Thank you!

I would like to thank, from the bottom of my heart, everyone who has commented, emailed, phone called, or text messaged their support! Apparently, you all don't think I am completely nuts! I really appreciate it and Bertrand does too. :) You have all bolstered my courage for tomorrow's "thesis proposal"!

Plenty of pictures & video of Bertrand will be coming soon--I promise. But, tonight I am busy preparing the documentation to present to Bertrand's neurologist in the morning while baking for the Cookies for Cole bake sale in the afternoon. We're hoping to scoop-up sales from with the Univ. of Utah football traffic. If you have the urge for something sweet, you should stop by! :)

Speaking of sweet, here is a video of Victoria's first time in a jumper yesterday. She is an old pro at it now. Don't you just want to eat-up those chunky little legs?! She reminds me so much of Bertrand when he was this age--except that he was sitting better, barrel-rolling, and pulling himself to sitting. She has big shoes to fill. ;)

My "Ph.D.": A diagnosis for Bertrand

Today, Bertrand saw a corneal specialist for his eyes. Followers of this blog know of Bertrand's protracted battle against corneal erosion and his alacrima (lack of tears) since birth.

The two ophthalmologists who saw Bertrand today, noted the scar on his right cornea but, other than that, found no evidence of corneal erosion. Bertrand did NOT have dry eyes.

Furthermore, at home, Bertrand has been crying tears. This is especially remarkable because Bertrand still had severe xerophthalmia (dry eyes) just four short days ago.

This was the second successful test of what I am calling "my thesis". If every parent claims to be the expert in their child, I am attempting to get my PhD in Bertrand Might.

MY THESIS:

Liver damage, resulting in vitamin B12 & vitamin A deficiency, induced developmental delays, neuropathy, seizures, and alacrima.

Now, please let me explain.

I believe that Bertrand was born with liver damage because the jaundice Bertrand had at birth was not severe, but he could not shake it on his own. He had so much difficulty that he was hospitalized in the NICU. Bilirubin, the cellular byproduct that causes jaundice, is usually processed by the liver.

This liver damage could be the result of an unknown genetic disorder or the result of an infection.

While I took the best of prenatal care with Bertrand (vitamins, diet, doctors appointments, etc.), I caught "colds" twice: once in the 1st trimester and once in the 3rd trimester. I was pretty miserable.

Bacterial and viral infections can cause liver damage. Obviously, the most well-known of the viral ones are called Hepatitis A, B and C, but Mononucleosis (commonly referred to as "mono") can cause liver damage as well, and there are others.

Such an infection could have damaged Bertrand's liver prenatally and possibly my own.

(This is a big assumption, but it can in part be tested by checking Bertrand for antibodies of liver damaging viruses & bacteria. Since he hasn't had such an illness in his life, the presence of such antibodies would have come from in utero.)

The liver is where vitamins A, B12 and D are stored. It holds approximately a 3 year supply of each. If this supply is damaged, one is reliant solely on diet. Bertrand's diet for the first 5 months was breast milk. I wager that my milk was low on these vitamins, and the amount of these vitamins found in formula just were not sufficient given any pre-existing liver damage.

And here is where things get a little perverse. Certain medications block the absorption of vitamins B12 and A: proton pump inhibitors and H2 receptor antagonists. These are the antacids also known as prevacid and zantac.

What was Bertrand's very first medication? You guessed it. Zantac, followed by Prevacid. (In hindsight, this is also around when his seizures started. Coincidence?)

Based on this, could Bertrand be vitamin B12 and vitamin A deficient?

What are signs of severe vitamin B12 deficiency?

• Neuropathy
• Movement disorder (chorea, twitching)
• Seizures
• Macrocytic anaemia

Obviously, Bertrand has these. Multiple nerve conduction studies, EMGs, EEGs and MRIs serve as evidence.

B12 is a primary component of the myelin sheath found on all nerves.

Do you remember the MRI which I posted a few days ago? That was a case of B12 deficiency and it closely resembled Bertrand's MRI.

B12 deficiency is almost always associated with malnutrition. It is not a first world disease. So, hematologically, it is associated with macrocytic anaemia, which can include folate, B6 and iron deficiency as well.

However, Bertrand's case is NOT one of malnutrition. Bertrand has plenty of the vitamins which don't require liver storage.

What does B12, and only B12, deficiency look like in the blood? It looks like really fat red blood cells (macrocytosis) and/or excess platelets (thrombocytosis), for unknown reasons.

Yup, at his last blood draw, Bertrand had elevated MCH and MCV (measures of macrocytosis). And early on, he had elevated platelets.

What are signs of severe vitamin A deficiency?

• Nyctalopia - night blindness
• Xerophthalmia - dry eyes
• Follicular hyperkeratosis - a kind of bumpy skin

I don't know about Bertrand's night vision, but he definitely had xerophthalmia and follicular hyperkeratosis.

I say "had" because by this point, you can probably guess that we began vitamin B12 supplementation 2 weeks ago and vitamin A supplementation 4 days ago.

With vitamin B12, he became more vocal and alert within hours. By day 3 his myoclonic seizures (jerks) stopped. By day 6, his night seizures stopped. By day 7, he was walking in his gait trainer. By day 11, we lowered his seizure medication and we have seen no seizures.

Back to today's ophthalmology appointment, that was the first test of the success of vitamin A. We could tell that his eyes (& skin) had improved some within about 24 hours, but we've proceeded cautiously with the dose. Unlike B12 which is water-soluble, Vitamin A is fat-soluble and can be toxic. We're being cautious not to overdose.

According to the medical literature, in cases of vitamin B12 deficiency, symptoms can be completely reversed--if caught early. EEGs normalize after about 5 weeks and there are MRI changes by 10 weeks.

Unfortunately, Bertrand's case, if it is one of vitamin B12 and A deficiency, was NOT caught early. We should assume that there will be permanent brain and nerve damage.

But that hasn't stopped me from shooting him up with omega-3 fatty acids for myelin sheath repair or researching intensive therapy options. As with most "scientists" (if I dare call myself such), optimism comprises my core. ;)

SO...

The way I see it, my "thesis proposal" is this Thursday, with Bertrand's neurologist. Then I get a few months to test and, in essence, watch "my dissertation" develop. And at some point, an EEG and MRI should serve as my defense!

And, better than any sheepskin diploma, I will get a healthy, happy son!

1st Annual Conference on Rare Diseases & Orphan Products

Stellar Lineup of Speakers Announced for U.S. Conference On Rare Diseases And Orphan Products Join all stakeholders – patient advocates, researchers, government, industry, investors – in this 1st annual summit featuring thought leaders and focusing on collaboration! You are invited to the 1st Annual U.S. Conference on Rare Diseases and Orphan Products to be hosted by the National Organization for Rare Disorders (NORD) and the Drug Information Association (DIA). Additional support for this conference is being provided by the Food and Drug Administration (FDA), National Institutes of Health (NIH), European Rare Diseases Organization (EURORDIS) and Duke University School of Medicine. There will be separate tracks for patient advocates and organizations, researchers/drug and device companies, and investors. The conference will incorporate the well-received rare disease investigators training course offered by FDA for the first time last year. NORD is the voice of the nearly 30 million Americans who have rare diseases. DIA is a nonprofit, global professional association of more than 18,000 members who are engaged in the discovery, development, and management of pharmaceuticals, biotechnology, medical devices, and related health care products. The event will take place October 11-13 at the Omni Shoreham Hotel, Washington DC. Speakers will include: NIH Director Francis S. Collins, MD, PhD Social Security Commissioner Michael J. Astrue, JD John F. Crowley, Chairman and CEO, Amicus Therapeutics Fred Hassan, MBA, Partner, Warburg Pincus, Chairman of the Board, Bausch and Lomb Mark B. McClellan, MD, PhD, Director, Engelberg Center for Health Care Reform, The Brookings Institution Frank J. Sasinowski, MPH, JD, Partner, Hyman, Phelps & McNamara Jeffrey Shuren, MD, JD, Director, Center for Devices and Radiological Health, FDA Janet Woodcock, MD, Center for Drug Evaluation and Research, FDA Margaret Anderson, Executive Director, FasterCures Kelly C. Slone, Director, Medical Industry Group, National Venture Capital Association Suzanne L. Bruhn, PhD, Senior Vice President, Strategic Planning & Program Management, Shire Human Genetic Therapies For patient advocates and patient organizations, there will be a separate track of presentations focused on strategic planning, growth, and effective advocacy for the patient community. In addition to the three tracks, all stakeholders will join together in high-level plenary sessions to discuss how the various interests can collaborate more effectively. If you can only attend one rare disease/orphan product conference this year, this should be the one! It will provide a unique opportunity for thought leaders from all perspectives to address the issues and seek ways to drive progress toward safe, effective treatments for patients. REGISTER ONLINE NOW! Limited scholarship assistance may be available for patient representatives Online registration for this unique event is now open on the DIA website. For representatives of patient organizations, limited scholarship assistance may be available. Patient representatives interested in applying for scholarships may write to Audrey Ashley at NORD (aashley@rarediseases.org) and request an application form. There will also be limited exhibiting space for companies and organizations. Inquiries about this may be directed to Shannon Lewis at DIA (shannon.lewis@diahome.org).Tel 215 442-6149. THREE TRACKS FOR PARTICIPANTS Attendees will benefit from discussions on the FDA and NIH processes, health care reform, changes in insurance reimbursement, off-label issues, and de-risking investments. Specific topics for the three tracks will include: For Researchers, Drug and Device Companies: Senior medical officials from FDA and NIH will discuss product development, how to develop a new product, and how to comply with NIH grant and FDA approval requirements. The conference will provide a platform for addressing the unique challenges faced by companies in the development of orphan products and how to avoid common pitfalls. Industry leaders and senior agency officials will discuss how to work with federal agencies on everything from grants to orphan designation and clinical development to product approvals. For Patient Advocates and Patient Organizations Learn how you can become more effective advocates for the patients you represent. Learn about the new and emerging federal policies that affect patients with rare diseases. Learn how the government and private sector are addressing the special challenges faced by patients in the new health care environment. Meet individuals who run patient organizations efficiently and creatively to advance the interests of patients and how best to organize for effective advocacy. For Investors: Explore the new concept of venture philanthropy and how it will affect research funding. Gain a better understanding of how the FDA and NIH work and how they interact with the drug and device development processes. Learn ways to de-risk your investments in orphan products and understand better the timelines for research and regulatory reviews.

Crying Tears.

Bertrand is crying real tears. The only change in his daily regimen has been the addition of a B-12 supplement.

We are using a transdermal B12 patch and oral B12 supplement.

Of course, I've been on a research binge for the past few days. Here are some bits and pieces floating through my head...

• B12 is stored in the liver. (Bertrand has liver damage.)
• B12 is water soluble. (An overdose on B12 is near impossible.)
• B12 is expressed in bile.
• Actigall (ursodiol) is a bile acid. (Bertrand's liver has improved on actigall.)
• B12 deficiency in infants causes movement disorder & developmental delay...

When Bertrand was a baby, we'd thought for certain that he was a case of B12 deficiency. His neurologists shot this theory down because of the important fact that Bertrand was/is not anemic. Folate can mask B12 deficiency, but he should still show some signs of anemia.

But this image is haunting me:

The MRI above is from THIS article, entitled "Involuntary Movements and Magnetic Resonance Imaging Findings in Infantile Cobalamine (Vitamine B12) Deficiency", published in PEDIATRICS: Official Journal of the American Academy of Pediatrics back in 2003.

Does "bilateral periventricular symmetric high-signal lesions in the white matter on T2-weighted images" sound familiar?

You can bet this will be discussed with Bertrand's pediatrician on Tuesday!

Corneal Erosion: Genetic Condition or Side-Effect?

Victoria "styling" Bertrand's hair this morning.

This is just a quick update (read: vent) on what I've been up to regarding Bertrand. Since his keppra wean, he has been having the least number of seizures since ACTH! As a result, he is also more vocal and interactive. Unfortunately, the seizures that he IS having are sleep-related and disturbing to watch. More on that later.

All summer Bertrand's corneal erosion has not improved despite eye drops or ointment every 2 hours. In case you are wondering, that is $50 worth of eye goop every week. It is also a very upsetting process for Bertrand and time-consuming for us. And yet, I am plagued by the feeling that I am losing the battle to save his eyes. If he is this bad now, in the summer, with a humidifier in his room, how bad will it get in the dry Utah winters?!

I've been feeling defeated. It's not a feeling I am comfortable with, so I got to thinking...

It was not always this way. While Bertrand didn't cry tears (alacrima), he wasn't battling constant eye infections and corneal erosion. This all started back in January, before depakote, but a month AFTER ADDING LAMICTAL. A quick google search confirmed that dry eyes are a common enough side-effect of lamictal.

After leaving 2 messages with neurology and 2 emails to her, I finally heard back from Bertrand's neurologist last night. I feel like she blew me off. Bertrand's eyes and seizures could wait until she could see him at his September 20th appointment.

NO. WAY.

My baby boy has suffered long enough. Corneal erosion is extremely painful. As per my last discussion with his ophthalmologist, Bertrand is facing surgery to sew his eyes partially shut to reduce the amount of surface area and thereby the moisture he loses by them. As it is, his corneal scar is occluding his pupil and damaging his vision.

This is unacceptable.

Yes, seizures suck, but Bertrand needs to be seen as a whole. It is possible that depakote may be enough to control his seizures. Or maybe lamictal isn't to blame and he does need the surgery. Either way, we need to test and see because Bertrand deserves this chance.

I've spent the morning fighting for my boy, calling in the "big guns". Wish me luck.

UPDATE:

This afternoon, I spoke with Bertrand's Pharmacist (the one who once opened the pharmacy on a Sunday just for us, after we forgot to pick up his medication). According to him, Lamictal can cause dry mouth and other ocular issues, but "dry eyes" as a symptom were not in his literature. He recommended some eye ointments/drops that were new to the market. He also recommended a prescription about which we should speak to Bertrand's ophthalmologist.

From my own research, I learned that Lamictal is a (modest) inhibitor of the enzyme dihydrofolate reductase, which completes the two-step activation of dietary folate into the bioactive form, tetrahydrofolate. A B-12 deficiency would increase the adverse effect potential of the Lamictal. Dry eyes can be a symptom of B-12 deficiency...

So, TONIGHT, Bertrand starts some new sublingual vitamin B supplementation (THANKS, AMY!) and new eye drops. ;) Bertrand will see his pediatrician about all of this on Thursday. His neurology appointment was moved up a little earlier to September 1st. Grr.