by Nancy Humphrey
Theodore Gray was born on May 13, 2021, a few weeks early — small, but seemingly healthy. His parents, Amanda and Coty, soon took him home to Waverly, Tennessee, to join big brother Tony, 7, who had prayed for a little brother.
The following week, Amanda was notified from Tennessee’s newborn screening program of the possibility that Theodore had adrenoleukodystrophy (ALD), a genetic condition occurring in about one in 17,000 people that over time damages the myelin sheath, the protective membrane that insulates nerve cells in the brain. Without the myelin sheath, the nerve cells that allow thinking, talking and controlling muscles no longer function correctly. The week after Amanda was alerted of the possibility, it was confirmed.
Newborn screening detects rare and possibly life-threatening disease that wouldn’t be immediately obvious. Symptoms could be years away. Early detection of ALD and other diseases that have effective interventions can prevent long-term complications or even be life-saving. Newborn screening is a simple blood test that is done before the newborn leaves the hospital, and involves about six drops of blood taken from the heel. The sample is tested for 69 diseases in Tennessee, including ALD, which was added to the screen in 2018.
Monroe Carell Jr. Children’s Hospital at Vanderbilt has established clinics for children with ALD and other genetic disorders that are found on newborn screening, including Fabry disease, Krabbe disease and others.
About three weeks after receiving the diagnosis from their pediatrician, the Grays met with Kevin Ess, MD, PhD, associate professor of Pediatrics, director of the Division of Pediatric Neurology and the Gerald M. Fenichel Professor of Neurology, during their genetic counseling at Children’s Hospital, then in July at a dedicated ALD clinic. This multidisciplinary clinic is a collaboration within Pediatrics between Neurology, Endocrinology, Genetics and Hematology/Oncology.
The providers participating in the multidisciplinary clinic include Ess from Neurology, Allison Shields, CPNP, MSN, from Genetics; Nidhi Gupta, MD, assistant professor of Pediatrics, from Endocrinology; and Jim Connelly, MD, assistant professor of Pediatrics, from Hematology/Oncology.
“They explained everything on a level we were able to understand,” Amanda said. “I’m in the medical field, but at a lab doing bloodwork, so anything dealing with neurology is so far above our heads. They took our questions, explained everything and gave us hope. If you Google any kind of leukodystrophy, it’s terrifying. The statistics are horrible. To have this team of specialists look at your child and say there’s hope here, that’s comforting.”
With ALD the body can’t break down very long-chain fatty acids (VLCFAs) causing saturated VLCFAs to build up in the brain, nervous system and adrenal glands. The most common type of ALD is cerebral X-linked ALD, which is caused by a mutation of the ABCD1 gene on the X chromosome. Cerebral X-linked ALD affects males much more severely than females, who can carry the disease without any symptoms.
Symptoms from this form of Cerebral X-linked ALD usually appear between ages 4 and 10 years. The white matter of the brain is progressively damaged (leukodystrophy), and symptoms worsen over time. Seemingly normal, healthy boys can begin to regress, at first showing minor behavioral problems like withdrawing or difficulty concentrating, then developing vision problems and coordination issues.
Gradually, because the disease spreads throughout the brain, the symptoms will grow worse — and could include blindness, deafness, seizures, loss of muscle control and progressive dementia. If not diagnosed early, childhood-onset cerebral ALD will likely lead to death within five to 10 years. There is hope, however, that bone marrow transplants done by Connelly and his team can prevent many of the neurological issues with these patients.
“For many of these rare diseases, a lot of our patients are driving from far away,” said Elizabeth Hinkley, a clinical research coordinator who coordinates the clinics. “Just organizing an annual visit can be complicated when you’re seeing multiple specialists. The purpose of the clinics are to streamline care; to make it easier for our patients with these rare diseases so when they come in, they can see almost all of their providers in one visit instead of having to come in three to four times to see different people.”
Amanda Gray and her family recently moved to Houston after an Aug. 21 flood destroyed their Waverly home. They will begin seeing a neurologist recommended by Ess at an existing ALD clinic at Texas Children’s Hospital.
Theodore is on no medications at this time since he is showing no symptoms. He has regular lab work done to monitor for adrenal insufficiency, which is something that he has a higher chance of due to ALD.
“He’s learning to roll over, laughs and throws his pacifier at people,” Amanda said. “He’s the absolute light of his brother’s life. Tony is so proud to be a big brother. When we brought Theodore home, he was under 5 pounds. It was like bringing home a doll. But now he’s so fat he doesn’t even look like he has a neck,” she says, laughing.
For more information about ALD and other rare disease clinics, visit https://www.vumc.org/rarediseases/welcome-vanderbilts-pediatric-rare-disease-center.