Speech delays may have a cause, genetic testing is recommended

The Allen family spent the first two years of their youngest son Lucas’ childhood searching for answers. Lucas was not making any sounds—no babbling or even crying. His parents noticed signs of low muscle tone and were concerned. They began seeking testing in 2018, and in 2019, when Lucas was two-years-old, the Allens finally received an answer. Lucas was diagnosed with a rare condition called Creatine Transporter Deficiency (CTD).

2021 marks the 20th anniversary of the discovery of Creatine Transporter Deficiency, one of the three known Cerebral Creatine Deficiency Syndromes (CCDS), and 20 long years without a cure for families with a loved one affected by CTD. The Allens learned that creatine, the compound essential for building a healthy brain and muscles for Lucas, was not being transported into their young son’s cells and that there was no treatment currently available to overcome this.

CTD robs their now three-year-old son of the ability to communicate with his family—to say things like “mama” and “dada,” to ride a bike, and to play with his big brother. The Allen family has adjusted to a new normal and cherish both of their sons. They are learning to write their own story. “Lucas means ‘bringer of light,’ and he has, without question, brought so much light and love into our family and to those dearest to us,” said his mother, Jennifer Allen.

Learning that Lucas has CTD carries the hope of brighter days ahead for the Allen family.

‘Quest for a diagnosis’

Lucas’ mother and father, Jennifer and Randy Allen, began noticing their second born was missing development milestones when he was about 8-months-old. At the time, he still wasn’t sitting on his own, often falling over, and had issues with low muscle tone, which made bowel movements and controlling his body difficult. At 15-months, he still wasn’t babbling. He wasn’t consistently responding to his name.

“This was when we knew we were on a quest for a diagnosis,” Randy said.

Like many parents of children with Cerebral Creatine Deficiency Syndromes (CCDS), the journey to a diagnosis is arduous. Faced with test after test, children with CCDS are often diagnosed with autism, global developmental delay, and almost always speech delay without getting to the genetic root cause of the condition. And while these diagnoses qualify them to receive much-needed physical, occupational, and speech therapies, it does not help in the long run to getting treatments for creatine deficiencies. Rare diseases, like Creatine Transporter Deficiency, often do not get the funding required for treatments because so few patients are affected. There are a few hundred CTD patients currently diagnosed in the world. However, researchers estimate that CTD is massively under-diagnosed and, if all these diagnoses were to come to light, the condition would receive more support for research into treatments.

In people with CTD, the body’s cells do not receive creatine, an essential amino acid needed to sustain the energy levels required for proper muscle and brain development. Though CTD does not have a treatment, the two other CCDS conditions, Guanidinoacetate Methyltransferase Deficiency (GAMT) and Arginine:glycine Amidinotransferase Deficiency (AGAT), do. The symptoms are very similar, but misdiagnoses for GAMT and AGAT are especially devastating because a treatment is available.

For Lucas, the myriad of tests began with auditory exams to rule out hearing issues, then behavioral and developmental assessments. Fragile X and comparative genomic hybridization genetic tests came back negative. Both parents also underwent genetic testing, and neither were identified as carriers for any unique conditions, including CTD.

The Allen family settled into their weekly therapy sessions. They hoped for progress; they hoped for improvement. Would Lucas speak today? Would their youngest son conquer another long-missed milestone?

“Lucas worked really hard in therapy, and we saw some results,” Jennifer said. “As his mother, I still felt like we were missing something.”

While an MRI was not deemed necessary for Lucas at the time, the family advocated for one.

“A gracious and committed colleague was very familiar with the health system at University of California San Francisco and helped us navigate our way in finding geneticist Dr. Joseph Shieh,” said Jennifer, adding that Shieh requested a magnetic resonance spectroscopy (MRS) scan also be conducted simultaneously with the upcoming MRI. The Allens are lucky because MRS is critical for diagnosing creatine deficiencies but it is rarely ordered, whether due to physician awareness or facility availability or even insurance policies.

The MRS scan showed a clear indicator of creatine deficiency (lack of a creatine peak) in Lucas’ brain that led to his CTD diagnosis. “So many things had to align for this to happen,” Jennifer explained. “If our appointment with Dr. Shieh was after our scheduled MRI, we may still not have a diagnosis.”

‘Believing in what’s possible’

Today, a day in Lucas’ life consists of therapies and four supplements, including creatine, three times a day. While tests show the creatine is still not being transported throughout his body as it should, Lucas’ gross motor skills have improved.

The Allen family’s goals for Lucas are simple. Like all moms and dads, they want to see their child grow strong, be given opportunities in life, and have meaningful relationships. But for families of children with CTD, there are challenges that most parents don't face, like potty training, transitioning out of a crib, and above all speech, like hearing the long-awaited “I love you.”

While most parents deter their children from jumping in the house, this simple act is one of Lucas’ latest milestones. “He is learning how to jump, which took about three months and outfitting our living room with a trampoline,” Jennifer explained. It’s a big leap toward progress and a win worth celebrating.

“Most of all,” Randy said, “we are thankful that he is happy and loved.”

The Allen family has received an “outpouring of love and support from our extended families and communities.”

“We will continue to strengthen our faith, as we believe that will be key in our success as a family while we wait for science to progress,” Randy said. “2021 will be focused more on the present, believing in what’s possible and being grateful for all the progress Lucas continues to make.”

The Allens understand that this is a rare disorder, which many pediatricians know very little about, and they recommend asking your pediatrician to screen for a creatine deficiency if they notice any of Lucas’ symptoms—especially speech delay, low muscle tone, or failure to thrive.

Since Lucas’ CTD diagnosis, the family now has peace of mind. “We know what it is, and we know directionally what we can do to help Lucas thrive,” Jennifer explains. “It allows us to focus on today and the future—of which we are optimistic. Scientific research, modern medicine, a strong community in ACD, a loving family, and the power of prayer offer us a ton of promise for a bright future for Lucas.” 

The Allen family has become active patient advocates and CCDS research supporters. They rallied in December to support the cause, asking friends and family to help support CCDS gene therapy research. The fundraiser brought in nearly $100,000, all of it going towards funding research into treatments. Randy has gone one step further and joined the Association for Creatine Deficiencies Board of Directors to take a hands-on approach to accelerating research.

“The amazing progress the world saw in developing a COVID vaccine in 2020 brings us hope. If we can bring together researchers, uniting their efforts towards a CTD treatment, I believe the future is promising,” says Randy.

For the family of the boy who is the “bringer of light,” there’s solace in knowing what you face and what you’ve been given. “Once you embrace that,” Randy said, “you get to learn the reason behind the gift and take advantage of the opportunity to open your heart to love in ways you never thought imaginable”.

The Association for Creatine Deficiencies is advocating for families, like Lucas’. More research is needed to discover a treatment—and cure—for CTD. The mission of the Association for Creatine Deficiencies (ACD) is to eliminate the challenges of Cerebral Creatine Deficiency Syndromes. The ACD is committed to providing patient, family and public education to advocate for early intervention through newborn screening and to promote and fund medical research for treatments and cures for cerebral creatine deficiency syndromes. For more information regarding creatine deficiencies, or to support the ACD’s mission, visit creatineinfo.org.