AADC Deficiency

aromatic l-amino acid decarboxylase deficiency

aadc dopamine deficiency
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Exhibited
Developmental Delay

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Variant
Phenotypes

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Cases
since 1990

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Months
Age of Onset

Neurotransmitter Disorder

Aromatic L-Amino Acid Decarboxylase Deficiency​

AADC deficiency is an ultra-rare genetic neurotransmitter disorder.  It is an inherited disorder that affects the way signals are passed between certain cells in the nervous system. People born with AADC deficiency don’t make enough an enzyme that helps your brain and nervous system work. 

AADC helps your body make serotonin and dopamine. These are “chemical messengers” called neurotransmitters. AADC deficiency patients 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.

About AADC deficiency

AADC Deficiency Symptoms

Signs and symptoms of AADC deficiency generally appear in the first year of life. 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.

Affected infants may have severe developmental delay, weak muscle tone (hypotonia), muscle stiffness, difficulty moving, and involuntary writhing movements of the limbs (athetosis). They may be lacking in energy (lethargic), feed poorly, startle easily, and have sleep disturbances. People with AADC deficiency may also experience episodes called oculogyric crises that involve abnormal rotation of the eyeballs; extreme irritability and agitation; and pain, muscle spasms, and uncontrolled movements, especially of the head and neck.

AADC deficiency may affect the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. Resulting signs and symptoms can include droopy eyelids (ptosis), constriction of the pupils of the eyes (miosis), inappropriate or impaired sweating, nasal congestion, drooling, reduced ability to control body temperature, low blood pressure (hypotension), backflow of acidic stomach contents into the esophagus (gastroesophageal reflux), low blood sugar (hypoglycemia), fainting (syncope), and cardiac arrest.

Signs and symptoms of AADC deficiency tend to worsen late in the day or when the individual is tired, and improve after sleep.

ADDC Deficiency

Causes

AADC Deficiency Diagnosis

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.

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AADC Deficiency Treatments

Existing treatment approaches can help manage symptoms of AADC deficiency, but they do not address the underlying genetic cause of the disorder. These treatments have not been approved to treat AADC deficiency specifically, but they may help with certain symptoms.

View the paper “Consensus guideline for the diagnosis and treatment of aromatic l-amino acid decarboxylase (AADC) deficiency” written by representatives of the International Working Group on Neurotransmitter Related Disorders (iNTD) and published in the Orphanet Journal of Rare Diseases, which outlines key symptoms as well as recommended strategies for the diagnosis and management of AADC deficiency.

The only treatment that offers promise and results is gene therapy. The gene therapy Upstaza (eladocagene exuparvovec) has been approved in the U.K and across 27 member states of the European Union, as well as Iceland, Norway, and Liechtenstein to treat adults and children, 18 months and older, with aromatic l-amino acid decarboxylase (AADC) deficiency.

Vitamin B6 (pyridoxine)

The first treatment for patients with AADC deficiency is vitamin B6, also called pyridoxine. Vitamin B6 acts as a cofactor of the AADC enzyme — in cases where patients have small amounts of functional AADC enzyme, this treatment can increase the activity of the enzyme that is present. However, several case studies have indicated that this treatment leads to only limited improvements in AADC deficiency patients.

Dopamine receptor agonists

Dopamine receptor agonists are compounds that bind to dopamine receptors in the brain, activating the receptors. In some conditions, dopamine receptor agonists can compensate for a decrease in dopamine in the brain. While no dopamine receptor agonists have been approved to treat AADC deficiency, this type of medication has been used off-label for this disease. Dopamine receptor agonists include bromocriptine, rotigotine, and aripiprazole, among others.

Monoamine oxidase inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) are a class of medications that inhibit MAO, the enzyme that breaks down serotonin and dopamine. They, therefore, act to increase the amount of dopamine and serotonin in the brain. Even though MAOIs have not been approved to treat AADC deficiency, they have been prescribed off-label to treat some AADC patients. However, there is limited evidence that MAOIs are effective in treating the symptoms of AADC deficiency.

Gene Therapy

Several companies (including PTC Therapeutics) are developing gene therapies to treat AADC deficiency. This type of experimental treatment uses a virus to introduce a corrected version of the DDC gene into nerve cells so that they can produce normal AADC enzyme.

Have questions?

AADC Deficiency Frequently Asked Questions

Signs and symptoms of AADC deficiency generally appear in the first year of life. Affected infants may have severe developmental delay, weak muscle tone (hypotonia), muscle stiffness, difficulty moving, and involuntary writhing movements of the limbs (athetosis).

AADC deficiency is caused by mutations (changes) in a gene called DDC (which stands for DOPA decarboxylase, another name for AADC). An abnormal DDC gene leads to production of a dysfunctional AADC enzyme that cannot accomplish its normal functions.

Nobody knows the life expectancy of a child living with AADC deficiency. Symptoms vary greatly from child to child, and because there are so few children currently diagnosed with the disorder, it is impossible to say what the long-term effect of AADC deficiency will be. However, many children die at an early age due to complications resulting from the debilitating symptoms.

Pediatric neurologists usually treat patients with AADC deficiency 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. You can contact doctors who specialize in the disease online for telehealth consultations.

Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare, autosomal recessive neurometabolic disorder, with an estimated prevalence of between 1:64,000 and 1:90,000 births in the USA, 1:116,000 in the European Union, 1:162,000 in Japan and 1:32,000 in Taiwan. The true number may be much higher since many patients go misdiagnosed or undiagnosed.

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