At the founding of the organization, the cause of Elijah's Syndrome was unknown, and he was officially "undiagnosed". However, he has since been diagnosed as having a WARS2 deficiency. This site was established to begin educating all who are interested in learning, and hopefully, build a community of similar patients as well as families and friends willing to support these patients.

Elijah's Journey


Elijah's birth was without medical complications, and he seemed to be a healthy baby. In hindsight, there were two observations that may have been early indicators to his syndrome. First, he had some tremors that have persisted. We were told by all medical professionals it was considered normal for a newborn to have tremors while their nervous system developed. Second, he had poor weight gain and was much thinner than either of his younger brothers. Newborns lose weight shortly after birth and regain within a matter of days; however, it took Elijah months to regain the weight lost after birth. For this reason, he was classified as "failure to thrive" for a while. It wasn't until Elijah was about nine months of age before his pediatrician considered something may be wrong and began referring him for further evaluation.

As Elijah grew, he began to miss developmental milestones. Initially, he seemed normal as he would try to climb someone holding him. His head control was shaky, but he could turn it from side-to-side. At about four months, he began to turn over, which wasn't a serious concern. The closest proximity to crawling was achieved at about 13 months and consisted of using his hands to pull himself forward. Independently getting into the traditional crawl position has never been achieved with all attempts resulting in him falling to either side or face-forward. "Crawling" on hard floors allowed him to slide, but carpet was extremely difficult for him to have any movement. He never crawled far because he would fatigue quickly. At about 19 months, he began making sounds that resembled "dah" and "buh". Unfortunately, at the same time the Norovirus swept through our household and impacted Elijah the worst. He became incredibly lethargic and had significant difficulty sleeping. His sleeping was never good as he never slept through the night. As a newborn, he woke about every hour, which is not considered too abnormal. However, his sleep didn't progress beyond three to four hour stretches prior to his Norovirus infection at about 20 months. His nights are still restless at the age of six years. No other physical development milestones have been achieved.

Elijah's many specialists have performed many diagnostic tests, with few findings. All blood tests by his pediatrician, neurologist, gastroenterologist, endocrinologist, etc. returned as normal or near enough to normal that no concerns were raised. The neurologist ordered a 24-hour EEG due to his tremors, eye rolling, drooling, and spastic movements with all being observed during the study resulting in a negative test result. A few MRIs of his brain and spine have returned as "normal". Less than two months after his Norovirus infection, he had his first lumbar puncture (spinal tap). The results were within normal, but his neurotransmitters were not assessed. The first major "breakthrough" came with his second lumbar puncture at under 2.5 years. It was found that his dopamine levels were minimal and he had high levels of 3-O-methyldopa. The initial suspicion was tyrosine hydroxylase deficiency, and he was quickly put on a regiment of sinemet (levodopa/carbidopa). With this finding, the geneticist began the process for a whole exome sequence. Ultimately, the result of this sequencing was negative since tyrosine hydroxylase was found to be "normal" and the top three possible mutations found were improbable. Since the whole exome sequence was negative, he had whole genome sequencing. Again, this was negative and tyrosine hydroxylase was still considered "normal". There was one interesting observation from his genome, an unstudied gene known as ZNF718 was missing a section in the middle, which has since been found to not be the primary cause of Elijah's Syndrome. Two years later, his genome was reanalyzed, and the WARS2 gene was identified. The WARS2 gene is discussed in detail here including the evidence it could be a likely cause of Elijah's Syndrome.

After his first lumbar puncture, he began having sporadic episodes of profuse sweating with cries of pain, which were relatively frequent for months and continued until after five years of age when he began receiving clonazepam to reduce his tremors and fisting. What has been noticed during this time is Elijah's reduced sense of pain or a delayed response to pain. For example, he had cut open his heel and never showed a response in spite of heavy bleeding. Prior to starting clonazepam, he would seem to have moments of muscle pain, possibly caused by muscle cramps, that would be accompanied by profuse sweating and fussing. He still has moments of profuse sweating that may be accompanied by fussing.

As mentioned previously, the first medication tried was sinemet (levodopa/carbidopa). The intent was to start "low" at 1 mg/kg and slowly rise to 10 mg/kg. Lower doses had no observable effect, mild improvements at moderate doses, and good improvements with serious side effects at the higher doses. At the higher doses, he had improvements in his sleep, tremors, eye rolling, fisting, constipation, and fatigue; however, his dyskinesia was severe as well as the increased thirst that reduced his appetite. His poor response to sinemet and many symptoms mirror what has been described as tyrosine hydroxylase deficiency type B; however, genetic testing has not revealed a known mutation of the tyrosine hydroxylase gene. The current plan has been to use a combination of medications to improve his symptoms and minimize the side effects.

Based on the symptoms observed, Elijah's Syndrome appears to be primarily a nerve condition since he lacks coordinated motor control, tires easily, and has a poor response to pain. He does not seem to have weak muscles since it can require two adults to change a diaper or get him into a chair. While the excessive drooling and constipation are likely due to poor muscle motility, this may again be due to an underlying issue with the nerves that innervate these muscles. In addition to the nerves, the adipose (fat) tissue is also adversely impacted by Elijah's Syndrome since he does not gain weight except when he undergoes a growth spurt. Poor weight gain is not a nerve condition, so it must be due to common mechanism, the mitochondria. In late 2017, a paper titled "Biallelic mutations in mitochondrial tryptophanyl-tRNA synthetase cause Levodopa-responsive infantile-onset Parkinsonism" was published about WARS2 describing a situation similar to Elijah. Individuals with a WARS2 deficiency have similar symptoms with a broad range of severity in these symptoms. Thus, his current diagnosis is a WARS2 deficiency.

Symptoms at a Glance



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