[CIS PIDD] [cis-pidd] ADA-SCID patient with dystonic movements

Tue Apr 28 23:56:54 EDT 2015

Thank you for the comments thus far. To follow-up:

--Thinking along your Neurology consultants: can you measure ADA-associated toxic metabolites in CSF (compared to the same metabolites in his blood)? Do they recommend PEG-ADA as a treatment modality?

1. The Neuro team did attempt to obtain studies for metabolites in his CSF but were unable due to low sample volume. We will definitely discuss if he gets repeat LP in the future.

2. Neuro does not comment on suspected utility of PEG-ADA as a treatment option. He’ll likely start this week while transplant work-up moves forward, so perhaps the answer will become clearer.

--I am intrigued by the twist in this story from Kawasaki Disease to ADA-SCID. Can you tell us more?

3. Re: Kawasaki disease (KD) to ADA-SCID: the team had been concerned about atypical KD given the 8 days of high fever. A TTE suggested a coronary artery aneurysm. Both cardiology and ID recommended treating for KD. We became involved shortly thereafter and the patient only received a single dose of IVIG (2g/kg) before SCID became the clearer diagnosis.

--I understand that movement disorders are uncommon in ADA-SCID, but have been reported in a few patients and in an animal model-http://www.sciencedirect.com/science/article/pii/S0887899407002275. Your description is probably more detailed and the observation of raised lactate on 1H-MRS is interesting. Are the parents consanguineous? What did the metabolic team at NIH think about the raised lactate?

4. The parents are not consanguineous.

5. We don’t have the NIH metabolic team on this case – I am seeing him at a children’s hospital (NIH only sees patients at least 2y of age). We’ve not had many comments on the elevated lactate seen on the MRS– do you have other thoughts? A lactate/pyruvate (serum) is pending. We were unable to get pyruvate from the CSF due to limited sample volume.

Thanks!
Rachel Sparks
Allergy/Immunology Fellow, NIH

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On 28 April 2015 at 05:06, Sparks, Rachel (NIH/NIAID) [E] <rachel.sparks at nih.gov<mailto:rachel.sparks at nih.gov>> wrote:
Hi All:

We would appreciate help with the following patient:

6mo AA male admitted with fever x 8 days, possible PNA, WBC = 30k, and severe lymphopenia. Family history notable for older brother who died at 4 months of age from respiratory infection. Patient initially treated with IVIG x 1 dose (2g/kg) for suspected Kawasaki Disease until flow cytometry showed absence of lymphocytes (T-B-NK-). Assay at Duke confirmed ADA deficiency. Patient treated with broad spectrum antibiotics, to include empiric treatment for PJP PNA based on CXR findings. Patient did well for 3 days until one week ago, when he developed rotary eye movements associated with whole body stiffening and tachypnea. CT head negative. LP showed 3 WBCs, negative culture and gram stain. Extensive ID work-up includes negative evaluations of CSF and blood (see list below).  MRI brain abnormal, to include signal abnormalities in the bilateral basal ganglia, thalami, brainstem and deep cerebellum. Reduced diffusion seen in the cerebral deep gray nuclei, right cerebral peduncle and internal capsule posterior limb, and mesial right temporal lobe including the hippocampus. Mildly elevated lactate and glutamine/glutamate in the left basal ganglia, suggestive of ongoing anaerobic metabolism and excitotoxicity. Video EEG monitoring demonstrated that these abnormal movements were not seizures. No prior history of neurological symptoms or illness. Neurological events continue several times daily, largely unchanged for the past week; they seem to be triggered in part by agitation and are improved with benzodiazepines.

Neurology in favor of attributing dystonic behavior and MRI findings to metabolic effects of ADA deficiency. They did not recommend additional metabolic work-up; urine and plasma amino acids normal. Immunology service concerned about infection. Repeat LP done, WBC = 8, gram stain and culture negative thus far, other repeat labs pending. Patient being treated with ceftriaxone (meningitic dose), Bactrim (PJP PNA dose) and fluconazole prophylaxis; ID following. Acyclovir discontinued after CSF HSV PCR negative.

ID work-up to date:
CSF: negative for adenovirus, parechovirus, EBV, HSV, enterovirus, VZV, HHV6, CMV, cryptococcus, toxoplasma. Bacterial, fungal and AFB cultures negative to date.
Serum: negative for HIV, adenovirus, EBV, CMV, RPR.

Question: any prior experience with similar dystonic movements and/or MRI findings in an ADA-SCID patient? Any additional infectious etiologies to evaluate for?

Thank you,

Rachel Sparks, MD

Allergy/Immunology Fellow, NIH

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