Aromatic L-amino Acid Decarboxylase Deficiency

Patients and Parents

Home Patients and Parents Know Your Conditions Aromatic L-amino Acid Decarboxylase Deficiency

Introduction

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare neurotransmitter disease, which is a type of neurometabolic disorders.

Neurotransmitters, such as the catecholamines (dopamine, norepinephrine, and epinephrine) and the indoleamines (serotonin and melatonin) are chemical messengers which alter the signal transmission between neurons in the brain. They are involved in central brain functions, including the control of movements and behaviours, neuronal excitation and inhibition, regulation of body temperature and a lot of other processes.

Inherited deficiencies of neurotransmitters encompass defects of neurotransmitter synthesis and break down, as well as defects of neurotransmitter transporters. This results in a wide variety of clinical signs and symptoms which are typically complex, including motor, behavioural, cognitive, and autonomic involvements. Patients with AADC deficiency are at a high risk of death in the first decade of life.

Causes

Aromatic L-amino acid decarboxylase (AADC enzyme) is the final enzyme in the biosynthesis of the monoamine neurotransmitters serotonin and dopamine, and dopamine is the precursor for norepinephrine and epinephrine.

AADC deficiency is caused by genetic changes in the DDC gene that leads to the production of a dysfunctional AADC enzyme that cannot accomplish its normal functions.

Prevalence

The worldwide incidence of AADC deficiency is not known. AADC deficiency is thought to be more prevalent in certain populations that originate from Asia, particularly Taiwan, Japan, and China, due to a founder pathogenic variant (c.714+4A>T). A founder variant is a genetic alteration observed in a specific population (usually more geographically or culturally isolated) where one or more of the ancestors was a carrier of the altered gene. The estimated prevalence is 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.

Mode of Inheritance

AADC deficiency is inherited in an autosomal recessive manner, which means inheriting both copies of faulty genes, one from each asymptomatic parent who usually does not have the condition.

Signs and Symptoms

Individuals with AADC deficiency typically have complex symptoms, including motor, behavioural, cognitive, and autonomic findings.

Affected individuals can appear normal at birth. Symptom onset is in early infancy, typically within the first six months of life.

The most common non-specific initial symptoms include feeding difficulties, hypotonia, and developmental delay
More specific symptoms include:

Oculogyric crises (an acute dystonic reaction of the face and or eyes) which occur in most affected individuals, typically starting in infancy. These crises are characterized by intermittent or sustained eye deviation, usually upward or to the side, which may be accompanied by involuntary movements of the face, trunk, and / or limbs. Mild episodes may last for several minutes and involve the eyes only. Severe episodes may last for many hours, and may include whole-body dystonic posturing, breathing difficulty and sweating. Oculogyric crises occur in more than 90% of people with AADC deficiency and typically begin within the first six months of life. They tend to recur every two to five days.
Movement disorders (especially dystonia)
Autonomic dysfunction (excessive sweating, unstable temperature, ptosis, nasal congestion, hypoglycaemic episodes)

Other common symptoms:

Sleep disturbance which can include insomnia and / or excessive sleepiness
Mood disturbance including irritability and anxiety

Seizures are an uncommon finding, occurring in fewer than 5% of affected individuals

For children with unexplained hypotonia, movement disorders (especially oculogyric crisis), developmental delay and autonomic symptoms, AADC deficiency should be considered.

Diagnosis

General

A complete clinical evaluation and a high index of suspicion are required to make the diagnosis. Your doctor will examine your child to look for signs and symptoms of AADC deficiency.

Looking for potential biomarkers for AADC deficiency through blood, urine and / or cerebrospinal fluid analyses
Establishing a definitive molecular diagnosis through genetic test

Special tests / investigations available in HKCH

The HKCH Neurology team provides assessment, counselling, diagnostic workup, and treatment for children suspected with AADC deficiency and other neurotransmitter related disorders.
Special diagnostic and biochemical tests including cerebrospinal fluid for neurotransmitter studies, targeted gene sequencing and next generation sequencing are available in HKCH.

Management and Follow-up

General

Continuous surveillance and evaluations of the signs and symptoms will be conducted to assess the extent of the disease and individual needs, improve quality of life, maximize function, and reduce complications for patients diagnosed with AADC deficiency. This ideally involves multidisciplinary care by specialists in relevant fields.
People with AADC deficiency can benefit from non-drug treatments, such as physiotherapy, occupational therapy and speech therapy in which trained specialists work with patients to improve their physical functioning.
Medication is available to manage the symptoms, though the response to treatment greatly varies among affected individuals and it can be difficult to achieve an optimal treatment regimen.
The gene therapy eladocagene exuparvovec has been approved in the European Union and United Kingdom for individuals aged 18 months and older who are diagnosed with severe AADC deficiency (confirmed clinically, biochemically and genetically). This treatment was also approved by the FDA in November 2024 for use in the United States.
It is important to attend the nearby accident and emergency department (A&E) immediately for timely in-hospital support and monitoring, in case of any medical emergency. A letter or information sheet on the emergency management of AADC deficiency is a helpful quick reference for presenting to the A&E or other healthcare professionals in case they have not encountered AADC deficiency before.
Agents / circumstances to avoid:
- Centrally acting dopamine antagonists should be avoided in patients with AADC deficiency. Metoclopramide should not be used for the treatment of nausea.
- In case of nausea and vomiting, supportive care to avoid dehydration and hypoglycaemia is most important. If possible, anti-dopaminergic and anti-serotonergic agents should be avoided. If medical therapy is needed, low dose domperidone can be considered.

Special management and follow up-available in HKCH

HKCH manages patients with AADC deficiency and its associated medical problems with a holistic and multidisciplinary care model.

The multidisciplinary neurology team comprises of paediatricians, geneticists, biochemical pathologists, nurses, dietitians, pharmacists, physiotherapists, occupational therapists, speech therapists, clinical psychologists and medical social workers. The management is further enhanced through collaboration with various paediatric sub-specialties.

We offer inpatient, day patient, and outpatient assessment and follow-up for patients, as well as tele-support for regional hospitals, clinics, and families. Carers and patients are educated and empowered for home management, whilst staying in contact with the team for advice and support.

References and Useful Information

Acknowledgement

Principal author: Dr Sheila Wong on behalf of Neurology Team, HKCH

Initial posting: Nov 2025