In the majority of patients with aromatic L-amino acid decarboxylase (AADC) deficiency, the disorder’s signs and symptoms are severe, with development delays, abnormal eye movements, sleep problems, diminished motor abilities, and sometimes emotional and mood problems common. However, comparatively milder disease courses also have been reported, and there is substantial variability among individual patients.
The genetic disorder is caused by mutations in the DDC gene that lower the activity of the AADC enzyme. This enzyme plays an important role in producing neurotransmitters such as dopamine and serotonin, which nerve cells use to communicate with each other.
A deficiency in these neurotransmitters, as well as in the dopamine-derived neurotransmitters neuroepinephrine and epinephrine, leads to poor communication between the brain and the rest of the body, which is what ultimately causes the disease’s symptoms.
The following are the most common symptoms of this rare disease.
Most children with AADC deficiency will have severe developmental delay; they will hit milestones like learning to sit up, crawl, talk, or walk at much later ages than normal.
Many patients never hit these milestones, and will only ever have minimal ability to move or talk on their own.
Babies with AADC deficiency often lack energy, feed and sleep poorly, and startle easily.
The problems with nerve cell communication that characterize AADC deficiency can impair the processes that normally govern movement, which may give rise to a range of movement-related disorders. Some of the most common movement disorders in AADC deficiency are described below.
Almost everyone with AADC deficiency experiences oculogyric crises, which are abnormal eye movements in which the gaze is involuntarily fixed in a certain position, usually upward, due to spasms in the muscles that control eye movement.
During crises, patients may be unable to close their mouths, and often their tongues stick out. Oculogyric crises may be accompanied by abnormal, uncontrolled, or restrictive movements in the neck, trunk, and/or arms and legs. These crises may last from seconds to hours.
Hypokinesia, or diminished motor activity, also is common among people with AADC deficiency. Notably, hypokinesia is different than paralysis, in which decreased muscle strength impairs movement. Instead, hypokinesia is characterized by overall fewer and smaller movements due to neurological disruptions.
Bradykinesia, an abnormal slowness of movement, also is common in people with AADC deficiency.
Atypical movements and abnormal muscle tone
Dystonia, another common motor manifestation of AADC deficiency, is characterized by involuntary muscle tensing or contracting, resulting in twisting motions, unusual postures, or slow and repetitive movements. This muscle tensing can be painful.
Some people with AADC deficiency experience myoclonus, which refers to an involuntary muscle jerk — a hiccup is a common example. Patients also may experience tremors, or uncontrolled shaking.
Seizures also may occur among some patients, due to sudden changes in electrical activity in the brain. These episodes often appear similar to dystonia or myoclonus, but the underlying cause is different. Medical tests can usually distinguish between these types of disorders.
Many people with AADC deficiency have abnormal muscle tone. Patients almost always have hypotonia, or low muscle tone, in muscles of the trunk, which may be accompanied by hypertonia —high muscle tone — in the limbs.
The autonomic nervous system is responsible for controlling involuntary bodily processes, such as breathing, digestion, and blood pressure. People with AADC deficiency often experience symptoms resulting from the abnormal function of the autonomic system.
The most common symptoms of autonomic dysfunction in AADC deficiency include drooping eyelids (ptosis), excessive sweating, and nasal congestion. Other common symptoms include excessive drooling, low blood pressure, abnormal heart rhythms, and diarrhea.
Some people with AADC deficiency experience problems with sleep, which may include difficulty sleeping (insomnia) and/or sleeping an excessive amount of time (hypersomnia). It is common for people with AADC deficiency to experience substantial fatigue.
Patients also may experience sleep apnea, when breathing intermittently stops during sleep, which can be deadly if not managed appropriately.
Mental health and behavioral challenges
The combination of nervous system problems and the stresses of living with a chronic illness can result in emotional problems and mood disorders, such as anxiety or depression. Some people with AADC deficiency experience dysphoria, which is a generalized feeling of unhappiness without a clear source, or abnormal irritability.
Children with AADC deficiency often cry excessively in early childhood, and autistic features may become apparent as children age.
Last updated: Jan. 10, 2022, by Marisa Wexler MS
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