The symptoms of cerebral ALD are quite varied. They include: “spacing out” in school: inattention, deterioration in handwriting skills, and decreased school performance; difficulty in understanding speech (though sound perception is normal); difficulty in reading and understanding written material; clumsiness; visual disturbances and occasionally double vision; and aggressive or unexplained inappropriate behavior. In some boys, seizures may be the first symptom. Symptom severity varies from patient to patient and is not determined by phenotype. Even identical twins may have different experiences with symptom onset and severity.
Gradually, as the disease spreads throughout the brain, their symptoms grow worse, including blindness, deafness, seizures, loss of muscle control, and progressive dementia. This relentless downward spiral leads to a vegetative state or death usually within 2-5 years of diagnosis.

• Behavioral problems
• Hyperactivity
• Eye pain/Childhood onset migraines
• Recurring viral infections
• Lethargy, tires easily, clumsiness
• Hypoglycemia
• Tanning or bronzing of the skin
• Adrenal insufficiency
• Attention deficit disorder (ADD)

The diagnosis is made chiefly by MRI and visualizing white matter changes accompanied by contrast enhancement.

Once a boy is diagnosed with cerebral ALD, it is crucial to undergo prompt evaluation in order to evaluate eligibility for a hematopoietic stem cell transplant (HSCT). It is crucial for a boy to undergo bone marrow transplantation at the earliest signs of the disease. A “Loes Score” is a system used to distinguish how far advanced their ALD as seen on MRI. A “Loes Score” of less than 9 and closer to 1 has shown to have the most optimal results following HSCT. For a cord blood transplant, stem cells come from umbilical cords that are donated and stored after healthy births of unaffected donors. To learn more about donating your baby’s umbilical cord, please visit the Carolina Cord Blood Bank.

Bone Marrow Transplant
Once brain MRI changes are identified, evaluation for transplant is an option. Although this procedure has risks (infections, graft versus host disease, and other complications can be life threatening), outcomes depend on the child’s clinical status at the time of the evaluation, along with interpretation of the brain MRI.

Hematopoietic stem cells are special cells found in bone marrow that grow or mature into different types of cells. In allogenic stem cell transplantation, affected individuals, receive hematopoietic stem cells from a healthy person, referred to as the donor, cells to produce the protein that the patient with cerebral ALD is incapable of making. A series of studies conducted over the last two decades have shown that a HSCT stops the progression of neurological disease in ALD, although it does not improve adrenal insufficiency. The procedure aims to use the donor-derived HSCT can be lifesaving, but it is not a cure. It is not offered unless a boy has cerebral ALD. It is unclear if patients who undergo HSCT as a child may still develop AMN in adulthood.

bluebird bio, a company located in Cambridge, MA is developing a gene therapy product, Lenti-D, for the treatment of boys with cerebral ALD. Lenti-D gene therapy aims to genetically modify the boy’s own stem cells with healthy copies of the ABCD1 gene and use the modified cells for transplant. Since the boy’s own cells are used, the hope is that Lenti-D can provide the same effectiveness seen with bone marrow transplantation, but without the risk of rejection of GVHD that can occur when cells are used from someone else’s bone marrow or cord blood. Currently in a Phase 2/3 clinical trial, bluebird bio has reported successful outcomes.

The initial results were published in the New England Journal of Medicine and suggest that Lenti-D be a promising therapy for this devastating disease. As of February 2020, more than 40 boys have been treated by Lenti-D worldwide, some of them with more than 5 years of follow-up. The treatment is generally well tolerated and outcomes favorable. None of the boys experienced graft versus host disease (GVHD) or graft rejection.

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The Smith Family

I thought he had too much wax in his ears. That’s how this started, wax. My boys always have gross waxy ears, no matter how much I clean them. Pretty gross right? I thought Grady couldn’t hear me well because of waxy ears.

After about two weeks, I decided to bring Grady to his pediatrician. She checked and they were clear. We proceeded to do a hearing test. He passed. Gut punch #1.

His pediatrician suggested we follow up with ENT. I asked if it could be neurological. She didn’t think so, everything else was perfect. About an hour after we got home, she called me saying, “You are not an alarmist with the kids, let’s see an ENT today”.

She got us in, and he passed most of the exams. Gut punch #2. I knew something bad was coming. My husband and I took Grady to Boston Children’s Hospital right from the ENT. I felt like we had to push to really get them to listen. Neuro came and did a consult. Physically he checked out perfect. Then, the doctor asked, “What is 3×4…” Grady said, “Football”. Now we were crying. Something was really wrong.

They came back and said they felt he was fine to go home, and out came Mama Bear. We told them we did not feel comfortable bringing him home. Twice. We told them SOMETHING is wrong with our son. I begged to scan him then. Sobbing. They felt a scan could wait and would book it in the weeks to come. So, we went home. Sick to our stomachs. The next morning, I woke up, called the pediatrician, and told them that I was bringing Grady back to Children’s and I wasn’t leaving until they scanned him. Long story short, a few frustrating hours later, they did. Gut punch #3…….and the death of the “old me”. They told us that they believed Grady had ALD. What the hell is ALD?!? I Googled it, alone in the “quiet room” after an ER doctor told me not to. Google was obviously lying because there was no WAY my football and basketball obsessed boy was going to die in 1-5 years. Part of me died then.

We were referred to a neurological team specializing in ALD. With a Loes score of 10, our new team felt that perhaps Grady might lose some hearing, some vision, he might have a change in his gait. We could handle anything as long as he was with us. With newfound strength we got ready to fight. Admitted to the hospital on 9/11/18 and met what came to be some new “family” members (his loving nurses), chemo started the next day. Grady was a rockstar. Me, not so much – I dubbed myself “the neurotic mom in room 613” . He was transplanted 9/20/18.  Celebrated his 8th birthday on 10/2/18 and also started engrafting that same day. We were home 10/11/18.

We were trying to come to terms with some signs of ALD that presented post-transplant, like an Auditory Processing Disorder. Grady can hear us, but he struggles to understand language. Luckily – that’s his ONLY deficit. He is a miracle boy!

Other than not really looking like Grady from all the prednisone and stupid hairy cyclosporine, he is still the same Grady, but he is angry.  So angry, and rightfully so. Some days are better than others, but he is here and doing amazing. There is hope – so much hope.  This disease is awful, but if he has to have it, I’m glad to have found the people I have in this ALD community.