Aromatic amino acid decarboxylase deficiency

Synonyms

4

Overview

Aromatic l-amino acid decarboxylase (AADC) deficiency is an inherited condition that affects the way signals are passed between certain cells in the nervous system. In this disease in born error of metabolism involving the deficiency of an enzyme (aromatic L-amino acid decarboxylase) needed to process aromatic amino acids. This results in a deficiency of neurotransmitters such as dopamine and serotonin. The condition manifests as movement and neurological problems.

Symptoms

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). 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.

Causes

The condition is caused by mutations in the DDC gene. It is inherited in an autosomal recessive pattern. The DDC gene provides instructions for making the AADC enzyme, which is important in the nervous system. This enzyme helps produce dopamine and serotonin from other molecules. Dopamine and serotonin are neurotransmitters, which are chemical messengers that transmit signals between nerve cells, both in the brain and spinal cord (central nervous system) and in other parts of the body (peripheral nervous system).

Diagnosis

Genetic Testing Registry

Treatment

There is currently no cure for aromatic L-amino acid decarboxylase deficiency (AADC). Different medications can be used to help treat the signs and symptoms of AADC. However, although certain combinations of medications may help some children, the medications do not improve the signs and symptoms of AADC for many children. Since the nervous system in a child with AADC does not have enough of certain neurotransmitters (the special chemicals the nerve cells use to talk to each other), the goal of many of the treatments is to make certain as much of these neurotransmitters is availabe as possible.

Medication could include any one or combination of the following:

  • Dopamine receptor agonist
  • Anticholinergic agents
  • Seizure medication
  • Monoamine oxidase inhibitor
  • Serotonergic medications (work by keeping more serotonin available)
  • Gastrointestinal medications

Other recommended therapy include:

  • Physical therapy
  • Occupational therapy
  • Speech therapy

Although gene therapy treatment for AADC seems promising in animal models (mice with AADC), clinical studies in humans have not been completed to make sure the treatment works (effective) and is safe.

Resources

  • NIH
  • Genetics Home Reference