Aromatic L-Amino Acid Decarboxylase Deficiency

Medically Reviewed by Neha Pathak, MD on May 06, 2022
Written by Keri Wiginton
12 min read

AADC deficiency is an ultra-rare genetic disorder. It affects how your cells send signals to each other.

People born with this condition don’t make enough aromatic l-amino acid decarboxylase (AADC). That’s an enzyme that helps your brain and nervous system work. Babies and kids with AADC deficiency have developmental delays, weak muscle tone, and movement disorders. They can get other symptoms, too, like droopy eyelids, stiff muscles, and stomach problems.

AADC helps your body make serotonin and dopamine. These are "chemical messengers" called neurotransmitters. Without enough AADC, you don't have enough neurotransmitters to send signals through your nervous system. That makes it hard to control your body, especially your head, face, and neck. It can also affect things like your blood pressure, heart rate, and body temperature.

Signs of AADC deficiency occur early in your baby’s life. There isn’t a cure, but treatment might help manage their symptoms.

It’s OK to ask for help as you or your child deals with this lifelong condition. Tap into your health care team, friends, and family, or find others going through the same thing. A support network can be a big help.

Some people inherit genes with random changes, or mutations. You get AADC deficiency when that happens to your dopa decarboxylase (DDC) gene, which tells your body how to make AADC. You get a copy of the gene from both of your parents. But this disorder is recessive. That means the gene in each parent has to mutate for you to get AADC deficiency.

You’re called a carrier if you have only one copy of the DDC mutation. If you have a child with another carrier, here’s what happens:

  • There’s a 25% chance your child will have AADC deficiency.
  • There’s a 50% chance your child will be a carrier. They likely won’t have any symptoms.
  • There’s a 25% chance your child will have two unchanged copes of the DDC gene. They won’t have AADC deficiency, and won’t be a carrier either.

AADC deficiency is just as likely to show up in males and females. So far, it’s found most often in people of Chinese, Taiwanese, or Japanese descent, followed by people who are Caucasian. It's extremely rare. We know of about only 150 cases to date.

Signs of AADC deficiency are likely to show up when your baby is first born or a few months later. Some symptoms can be mild. Others are serious. Your child might have more symptoms later in the day or when they’re tired. Sleep may help them feel better.

Here are the most common symptoms:

Hypotonia. This is the medical term for weak muscle tone. Someone with AADC deficiency may not be able to hold up their head and torso on their own. Your baby might go limp when you hold them. Your doctor might call this floppiness.

Developmental delays. Your child might fall seriously behind on certain milestones. They might not walk or talk. If they do, those actions will happen a lot later than for other kids.

Oculogyric crises. These “spells” or “attacks” can last for seconds, minutes, or hours. They may happen several times a week. Stress and tiredness may trigger them.

When your child has an oculogyric crisis, they can get symptoms like:

  • Involuntary eye movements, like rolling the eyes upward
  • Serious crankiness or agitation
  • Pain
  • Muscle spasms
  • A tongue that sticks out

Other movement disorders. Your child’s muscles might move slowly (hypokinesia) or contract repeatedly (dystonia). Their arms and legs might stay in a fixed position for a while.

Gastrointestinal issues. Your child can have a number of digestion-related problems. They include:

  • Diarrhea
  • Constipation
  • Acid reflux
  • Feeding problems (in babies)
  • Trouble gaining weight
  • Low blood sugar (hypoglycemia)

Autonomic symptoms. AADC deficiency affects the part of your nervous system that controls unconscious bodily functions. You might have symptoms like:

  • Droopy eyelids
  • Small pupils
  • Excess sweating
  • Stuffy nose
  • Drooling
  • Unstable body temperature
  • Low blood pressure
  • Fainting
  • Heart rate problems
  • Sleeping problems
  • Cardiac arrest (when your heart suddenly stops working)

Behavioral problems. Some kids with AADC deficiency might cry a lot, seem depressed, or have trouble communicating.

Your doctor will ask about your child’s developmental history and give them a physical exam. Symptoms for AADC deficiency can seem like other conditions. That includes cerebral palsy, epilepsy, and other genetic disorders. Your doctor might run blood tests or look at your child’s brain with magnetic resonance imaging (MRI) to rule out other conditions.

If your doctor suspects AADC deficiency, your child will need two or more of these tests:

  • Spinal tap. A doctor will insert a needle between bones in their spine to get a sample of cerebrospinal fluid. That’s the liquid that surrounds your brain and spinal cord. If your child has AADC deficiency, certain chemicals or substances will be higher or lower.
  • Blood test. A lab technician will take their blood through a needle in their arm. They’ll check to see if they have less AADC enzyme activity in their blood.
  • 3-OMD test. Your doctor might check your child’s blood for high levels of a substance called 3-0-methyldopa (3-OMD). Sometimes they use a dried blood spot test. That means your child only gets a finger or heel prick.
  • Genetic testing. A lab technician will check their blood for changes in the DDC gene. This is usually used to confirm the diagnosis. As a parent and possible carrier, you may need a genetic test too.

By Kelly Heger

When our daughter Jillian was born 26 years ago, everything seemed absolutely fine. We were not even home for more than a day when I developed symptoms of an infection, so we headed right back to the hospital. That ended up saving Jillian’s life; my husband took her to show her off to the maternity ward nurses and mentioned offhandedly that she felt cold every time he kissed her, which led to a temperature check. Her temperature was so low they thought the thermometer was broken. It wasn’t; they called a code on her. Later they told us she was only about 3 hours from dying.

We were admitted to the hospital for a month, and they did what they called a “million-dollar workup.” But they found nothing and sent us home saying she was likely just premature. Back home, she was sleeping 23 hours a day and was floppy like a rag doll when awake. Around 3 months old, she started having frightening spells where her eyes would roll up into her head, her body would get stiff, her breathing would become rattly, and she would gag on her tongue and turn gray and purple. This would continue for hours.

I knew something was terribly wrong, but because our doctor didn’t see her spells, he told us Jillian was fine. But in my heart I knew something was off. Then one day Jillian had a significant episode (what we now know is an oculogyric crisis) and I called the nearby children’s hospital. They told us to come into the ER right away. And that’s when fate intervened again, because the doctor on call happened to have diagnosed the first case of AADC deficiency in the country 2 months prior. She gave us our diagnosis.

From that day forward, I was on a mission. My husband and I started a foundation, now called the AADC Family Network. Obviously, we wanted a cure, but we also raise money for research and advocate for awareness. We knew that the more people -- doctors included -- knew about AADC deficiency, the more likely they would be able to recognize it in other kids, diagnose it early, and improve those kids’ quality of life. In fact, I was so passionate about learning as much as I could and communicating more effectively with the doctors and nurses that I became a nurse myself.

The biggest thing you can do for your child with AADC deficiency is to love them and see them as a kid who can do anything. They still want to dance, they still want to sing, they still want to play. Try to do some sort of physical therapy with your child every day. Encourage them to lift their heads, to reach, to look into your eyes and smile. With knowledge and hope, you can ride the journey together. 

After an AADC deficiency diagnosis, you and your child will work with many different specialists. These may include:

Pediatrician. This is your child’s general doctor. They can watch over your child’s overall development and treat illnesses.

Pediatric neurologist. Because AADC deficiency affects the nervous system, one feature is neurological symptoms such as seizures or movement disorders. Pediatric neurologists help diagnose and treat these symptoms.

Geneticist. These doctors may be the ones who first diagnose your child with AADC deficiency with genetic testing. They can also help you understand the condition better.

Physical, occupational, or speech therapist. These therapists can help your child strengthen certain everyday movement skills. This can help them with development, help them communicate, and in some cases can also reduce pain. A speech therapist can help with swallowing disorders as well as speaking.

Gastroenterologist. The problems that AADC deficiency causes with your child’s nervous system can often affect their digestive system. Many children with AADC deficiency deal with constipation, diarrhea, reflux, and they may need a feeding tube to be sure they’re getting enough nutrition.

Behavioral specialist. The nerve issues of AADC deficiency can lead to lots of crying and crankiness in many children. A behavioral specialist can help with tools to regulate their emotions and better manage mood.

Sleep medicine doctor. If the symptoms of AADC deficiency are making it hard for your child to get regular sleep, you may need a sleep specialist. They can help treat any physical symptoms that are preventing good sleep.

Social worker. The care of a loved one with AADC deficiency means coordinating lots of moving parts – financial, logistical, and emotional. Social workers can help connect you with the resources you need as you manage your child’s treatment.

Write down everything you’re curious about before your appointment. That way, you don’t forget any key questions. Ask your doctor if you can record the conversation so you can listen to it later.

Some questions you might want to ask include:

  • What are all of the treatment options?
  • What side effects can the drugs that treat the condition cause?
  • Can I enroll my child in a clinical trial on gene therapy?
  • Will my child need long-term care?
  • What complications should I watch for?
  • What drugs should my child avoid?
  • What nonmedical treatment can help?
  • Is there a social worker on the medical care team?
  • Do I need genetic counseling?
  • How can I find an AADC deficiency specialist?

Your doctor will design a care plan just for your child. That’s because there isn’t one treatment that works for everyone. A mixed approach with medication and other kinds of therapy might help manage symptoms. More research is needed, but experts think people with AADC deficiency might respond better to drug treatment if they start before they’re 2 years old.

Treatment for AADC deficiency includes:

Dopamine agonists. These drugs raise the amount of dopamine in your nervous system.

MAO inhibitors. These lessen the breakdown of dopamine.

Pyridoxine (vitamin B6). It’s thought to help the AADC you do have work better.

Anticholinergic agents. The idea is that these drugs balance out your dopamine and acetylcholine, a chemical messenger in your brain. They might help ease symptoms like excess sweating, movement problems, and oculogyric crisis.

Melatonin. This is a natural chemical your body makes. Supplements might ease sleep problems.

Benzodiazepines. These quiet down your central nervous system. There’s some evidence that occasional use of them can lessen oculogyric crises or dystonia in some people.

Drugs for other symptoms. Your doctor might add medicines to help with your child’s specific symptoms, like a stuffy nose, crankiness, sleep problems, or muscle contractions.

Nondrug therapy. Depending on your child’s symptoms, they might need physical, occupational, or speech therapy.

Gene therapy. This is when doctors replace your nonworking gene with one that works the right way. This kind of treatment looks promising, but it’s not widely available. We need further research before more people with AADC deficiency can get it.

Make regular doctor visits. See a neurologist at least once a year. They should have experience with movement disorders or neurometabolic diseases that affect children.

Make an emergency card. People with AADC deficiency should always have certain information with them. That way, if they have a “spell,” people who are nearby can know how to help them safely.

You can include:

  • Info on what AADC deficiency is
  • Emergency contact numbers
  • Dangers to watch for
  • Drugs to avoid

Get vaccinated. Kids with AADC deficiency are more likely to get infections, and their bodies may not be able to fight them as they should. Your child and everyone else in your household should get vaccines.

AADC deficiency is so rare that scientists aren’t sure how it’ll develop in each person. Most of the time, it doesn’t get worse as your child gets older. But new symptoms, like joint issues, can show up because of movement problems caused by the condition.

Serious cases can cause life-threatening symptoms. Ask your doctor what to watch for so you know what to do in an emergency.

Your child will have a health care team that will provide treatment guidelines and work with your child to help manage the symptoms of their disease. But as a caregiver for a child with AADC deficiency, you’ll take on the vast majority of the day-to-day, hour-by-hour tasks of your child’s care.

It’s important to find support for yourself so you’re best equipped to support your child.

Just after diagnosis

There are many emotions surrounding a new and life-changing diagnosis. As you process, make sure you also:

  • Learn as much you can. The more informed you are about AADC deficiency, the more you’ll be prepared for what’s to come. Ask your health care team questions to make sure you understand not only the disease, but its treatment and outlook.
  • Build your team. You’ll be in close contact with your child’s doctor, so be sure you feel comfortable with them. Find doctors who know about AADC deficiency or who can work with doctors who do. Find out which specialists might be helpful for your child’s specific needs.
  • Find support groups. Though AADC deficiency is rare, there are groups dedicated to the condition that can connect you with other people living with and caring for someone with the disease. Visit the websites for the AADC Family Network, Pediatric Neurotransmitter Disease Association, and the U.K.-based AADC Research Trust for more information.

As the disease progresses

The care required for a child with AADC deficiency is lifelong. As you settle into a routine and your child ages, make sure you’ve built in healthy systems that support you as well.

  • Consider home care. Ask your doctor or social worker if there may be services to help equip you with medical care in your home on a regular basis so that you can maintain a job or better care for other children. 
  • Take breaks. Many children with a chronic disability qualify for home and community-based Medicaid waivers that cover the cost of respite care – services that will care for your child if you need to be away.
  • Make a long-term plan. Think through the future of caregiving for your child as they age. Consider who would be able to step in if something were to happen to you.

You might feel stunned when you learn your child has AADC deficiency. But you don’t have to handle the diagnosis alone. It often helps to connect with others who understand what you’re going through. You can find a support community that meets in person or online.

To find the right group, ask your doctor or social worker. They can put you in touch with a condition-specific or general support group. You can also look for resources on the websites of AADC Trust or RareConnect.

If you get overwhelmed, it’s OK to reach out to a mental health professional. Your doctor can help you find someone to talk to.

Although there is currently no cure for AADC deficiency, researchers are exploring new approaches to treating the disease. Since AADC deficiency is caused by a DDC gene mutation, most of the current trials and studies are focused on gene therapy. Through this therapy, researchers hope to introduce regular DDC genes into the body using a genetically engineered virus.

Viruses can insert genetic material into cells so that the cells will use their own replication process to churn out more of the virus. Researchers are working to develop a virus that has a working DDC gene. In clinical trials, researchers have injected these viruses into specific parts of the brain in kids with AADC deficiency. Studies are looking at whether this type of gene therapy could produce a more functional AADC enzyme in people in these trials. This therapy isn’t yet approved by the FDA, but the few results so far have been promising.

To learn more about ongoing clinical trials, visit the AADC Family Network Research page.