[CIS-PAGID] NZ infant with PJP

[Jan Sinclair (ADHB)]

Dear PAGID members

Would appreciate any thoughts on a male infant, now 6 months old.   New Zealand born, South East Asian parents, non consanguineous. 1st child to this couple.   Early oral candida, responding to treatment but recurring each time treatment stopped.

He presented at 3 months of age with:
*          Pneumocystis pneumonia, problematic course needing prolonged intensive care stay, complicated by biopsy proven pulmonary alveolar proteinosis (managed with repeated pulmonary lavage), now well from a respiratory point of view.
*          Failure to thrive and chronic diarrhoea.  Negative for all GI pathogens (bacterial and viral including PCR), upper and lower scope with normal pathology on 2 occasions.  Diarrhoea improved with TPN and now gaining weight but unable to transition back to oral feeds.

Investigations:
*         Thymus present on first CXR
*         Normal / raised lymphocyte count (most often 6-12 x 109/l)
*         No rash, no hepatosplenomegaly, and no adenopathy
*         Mild metaphyseal dysplasia, skeletal survey otherwise no abnormality
*         Phenotype (repeated over time and essentially unchanged)
CD4      49    %           Absolute CD4      6138    X10E6/L
CD8      22    %           Absolute CD8      2755    X10E6/L
CD4:CD8 ratio      2.2
CD3      70    %           Absolute CD3      8823    X10E6/L
CD19      27    %         Absolute CD19      3451    X10E6/L
CD56      2    %           Absolute CD56      297    X10E6/L
*         TREC                                normal
*         Vb repertoire                     polyclonal
*          No maternal engraftment
*          Immunoglobulins               presentation    Feb      Mar      Now
IgG                               1.7                   IVIG      IVIG      IVIG
IgA                               0.29                 0.48     <0.07   0.11
IgM                               0.06                 1.8       0.17     0.12
*          CD40L normal

Proliferation:
At presentation                       PATIENT                                 CONTROL
                                    cpm                 SI                     cpm                 SI
Background                 122                                          26
PHA                             1409                11.5                 27539              1059.2
CON A                         1747                14.3                 7265                279.4
CD3 Response           67                    0.5                   4696                180.6

On repeat testing these have improved markedly, most recently:
                                     PATIENT       SI                    Control          SI
Background                 432                                       70
PHA                             138930         321                  111031         1586
T3                                16128           37                    47781           683
PMA                             3931             9                      9100             130
Ionomycin                    320               1                      238               3
PMA + Ionomycin        47755           110                  229807         3283


The initial thought was that he may have a T cell activation defect.  Calcium flux studies were kindly undertaken by Prof Stefan Feske in New York, which were normal, excluding ORAI1 or STIM1 as the underlying defect.

Early in his course the plan was to consider HSCT, with good cord matches available.  We are currently not hurrying in that direction, with normalisation of his proliferation, a slew of other normal investigations, and no diagnosis.  However he is still TPN dependent and his immunoglobulin results suggest loss of IgA and M production.

Any thoughts (underlying defect / other investigations / treatment options) would be welcome.

Dr Jan Sinclair
Paediatric Immunology
Starship Children's Hospital
Auckland, New Zealand
Ph            (64 9) 307 8900 extension 6429
Fax          (64 9) 307 8977 (internal 5977)
Mobile      021 365 445


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