Aromatic L-amino acid decarboxylase deficiency (NORD)
Definitions & Key takeaways
Aromatic L-amino acid decarboxylase deficiency (AADC) is an autosomal recessive disorder caused by mutations in the Dopa Decarboxylase (DDC) gene. AADC is an enzyme involved in the synthesis of dopamine and serotonin, which are important neurotransmitters responsible for the communication among neurons. This condition is characterized by impaired cognitive development, decreased muscle tone, failure to thrive, abnormal eye movements, and a wide range of other neurologic symptoms.
Aromatic L-Amino Acid Decarboxylase deficiency, or simply AADC deficiency, is a very rare disease in which there’s a decreased activity of an enzyme called aromatic l-amino acid decarboxylase, or AADC for short.
The disease affects babies, which most often seem healthy at birth, but then start developing signs and symptoms during the first months of life.
The severity of the disease can vary between individuals. AADC deficiency mainly causes movement disorders.
One of the most frequent symptoms is hypotonia of the trunk, which means these individuals have very little muscle tone, making them floppy.
Another frequent symptom is oculogyric crises, which is the abnormal rotation of the eyeballs with elevation of the gaze, as well as uncontrolled movements of the head and neck, agitation, and irritability.
Oculogyric crises can last for hours, and typically occur every 2 to 5 days. Other less frequent movement disorders include decreased movement called hypokinesia, increased muscle tone of the limbs or hypertonia, and involuntary movements like tremors, twisting movements called dystonia, writhing movements or athetosis, dance-like movements of hands and feet called chorea.
AADC deficiency can also affect the autonomic nervous system, which is the part of the nervous system that controls our internal organs.
Symptoms can include excessive salivation and sweating, droopy eyelids called ptosis, nasal congestion, unstable body temperature, low blood pressure, and low blood sugar or hypoglycemia.
In addition, AADC deficiency can cause gastrointestinal symptoms like reflux, diarrhea, or constipation. Other less frequent symptoms include seizures, decreased or increased sleep, and decreased or increased reflexes.
Finally, children affected with AADC deficiency often have learning disabilities, developmental delay, and fail to reach milestones like talking or walking.
In addition, they may present feeding difficulties, leading to decreased growth. Moreover, these individuals are more likely to have medical complications, such as reacting inappropriately to surgery.
As a consequence, many children with severe disease don’t live through childhood. The cause of AADC deficiency is mutations in the DDC gene, which encodes for the enzyme AADC.
Now, AADC deficiency is an autosomal recessive disease. This means that, in order to have the disease, an individual must inherit two mutated genes, one from each parent.
Normally, the enzyme AADC is involved in the production of neurotransmitters, which are molecules that our neurons use to communicate.
Now, with AADC deficiency, very few neurotransmitters end up being produced. As a result, their signals and activities don’t work properly.
Now, the main neurotransmitters involved in AADC deficiency include dopamine, serotonin, epinephrine and norepinephrine.
Finally, epinephrine and norepinephrine are involved in regulating the autonomic nervous system. Diagnosis is based on patient history, as well as complete physical examination to assess the signs and symptoms of the disease, such as movement disorders and developmental delay.
Blood tests can be done to measure the activity of the AADC enzyme, which will be reduced in individuals affected. Next, a lumbar puncture can be done by placing a needle in the spinal column of the patient to collect cerebrospinal fluid.
In affected individuals, the cerebrospinal fluid will show low levels of neurotransmitters. Finally, genetic testing can be done to look for the mutated DDC genes and confirm the diagnosis.
Recently, a metabolite called 3OMD has been identified, which is specific and elevated in AADC deficiency. This may be used in the future to test for AADC deficiency on a dried blood spot obtained through newborn screening.
Currently, there's no cure for AADC deficiency, but there are some treatment options to help control the symptoms. Since severity can vary among individuals, the choice of treatment should be personalized.
Treatment options include medications like dopamine agonists to increase the dopamine levels, as well as monoamine oxidase inhibitors, which stop the enzyme monoamine oxidase from destroying neurotransmitters.
Vitamin B6 or pyridoxine can be given as a medication to help increase the activity of the AADC enzyme. Other medications can include melatonin to help with sleep problems, and benzodiazepines or anticholinergic medications to help with movement disorders.
In addition to medical treatment, individuals with AADC deficiency can benefit from a multidisciplinary approach that includes physical therapy, speech therapy, and psychotherapy.
Finally, clinical trials have shown potential in treating AADC deficiency with gene therapy, which aims to replace the mutated DDC gene with a functional gene.
##Summary All right, as a quick recap… Aromatic L-Amino Acid Decarboxylase deficiency is a very rare autosomal recessive disease in which there’s a decreased activity of the enzyme aromatic l-amino acid decarboxylase.
Symptoms can include hypotonia, oculogyric crises, developmental delay, decreased growth, and disruption of the autonomic nervous system.
Diagnosis is based on patient history, complete physical examination, blood tests, lumbar puncture, and genetic testing.
There is no cure for AADC deficiency, but there are some treatment options to help control the symptoms, as well as a multidisciplinary approach including physical therapy, speech therapy, and psychotherapy.
Finally, clinical trials of gene therapy
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