[CIS PIDD] Degenerative encephalitis in DOCK8

[dmvascon at usp.br]

Hi Bodo, good afternoon

Thank you very much for your advice. We will be prepared for the worse.

Best regards,

Dewton




Citando Bodo Grimbacher <bodo.grimbacher at uniklinik-freiburg.de>:


> 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

>

>