NGLY1 Profile: Tim, age 3

Patient: Tim*, age 3

Parents: C and A

Sibling(s): none

"Tim" was born in June 2011 by Cesarean section at 39 weeks after fetal distress was noted.  He weighed only 2.3 kg at birth - intrauterine growth restriction (IUGR) had been noted at around 34 weeks of pregnancy and a biopsy of the placenta showed necrotic tissue. He had mild hyperbilirubinemia which did not require treatment, but otherwise his neonatal course was unremarkable and we were discharged on day three.

It was not long after that our journey began. Something seemed not right with Tim. He was crying inconsolably, not sleeping well, he moved different from other babies, he could not hold up his head very well (and he kept on nodding – we only realized much later that those nods were seizures! No doctor had picked it up). He was floppy and lying in a C-shape. He did not like to be touched or soothed. He did not like noisy environments or other people in general. He was fussy. Somehow he always managed to reach his milestones just in time in those first months and since he was feeding well, no doctor got concerned. They always sent us home with words of encouragement such as “all babies are bad sleepers” or “some boys tend to develop more slowly” but we just KNEW that something was not right!

At 6 months we took him to a neurologist and she immediately confirmed our worst fears. Our son had “brain damage” and no, there was nothing we could do but try to ease the symptoms and carry on with our lives. We were devastated! We got Tim admitted to a big university hospital in Germany and all sorts of tests were done. It was so scary and unreal. Many results came back slightly abnormal (one of them was for CDG which in the end happened to be a close match to NGLY1 deficiency), but it was all unspecific and we were discharged with no diagnosis and even more fear than before. We had:

• global developmental delay
• generalized poly-spike discharges in the EEG
• elevated blood lactate levels
• elevated LFTs
• delayed myelination in the MRI

Soon after, Tim’s seizures started to get worse (we are pretty sure they had been there before) we started a long journey of finding the right medication. This journey led Tim to another hospital stay of almost two months. He had myoclonic jerks of arms and legs and nodded with his head (atonic seizures). We kept close track of the frequency. What started out with 20 seizures a day went up to 200 while the doctors kept changing his meds again and again. Tim was miserable. He got worse from day to day. He could barely move anymore and stopped smiling. The doctors started telling us that “this was the nature of his progressive disease”. A second MRI showed his brain was shrinking. It was horrifying.

Somehow, for lack of a better idea, doctors declared him to be a suspected case of mitochondrial disease. As one doctor put it “this is the only label under which we can combine the EEG and the liver findings”. We were so frustrated with these doctors and the hospital in general!

After some months we took him out of the hospital and off the meds, but we still had no diagnosis and no idea where we were headed. We started to note involuntary movements and Tim kept on getting eye infections which resulted in corneal scarring – we first blamed the high-dose steroid therapy while actually these were fundamental symptoms of his disease. He could not close his eye lids during sleep. He was severely constipated. His sleep pattern was highly pathological with hardly any deep sleep and many arousals during the night. He was constantly tired, and so were we.

On the positive side, time showed that his regression during the hospital stay was not due to his progressive disease but due to the treatment. The longer Tim was out of the hospital the more he recovered. A new MRI in spring 2013 – although still showing abnormal results like the first one – showed that Tim’s brain had re-gained its volume. We started milder interventions for treating the epilepsy like the ketogenic diet and phased meds in and out very slowly and not as abruptly as in the hospital. Still, except for Lamictal more than a dozen medications showed no effect or only negative side-effects. Lamictal helped at least a little bit with his sleep and mood. Tim’s greatest motor achievement during that time was learning to belly crawl a few months before his second birthday.

In the summer of 2013, briefly before his second birthday, I did an internet search for “ketogenic diet check up protocols” and found Cristina’s blog. I saw pics of Bertrand and immediately started reading about his symptoms. He looked and sounded so much like Tim!!! So I sent the Mights an email and received a reply the same day. We were so excited! They too thought Tim was a close match and put us in touch with their doctors. We sent his skin cells and DNA to the States and bam…a few weeks later we had a diagnosis! Tim was the first child to be only tested for NGLY 1 deficiency (and not whole exome/genome sequencing) and the 10th child to receive the diagnosis. He is the only German child so far.  

Having a diagnosis has changed everything. We are no longer alone, but are in this together with some of the most wonderful families imaginable. The exchange between the families has been tremendously helpful and I am sure will continue to be so as we are working on finding a cure. Also, based on Bertrand’s experience and because we had run out of other options we were able to convince our doctors to put Tim on Valproate for his seizures (they had not dared to do so earlier because of his suspected mitochondrial disease). It took a long while (almost 6 months and increase up to 600 mg/day), but he became seizure free. He has been seizure free for more than three months now (knock on wood). He is a changed child. He has learned to sit up, to come on his hands and knees, to feed himself, and to take supported steps during this time. He babbles the whole day, and is so much happier and calmer than before.

“Overcomingmovementdisorder.com” has changed our lives and we’ll be eternally grateful to Cristina and Matt. We want to encourage all parents to never give up the search for a diagnosis – even if there is no cure yet, it can make a huge difference in your child’s and your own quality of life!

* Name has been changed to protect privacy.