Aromatic l‑amino acid decarboxylase deficiency

A rare inherited disorder that impairs neurotransmitter production, leading to developmental delays, movement disorders, and autonomic dysfunction.

Overview

Aromatic l‑amino acid decarboxylase (AADC) deficiency is an inherited disorder that affects the way nerve cells (neurons) transmit information to other cells.

Signs and Symptoms

Signs and symptoms typically appear in the first six months of life. Affected infants may have feeding problems, weak muscle tone (hypotonia), and sleep disturbances. Most children experience episodes called oculogyric crises involving involuntary upward‑rolling movements of the eyes. Additional signs include developmental delays and intellectual disabilities.

Movement disorders are common. Involuntary movements such as muscle contractions that cause unusual body positions (dystonia) and writhing movements of the limbs (athetosis) may occur. Dystonia tends to worsen when tired but usually improves after sleep. Slow or diminished movements (hypokinesia) may also be present.

AADC deficiency can affect the autonomic nervous system, leading to droopy eyelids (ptosis), constriction of the pupils (miosis), inappropriate or impaired sweating, nasal congestion, drooling, poor control of body temperature, low blood pressure (hypotension), low blood glucose (hypoglycemia), and abnormal heart rhythms.

People with AADC deficiency have an increased risk of infection, which can lead to life‑threatening complications.

Frequency

AADC deficiency is a rare disorder. Approximately 350 people with this condition have been reported in the literature. The condition is more prevalent in certain Asian populations, particularly among people from Taiwan, Japan, and China.

Causes

Variants (also called mutations) in the DDC gene cause AADC deficiency. The DDC gene provides instructions for making the AADC enzyme, which plays an important role in the nervous system. Within neurons, the AADC enzyme helps produce dopamine and serotonin, two types of neurotransmitters. Neurotransmitters are chemical messengers that transmit signals to other cells in the body. Dopamine can be used to create additional neurotransmitters called epinephrine and norepinephrine.

Variants in the DDC gene can reduce the activity of the AADC enzyme. This causes neurons to produce less dopamine and serotonin than normal, which in turn