More than 360,000 babies are born each day world-wide, which, in general, is not such a rare event. However, when a baby is diagnosed with a rare disease after he or she is born, that becomes a rare event which in turn becomes a rare journey for the child and all those who come to know the child. There are 7,000 different types of rare diseases known today and nearly 50% of those affected are children - many who will not live to see their 5th birthday because their disease has no available treatment or cure.
The following details one father's journey with his firstborn son from discovery of his son's rare diagnosis through their daily challenges and successes today. As in all challenges in life, there are many things we learn through their story – most important of these is the need for continued support of research.
Meet Max, a father living in Arizona with his 9-year-old son Gage:
My firstborn son, Gage, was born in Yuma, Arizona on July 10, 2008 with a rare genetic disorder, Carnitine Acylcarnitine Translocase Deficiency (CACT), which falls under the umbrella of Fatty Acid Oxidation Disorders. The CACT disorder is considered rare as there have only been 30 cases world-wide submitted with the disorder.
It is suspected there are more, but due to an extremely high mortality rate of the disorder within the first 24 hours of birth, it is presumed that other cases are possibly submitted as Sudden Infant Death Syndrome (SIDS) instead of CACT.
Gage’s disorder was unknown at the time of birth because Arizona is one of the states that does not include CACT in their Newborn Screening panel. The symptoms of the disorder include low muscle tone, hypertrophic cardiomyopathy (thickened heart muscle), and liver dysfunction, among others. Gage presents all of these symptoms and is suspected to be the oldest living person with this severe type of rare genetic disorder.
NEONATAL SCREENING HISTORY & PRESENT DAY
Newborn Screening is a national program implemented by each state's health department. The program was started in the 1960s when a few doctors/geneticists realized that some rare genetic diseases had catastrophic symptoms in childhood that could be avoided or greatly minimized with early intervention.
A program was initiated to screen newborns within the time period necessary to provide treatment possibly preventing the worst aspects of many diseases. The Recommended Uniform Screening Panel (RUSP) includes a primary group of 27 diseases.
Since April 2011, all states are testing for the RUSP disorders. However, CACT is a disease for which 19 states either do not test or have a less than specific test reducing test accuracy. Unfortunately, Arizona is one of those 19 states.
Gage was immediately transferred to the Neonatal Intensive Care Unit post-birth for monitoring due to an unrelated medical symptom for the first few days of his life. It wasn’t until after he was cleared to be discharged that the genetic disorder began to reveal itself. After subjecting him to numerous tests in less than 24 hours, lab results finally pointed to the potential culprit – a rare genetic disorder.
The lab results showed a severely elevated ammonia level of over 800mcg/dl and climbing (a normal neonate is less than 100 mcg/dl). Gage faded into a coma and was taken by medivac to Phoenix Children’s Hospital, where they had the resources and expertise to address rare disorders.
When Gage arrived in Phoenix, his ammonia level was over 1000mcg/dl and he had settled into a deep coma. He was placed on a dialysis machine. After several hours on the machine, his ammonia levels decreased and he slowly receded from his deep coma state. Gage had unbelievably survived his near-death condition, but the next step was to keep him alive without specifically knowing what ailed him.
Considering the genetic lab test results would require more than a week’s time to receive, the hospital’s geneticist, Dr. Kyrieckos Aleck, started treating him under the assumption that Gage had CACT. Gage’s treatment stabilized him, and when the lab results showed that Dr. Aleck’s assumptions were accurate, the same treatment continued, but Gage’s prognosis was not good. Patients with CACT, if detected early on, survived only a few years at best, as the disorder affects many organs of the body, especially the heart.
The historical approach is to treat it with Medium Chain Triglyceride oil, but this regiment only stabilizes the disorder for a short period, until one of the organs, usually the heart, fails. Gage was treated under this assumption, and after about a month in the hospital he was discharged. Caring for an extremely, medically complicated child was, well, complicated. His heart muscle continued to thicken every day, and Gage was immobile due to low muscle-tone. I worried about how long he was going to survive; I expected it wasn’t going to be longer than a year.
Gage was in and out of the hospital for the next few months. When he was six months old, Dr. Aleck mentioned that he had learned about an experimental oil, Triheptanoin (C7), for treating patients with similar symptoms to Gage’s disorder. Dr. Charles Roe, at Baylor University, was experimenting with C7, which demonstrated to not only improve the muscular strength of patients within days, but also regressed the thickening of the heart, which was Gage’s foremost issue.
Dr. Aleck recommended the C7 for Gage, since the historical outcome was grim. Dr. Aleck spoke with Dr. Roe and he agreed to send the C7 on a compassionate basis. Gage received his first prescribed dose of C7 within a week.
RARE CIRCUMSTANCES SURROUNDING GAGE’S RARE CONDITION
Gage’s parents are both carriers (unbeknownst to them because the U.S. does not screen for carriers for all these rare conditions) which is a rare event for each of them to begin with. Then, they met and conceived together – two rare genotypes coming together, another rare event. Their odds with each pregnancy of bringing their two genes together into one baby were 1 in 4. More rarity. They happened to be living in Arizona when Gage was born, which was a 20/50 chance, not so rare on its own, but as such the odds of all these events occurring is somewhere around one in a million.
Had Gage been born in one of the other 31 states with neonatal screening for CACT, he could have been diagnosed in the first 48 hours and would have been treated with a special diet to avoid the brain damage and heart and muscle damage that he developed in his metabolic crisis within the first week of his life.
But then again, he was lucky to have been rushed to Phoenix within time, and where there was an experienced genetics department apprised in novel treatments including use of C7.
Another rarity is that the discovery and description of the genetic and biochemical defect in CACT deficiency must have been previously studied by genetics researchers who took an interest in studying the biochemical pathways that have failed in Gage and children with this genotype. It's likely that a grad student got their PhD thesis based on unraveling and analyzing exactly the defect at the molecular level, acting in obscurity, likely funded by NIH, proving that no matter how obscure something sounds when you hear about what a biomedical researcher works on, it is important.
After a few days of taking the C7 oil, Gage moved his legs in bed for the first time and his heart discontinued thickening. As time went on, he continued to improve his muscle tone and began using his legs and feet as most people would use their arms and hands, and even learned to manipulate his feet to pick up toys. To continue to take this oil and improve Gage’s health, he has since been included in the experimental clinical trials of C7. He visits the University of California, San Francisco twice a year, per study protocol, to get blood drawn for labs and to note his improvements: physically and mentally.
Although Gage has responded positively to the C7, his health remains extremely fragile, and it is still unknown if he will live from one week to the next. His health complications have him taking more than a handful of prescribed medications throughout the day and he is on a strict daily caloric intake through a feeding tube, since he cannot take anything orally. Gage is also required to be connected to an oxygen supply at all times, even using a bi-pap system overnight to assist his lungs with breathing.
The fragility of his immune system can also allow a simple cold to trigger a metabolic crisis and send him on a downward spiral to death within hours. It’s all a high-wire act of balancing and counteracting until his body hopefully fights off the infection and stabilizes. So far, he has been successful and is getting stronger each year, seeing numerous specialty doctors (e.g. geneticist, cardiologist, pulmonologist, and gastroenterologist) throughout the year to monitor his conditions.
Gage is currently unable to talk, but he screams whenever he’s happy, which is nearly all of the time. The origin of his lack of speaking words is unknown, as it’s not a symptom of CACT. However, Gage uses an Augmentative and Alternate Communication (AAC) device for communication at home and in his 3rd grade public school classroom. AAC is an electronic device with pictures that he can select so that the device can “talk” for him.
The most impressive thing I find is that although he is severely delayed in his speech, and many areas of life, he is capable of playing complex games on his iPad or any gaming station.
Gage is wheelchair bound due to his low muscle tone, but he can take about 3 or 4 steps if he pulls himself up to a standing position.
For now, he is a master at crawling around and climbing on furniture. He can even clap his feet together, like hands, with so much strength that the sound can be deafening. With everything, Gage is one of the happiest people I have ever come across. He is usually laughing at something, screaming with joy, or bouncing around.
He seems to take advantage of the time he has now and makes the best of it. Gage reminds me every time I see him that life is about enjoying every second and not worrying about things that I can’t control, which sometimes feels like just about everything.
WHAT RARE DISORDERS TEACH US
Some tragedies teach us a lot. Max and his family have the gift of a child whose every day may be his last and as such keeps them focused on the value of everyday. The biochemistry of children like Gage teaches researchers about the complex normal pathways in our cells/bodies that work to mostly keep our bodies working each day for decades.
It takes a huge village to reveal the mechanisms of human physiology and health. It takes a huge knowledge base that collectively brings the data together to make all that information useful to make better medical interventions and diagnoses. It takes a collective system to invest in basic research, applied research, and product development.
Meanwhile, families like that of Max and Gage LIVE the reality of a single gene gone awry and show how incredible the resulting tumble of symptoms and malfunctions is to manage. BioPontis Alliance is committed to being one piece of this essential system to translate discoveries, even those that seem obscure on its surface, into necessary medical care.
Max Sloss is first, and foremost, a father to his two sons, Gage and Mason. Mason is Max's second-born child and is 7 years old. Mason is only a carrier of CACT, and has no symptoms of the disorder. Max graduated with a BSEE from Temple University and is currently a part-time graduate student at the University of Arizona's Optics College. He works full-time as an electro-optical engineer for The Sensor Group in Tucson, AZ, performing research and development of advanced camera systems for military applications.
Dr. Barbara Handelin is co-founder and advisor of BioPontis Alliance. Dr. Handelin is a veteran entrepreneur and molecular medical geneticist who has pioneered the responsible application of genetics to clinical medicine over a 20-year career.