[CIS PIDD] Degenerative encephalitis in DOCK8

[Dewton Vasconcelos]

Dear friends and colleagues

I am writing this e-mail asking for suggestions for a young man, 19 
years old and born to a consanguineous couple presenting in infancy a 
probable viral pneumonia leading to BOOP and subsequent pulmonary 
infections.
When he was 4 years old he presented a severe viral meningitis, needing 
ICU treatment, that eventually cured without sequels.
Disseminated eczema since childhood, followed by warts at 14 years of 
age, associated to four episodes of skin squamous cell carcinomas (HPV+).
At 16 years he presented rapidly progressive lost of sight, becoming 
amaurotic since then.

He was sent to our evaluation with almost 18 years old, blind and with 
disseminated warts.
The immunological investigation showed low IgM, high IgE and IgA 
(polyclonal), Leuko: 15320; Lymph: 7% (1072); CD3: 69.3% (743); CD4: 
43.9% (471); CD8: 23.0% (247); CD19: 18.5% (198); NK: 5.9% (65).
Lymphoproliferation showed low responses to mitogens (PHA, OKT3, PWM) 
and absent responses to antigens (Candida, PPD, CMV, VZV, tetanus toxoid 
and toxoplasma); NK cell lytic activity: virtually absent;
Lymphoproliferation stimulated by PMA+ionomycin: Low; Response to IL-2 
and IFN-alpha in vitro: Normal;

Genetic testing (whole exome sequencing - NIH): Homozygous large 
deletion in DOCK8 gene;
After that we are searching for a HSCT donor (brother 100% HLA 
disparity); No matched unrelated donor found until now.

Approximately five months ago he started to present mild ataxia, being 
evaluated by neurology and evidenced disseminated CNS atrophy. CSF 
normal, PCR negative for Herpes 1-2, Adeno, JC and BK virus.

Three months ago his ataxia worsened quickly, leading to gait 
difficulty. We again asked for a neurology evaluation (thinking about a 
neurogenetic disease) and they suggested astrovirus infection.
We again looked for viruses: Herpes 1-8; Adeno; Entero viruses; 
Astrovirus; Sapovirus; Norovirus; JC and BK; Yellow fever and 
arboviruses (all negative twice by PCR).

There was evidence of oligoclonal bands in CSF, then we began to treat 
him with 2 g/kg IVIg. He came to the second infusion of IVIg much worse, 
with a severe ataxia, incapable of speaking and walking.

There are 4 DOCK8 patients in the literature presenting neurologic 
degeneration, two of them secondary to JC virus and 2 without diagnosis.

What do you think that we could do to diagnose and treat this patient.

I would be very grateful for any thoughts, suggestions and comments.

Dewton


Dewton de Moraes Vasconcelos, MD, PhD
University of São Paulo School of Medicine
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