June 11, 2014

NIH, Day 3

Today was the day Bertrand went under general anesthesia for a battery of procedures.

It was a hard day for Bertrand.

Bertrand had a good night's sleep, even though his IV kept kinking up and bringing the nurse in to fix it.  (He slept right through it each time.)

His day started at 6:30am:



They couldn't pull his blood at 7:00am because his IV was letting fluids in, but not out.

Fortunately, since fluids were still going in, they didn't need a new IV for anesthesia.

I held his hand as he went under for four hours of scans, biopsies and tests.

His orders while out were:
  1. an MRI/MRS scan on his head and brain (90 minutes);
  2. an auditory brain response test;
  3. an opthalmological exam;
  4. retinal photography;
  5. nasal-gastric tube insertion to extract stomach fluids for pH testing;
  6. a Schirmer's moisture test for eye moisture;
  7. a lumbar puncture to extract cerebrospinal fluid;
  8. a skin biopsy from his forearm to grow fibroblasts; 
  9. blood draw; and
  10. a dental exam.

Bertrand always gets eerily still under general.

Bertrand's body, even asleep, is riddled with tiny tugs and jerks.

These little movements have become an almost imperceptible background noise over time.

When that background noise fades out, it's louder than ever.


While Bertrand was under, we met with genetic counseling to construct a family tree annotated with any factors of (possible) genetic significance.

We then met with Dr. Lyons, an immunology researcher.  Dr. Lyons went into detail explaining even more effects of CDGs on the immune system with a focus on allergies.

CDGs are proving to be a fascinating way to study the immune system.  The spectrum of CDGs systematically break individual parts of the glyco-pathways involved in immune processes.

That allows scientists to observe the effects of the breaks at each point and to infer relationships between glycobiology and the immune system.


When Bertrand woke up, he was upset:



Unfortunately, we couldn't feed him yet because the nasal-gastric tube remained, and had to remain until they collected a sample of gastric fluids.  (During the procedure, nothing was coming out of the tube.)

His stomach had a lot of gas.


He calmed down quickly, gave us a few smiles and then passed out.


He woke up briefly to watch some Elmo:


 We had to run a new IV under ultrasound, since his old one couldn't collect blood any more.

Just like last time, they found only one suitable vein.

Just like last time, they got it on the first try.


We tried to feed him when we got back, but he threw up three times.

Zofran settled his tummy, and then he passed out for the evening.



In the afternoon, we had long conversations with Lynne Wolfe and Christina Lam about preliminary findings and hypotheses.

We have some early findings and confirmations:
  1. Bertrand's tear ducts produce normal levels of moisture, yet he never cries.
  2. The dry eyes could be caused by physiological problems with the eyelids.
  3. Bertrand's stomach acids have a normal pH: 1.5.
  4. Bertrand's ears appear to work, but there are processing problems with the nerve leading to the occipital lobe.
  5. There is atrophy in his optic nerve.
  6. There is unexpectedly low protein in his cerebrospinal fluid (CSF).  (Lynne Wolfe explained that if neurons were dying, we would expect that protein to accumulate in the CSF.  This is a going to be an interesting puzzle to solve.)
Many more results are on the way as tests are run on the samples and data collected today.

An intriguing hypothesis

Lynne Wolfe also shared an intriguing hypothesis about a mechanism of harm when thinking about the moisture problems in NGLY1 patients and the possibility of mucin deficiency.

(Mucin is a key protein in lubrication, but it's O-linked. Lynne's hypothesis can explain how an N-linked disorder can create an O-linked deficit.)

What's really interesting about the hypothesis is that it focuses on downstream pathway problems from NGLY1 deficiency, whereas we've mostly been focusing on the upstream (glycoprotein accumulation) problems.

She stressed that it's only a hypothesis at this point, but it points in the direction of interesting tests to run.

If she's right, it also points toward other routes for developing treatments.

I was really intrigued by this possibility, because until now, I'd considered misfolded glycoproteins themselves as the sole source of harm.

Much more work needs to be done to test this hypothesis.

Fortunately, Lynne and Hudson Freeze are already on top of it.

If it holds, it's going to be a big step in the right direction for the NGLY1 patients for both understanding and treatment.

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