May 31, 2012

Complications from Depakote

The likely culprit for Bertrand's recent hospitalization was depakote.  This has been the most effective seizure medication for him to date, but it has many nasty side-effects.  We were aware of many side-effects, including liver damage, and were monitoring him for symptoms.  Now we have to watch for a few more: hyponatremia (low sodium) and bone marrow suppression.

Bertrand caught a typical virus.  (He goes to preschool, therapy, dance, playgroup... he could've caught a bug anywhere.)  And then entered a vicious cycle, due to undiagnosed hyponatremia and bone marrow suppression.  The hyponatremia alone could've killed him.  Normal values are 135 mEq/L.  He was at 4 mEq/L.  The bone marrow suppression resulted in low counts for all blood cell types--white, red, and platelet.  To fight an infection, you need plenty of all of the above.

We are incredibly lucky that Bertrand got sick exactly when, where, and how he did.  He was already in the hospital (for a different procedure), with the A-Team for doctors.  They acted fast, and he is now on the mend.  Bertrand sure knows how to keep things interesting!

A few more items learned from this week:

The targeted dosing greatly changed Bertrand's nighttime EEG!  He is no longer in status epilepticus at night, which means the valium protocol is no longer right for him.

The looping episodes, of which multiple were caught on EEG, are NOT seizure activity.  In fact, Bertrand's EEG is almost normal at those times.  These are periods of alertness and a manifestation of his movement disorder.

Once Bertrand is well, we will conduct another sleep study to see if apnea is waking him at night, thereby triggering those looping episodes.

We will also see about lowering/eliminating Depakote, and/or we may continue to tweak his medication dosing to target the night seizures better.  As a substitute for Depakote, Bertrand may try Clobazam.

Next Monday, Bertrand has appointments with his pediatrician and his metabolic doctor to follow-up.  He'll be getting labs drawn then too.

To be on the safe side, I've ordered some salt tablets for him.  Each pill contains: 215 mg sodium, 63 mg potassium, 11 mg magnesium, 22 mg calcium, 100IU Vitamin D.  Bertrand can take 1,200mg of sodium per day, so depending on what he has to eat on any given day, he may get 1 or several.

Paranoid much? me?!  Nah.

May 29, 2012

Hospication* Update

Victoria (with titi Beli's help) made a card for Bertrand.
I'm exhausted, so here's the quick overview:
  • Bertrand is hospitalized with no discharge set.
  • The valium protocol is on indefinite hold.  (This may actually be for the best.  More on this later.)
  • Bertrand's temperature and sodium (which was very low) are normalizing.  
  • His WBC, RBC, platelets have all come back low and liver values have re-elevated.
  • A working theory is that depakote may have slowly given Bertrand hyponatremia (low sodium) which could be exacerbated by a virus.
  • Another less likely theory is sepsis.
  • A blood culture is pending.  Other cultures (strep and urine) have returned normal.
* A light-hearted explanation of the term "hospication" (hospital + vacation) can be found on my friend Niki's blog HERE.

May 28, 2012

Valium Protocol - Failure to Launch?

Bertrand battles a possible UTI as well as seizures.
As mentioned way back when, Bertrand was to undergo the Valium (aka Riviello) Protocol.

Maddeningly, the neurology team at our hospital fumbled his admission for months.

So, the head of pediatric neurology decided to oversee Bertrand's initiation himself.

This afternoon, Bertrand was finally admitted for the procedure.

And promptly developed a fever and possible infection.

He is currently being evaluated for strep and UTI.

Depending on Bertrand's condition tomorrow, the protocol could be halted before it even began.

Seeing Bertrand sick is sad, but the thought of months more seizures is heartbreaking.  :'(

Here's hoping our little buddy gets well soon.

May 25, 2012

The Return of Atonic Seizures

The last 5 seconds of the video capture the drop attack.

For the past couple of weeks I've been trying to fool myself into thinking that Bertrand was just having some really big myoclonus. Nope. It's clear the drop attacks (atonic seizures) are back.

The last time we saw Bertrand have a drop seizure was in May 2010.  ACTH treatment, while it almost killed him, bought us 2 years of drop freedom.  Now, we're going back in the ring to fight them.

May 21, 2012

Photos from Dance Performance

More backstage photos from Bertrand's 5/13/2012 dance performance.

May 16, 2012

Is your child undiagnosed?

8 month-old baby Bertrand.
Extreme cuteness may also be a symptom.
Since the identification of Bertrand's NGLY1 mutations, researchers are hoping to find/test previously undiagnosed children for the same condition.

potential N-glycanase enzyme treatment has been identified.

I need help finding undiagnosed kids fitting this profile. Matching kids may be eligible to receive a test for this newly discovered genetic (NGLY1) disorder.

The salient features are:
  • Developmental delays
  • Involuntary movements starting in infancy
  • Liver dysfunction detected in infancy- elevated transminases and AFP, all normalized at this time
  • Myoclonic seizures starting in infancy
  • Lack of tears
The presentation of kids with NGLY1 mutations may vary with severity.  Both Bertrand's mutations are located toward the end of the gene, so he may actually be one of the less affected.

The undiagnosed children may have been extensively tested for congenital disorders of glycosylation and lysosomal storage disorders, returning normal results.

Thanks for any help you can provide!

May 15, 2012

Doose Syndrome Research Study

The Doose Syndrome Epilepsy Alliance in coordination with the Gene Partnership at Children’s Hospital Boston and the Manton Center for Orphan Disease Research is proud to announce a new research project.
This is an exciting step for us. If your child has a Doose syndrome diagnosis (myoclonic astatic epilepsy aka epilepsy with myoclonic atonic seizures) then we want you! This is a new sequencing pilot project for clinical and research use. This initiative will allow for investigators at Children's Hospital, with approved IRB protocols, to submit samples for whole genome sequencing or exome sequencing. An inadequate understanding of Doose syndrome’s underlying causes is the greatest obstacle standing in the way of new treatments and cures for orphan diseases, like Doose syndrome. Many disorders are lumped together under a single diagnostic umbrella, making it difficult for physicians to identify appropriate and safe treatments. Further studies could uncover an underlying genetic flaw and open avenues of research to treat or correct the error.

Instead of individual scientists working in "silos" to understand specific orphan diseases, the Manton Center fosters collaborations between investigators to share ideas, resolve common challenges and attack orphan diseases from multiple perspectives. The Manton Center's environment also attracts new experts and resources to address challenging issues, accelerating the discovery process.

Armed with the necessary research tools, financial support and collective determination, investigators at Children's Hospital have created an interdisciplinary program to narrow the gap that separates the study of orphan diseases from mainstream medical research.

The first step to involve yourself in this critical research is to register your interest with Heather Jackson at Please call directly at 719-491-7340 if you have further questions. From there I will connect you with our contact to ensure that all of the data on our Doose syndrome children is submitted and ran together, which will strongly increase the probability of making links.  This research will be conducted at no cost to you, however the investigators will have to coordinate orders for blood work with your physician.

Best Regards,  
Heather Jackson
Doose Syndrome Epilepsy Alliance 

What if my child has "probable Doose syndrome" or their diagnosis has changed? Please by all means please register.
What if I am not in the US? No problem we will work with your physician to ensure participation.
What if I am not a patient at Children's Hospital Boston? Not a problem, you will consent.
Will I have to travel? No, you will do the blood work at your local lab with orders from the Manton Center.

May 14, 2012

Clinical application of exome sequencing in undiagnosed genetic conditions

The first article citing Bertrand's genetic condition was just published in the Journal of Medical Genetics!  Our family (Bertrand, Cristina, and Matt) comprises Trio 2.  This article (PDF) was published under the Creative Commons License, so please spread the word about this fantastic study.  :)

Clinical application of exome sequencing in undiagnosed genetic conditions

  1. David B Goldstein1,4
+Author Affiliations
  1. 1Center for Human Genome Variation and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
  2. 2Department of Pediatrics, Section of Medical Genetics, Duke University, Durham, North Carolina, USA
  3. 3Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA
  4. 4Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA
  1. Correspondence toDr David Goldstein, Center for Human Genome Variation, Duke University School of Medicine, Box 91009, Durham, NC 27708, USA;
  1. Contributors AN: study design, data analysis and interpretation and manuscript writing. VS: patient recruitment and counselling, clinical follow-up, study design, data interpretation and manuscript writing. YH: laboratory follow-up of candidate variants, data interpretation, manuscript writing and figures. KSchoch: patient recruitment and counselling, clinical follow-up, data interpretation and manuscript writing. KShianna: sample preparation, genotyping and genotyping quality control and manuscript writing. MHM: data interpretation, figures and writing. DBG: study design, data interpretation and manuscript writing. MTM: patient selection.
  • Received 10 February 2012
  • Revised 14 March 2012
  • Accepted 2 April 2012
  • Published Online First 11 May 2012


Background There is considerable interest in the use of next-generation sequencing to help diagnose unidentified genetic conditions, but it is difficult to predict the success rate in a clinical setting that includes patients with a broad range of phenotypic presentations.
Methods The authors present a pilot programme of whole-exome sequencing on 12 patients with unexplained and apparent genetic conditions, along with their unaffected parents. Unlike many previous studies, the authors did not seek patients with similar phenotypes, but rather enrolled any undiagnosed proband with an apparent genetic condition when predetermined criteria were met.
Results This undertaking resulted in a likely genetic diagnosis in 6 of the 12 probands, including the identification of apparently causal mutations in four genes known to cause Mendelian disease (TCF4, EFTUD2, SCN2A and SMAD4) and one gene related to known Mendelian disease genes (NGLY1). Of particular interest is that at the time of this study,EFTUD2 was not yet known as a Mendelian disease gene but was nominated as a likely cause based on the observation of de novo mutations in two unrelated probands. In a seventh case with multiple disparate clinical features, the authors were able to identify homozygous mutations in EFEMP1 as a likely cause for macular degeneration (though likely not for other features).
Conclusions This study provides evidence that next-generation sequencing can have high success rates in a clinical setting, but also highlights key challenges. It further suggests that the presentation of known Mendelian conditions may be considerably broader than currently recognised.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: and

May 13, 2012

What it means to be a mom

Today I say thank you to an incredible mother: my wife, Cristina.

Cristina--indeed, many mothers of special needs children--have shown me that the only truly inexhaustible resource is a mother's love for her child.

Special needs moms are just ordinary moms thrust into extraordinary circumstances.

And the character that emerges from those circumstances is telling.

I say emerges because I don't think those circumstances forge that character.

I believe those circumstances reveal that character.

So, what has Cristina taught me about motherhood?

Being a mom means hoping when all hope is lost.

It means fighting when you know you cannot win.

It means believing the crippled will stand and walk.

It means believing the mute will speak.

It means believing the blind will see.

Motherhood is about never yielding to the impossible when your child is on the line.

It is about exerting a force of will so strong that, even if for only the briefest of moments, the line between the possible and the impossible bends.

It is about exerting that force for so long and with such intensity that, in rare circumstances, that line breaks.

I think every mother is prepared to do the impossible for their child.

Luckily, most moms never have to.

It has been a privilege to watch my wife do it for our son, Bertrand.