[CIS PIDD] Degenerative encephalitis in DOCK8

[Bodo Grimbacher]

Dear Dewton,

I think the CNS involvement is part of the phenotype (Dock8 deficiency).
Please see attached the initial clinical description of this condition by
Renner et al. in 2004.
They all turned out to have Dock8 deficiency.

And here is what we find in our cohort of Dock8-deficient children:

CNS features: 13/34 pts (38%)
JC virus-associated progressive multifocal leucoencephalopathy: 2 pts
Meningitis: 4 pts
CNS vasculitis: 3 pts
Encephalitis: 1 pt
Stroke: 3 pts
Fungal abscess: 1 pt
Vascular aneurysm: 1 pt


So basically you have to be prepared for everything :-(
I hope this helps.

Yours, Bodo


Am 26.07.12 23:57 schrieb "Dewton Vasconcelos" unter <dmvascon at usp.br>:


>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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