1 Blackfan Circle
Boston, MA 02115
USA
tel: 617-9192277



-----Messaggio originale-----
Da: pagid-bounces at list.clinimmsoc.org per conto di Rohan Ameratunga
Inviato: dom 7/6/2008 7:23
A: pagid at list.clinimmsoc.org
Cc: Lochie Teague
Oggetto: Re: [PAGID] WAS with normal mpv
 
Dear Colleagues,

 

We would like your advice on two brothers with WAS, one aged 3 yrs and
other 18 months.  The older child presented with severe thrombocytopenia
(platelets <10) and severe eczema.  He had otitis media.  No visceral/
deep seated infections.  The younger boy was born with similar symptoms
and had one intracerebral bleed.

 

After discussion we performed mutation analysis and both have an E133K
mutation, suggesting a severe WAS phenotype.

 

What is very unusual is that both have had persistently normal mpvs
(7.5-8 FL)

 

Both have been transplanted.  The older one had a MUD while the younger
one had his mother's marrow.

 

Patients with mutations of the CDC42 region of WASP can have normal mpvs
but the phenotype is completely different from classical WAS. 

 

We would like to further investigate why these WAS children have a
normal mpv.  Our review of the literature has not explained why the mpv
is so low in WAS.  

We have considered a reversion event but this would be unlikely in two
individuals.

 

I have already discussed these children with several former North
American colleagues.  Thanks for their responses.  

 

Any other thoughts would be very much appreciated.

 

I am copying this to the family's peds haematologist in case any other
clinical details are needed. 

 

Best regards

 

Rohan Ameratunga

Adult and paediatric immunologist

Auckland

NEW ZEALAND