Aromatic L-amino Acid Decarboxylase (AADC) deficiency

Receiving a diagnosis of aromatic L-amino acid decarboxylase (AADC) deficiency may leave you with many questions and concerns. If you know or care for someone who has recently been diagnosed with AADC deficiency, you may be looking for information on how best to support them.

We have created a list of frequently asked questions around AADC deficiency to support you and those you care for in understanding their diagnosis.

What is AADC deficiency?

Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare, autosomal recessive neurometabolic disorder that leads to a severe combined deficiency of serotonin, dopamine, norepinephrine and epinephrine. Onset is early in life, and key clinical symptoms are hypotonia, movement disorders (oculogyric crisis, dystonia, and hypokinesia), developmental delay, and autonomic symptoms.

What causes AADC deficiency?

AADC deficiency is an inherited condition, autosomal recessive. This means both the mother and father have to pass on a ‘mutated’, or altered, copy of a certain gene. This gene is called dopa decarboxylase, or DDC. A person with two mutated DDC genes will have AADC deficiency.

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Autosomal recessive inheritance

 

What does the DDC gene do in the body?

The DDC gene is needed to produce an enzyme called AADC. Enzymes are proteins used by the body to help speed up chemical reactions. Mutations in the DDC gene mean that the body can only produce a small amount of the AADC enzyme.

Without the AADC enzyme, the body is unable to produce natural chemicals called neurotransmitters; examples include serotonin and dopamine. These chemicals act as messengers between cells in the nervous system that help control many of the body’s functions, including behaviour, learning new skills, and movement.

What are the symptoms of AADC deficiency?

The symptoms of AADC deficiency can vary from person to person. Most children who have the condition show symptoms in the first few months of life.

The most common symptoms include:

  • Low muscle tone, sometimes called hypotonia or ‘floppy baby’ 
  • Delays in normal childhood development, such as not being able to lift and control the head, sit or stand without support, or speak
  • Increased tightness in muscles and difficulty in stretching muscles, sometimes called hypertonia
  • Problems with movement, such as involuntary muscle contractions called dystonia and involuntary eye movements called oculogyric crises OGC.

Oculogyric crises are often seen in people with AADC deficiency. During an episode, the eyes suddenly roll upwards involuntarily.These episodes can last from a few seconds to hours and can happen several times a day or several times a week. Involuntary movements, such as contracting muscles and/or twisting, may occur at the same time.

A person with AADC deficiency may also experience other symptoms and features, such as:

  • Drooling
  • A stuffy or runny nose
  • Irritability
  • Problems with digestion
  • Sleep disturbances
  • Excessive sweating
  • Feeding difficulties
  • Autism-like symptoms

It is important to remember that not every person will experience the same symptoms in the same way.

How is AADC deficiency diagnosed?

AADC deficiency can be diagnosed by carrying out three core tests:

  • A genetic test to identify changes in the DDC gene
  • A blood test to identify if there are low levels of the AADC enzyme
  • An analysis of spinal fluid to measure the levels of chemicals involved in the production of neurotransmitters

A positive result in both the genetic test and one of the other two tests above is needed to confirm a diagnosis.

Why can receiving an AADC deficiency diagnosis take so long?

Children with AADC deficiency are often diagnosed several years after their symptoms first start. AADC deficiency is rare, and its symptoms can be similar to those seen in other disorders. This makes it difficult for doctors to confirm a diagnosis. AADC deficiency can present with signs and symptoms that may be similar to those found in:

  • Cerebral palsy
  • Epilepsy
  • Behavioural disorders/autism

However, there are clues for doctors to consider AADC deficiency from other disorders. These may include:

  • Looking for involuntary eye movements (oculogyric crises)
  • Examining findings from a brain scan (called magnetic resonance imaging, or MRI) to exclude other conditions such as cerebral palsy
  • Identifying symptoms associated with how the body functions, such as excessive sweating, droopy eyelids, and a stuffy or runny nose
  • Noticing patterns of symptoms which may worsen throughout the day and improve with sleep

It is important that AADC deficiency is diagnosed early. This can help improve the care and support patients receive in managing the condition.

How is AADC deficiency managed?

To treat the symptoms of AADC deficiency, several different medications can be given. In general, the first treatments given for the disorder are:

  • Dopamine agonists which copy the actions of dopamine in the brain
  • Inhibitors of monoamine oxidase to increase levels of dopamine and serotonin in the brain
  • Pyridoxine, or vitamin B6, to increase the action of the AADC enzyme

Managing patients with AADC deficiency requires input from several specialties, known as a multidisciplinary approach. In addition to the paediatric neurologist, a patient with AADC deficiency may see the following specialties:

  • Physiotherapist
  • Speech therapist
  • Dietician
  • Psychologist

If you think your child or someone you care for may have AADC deficiency, speak to their doctor about your concerns.

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