Aromatic L-amino acid decarboxylase deficiency

Title

Other Names:

Aromatic amino acid decarboxylase deficiency; AADC deficiency; DDC deficiency; Aromatic amino acid decarboxylase deficiency; AADC deficiency; DDC deficiency; Dopa decarboxylase deficiency See More

Categories:

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders; Congenital and Genetic Diseases; Eye diseases; Metabolic disorders; Nervous System Diseases See More

Summary Summary

Aromatic l-amino acid decarboxylase (AADC) deficiency is a disease that affects the production of signals that allow cells in the nervous system to communicate with each other. These signals are called neurotransmitters. When the neurotransmitters are not being produced correctly, there are problems with the nervous system.^[1] Individuals affected by this disease often have trouble coordinating movements, especially of the head, face, and neck. Other symptoms of the condition include problems controlling blood pressure, heart rate, and body temperature.^[2]

AADC deficiency is caused by mutations in the DDC gene. The disease is inherited in an autosomal recessive manner.^[1] Diagnosis of the disease may be established based on a spinal tap and a blood test that show abnormalities in levels of neurotransmitters and enzymes related to the disorder. Genetic testing may be used to confirm the diagnosis.^[2] Treatment of the disease may include a variety of medications which may result in varying levels of success in individual patients. Physical, occupational, and speech therapy may also be of benefit.^[2]

Last updated: 7/14/2017

Symptoms Symptoms

Symptoms of aromatic l-amino acid decarboxylase (AADC) deficiency typically present during the first year of life. Symptoms may include severe delay in reaching milestones such as walking and talking (developmental delay), weak muscle tone (hypotonia), muscle stiffness, difficulty moving, and involuntary writhing movements of the limbs (athetosis). This condition may also cause infants to lack energy, feed poorly, startle easily, and have sleep disturbances.^[1]

Many people with AADC deficiency experience episodes called oculogyric crises (also called "spells" or "attacks"), which are characterized by abnormal rotation of the eyeballs, extreme irritability and agitation, pain, muscle spasms, and uncontrolled movements of the head and neck.^[1]^[2]. These episodes can last for many hours and can be times of extreme concern for caregivers and family members.^[2]

AADC deficiency may also affect the autonomic nervous system, which controls involuntary body processes like regulation of blood pressure and body temperature. Autonomic symptoms may include droopy eye lids (ptosis), constriction of the pupils of the eyes (miosis), inappropriate or impaired sweating, nasal congestion, drooling, reduced ability to control body temperature, low blood pressure (hypotension), gastroesophageal reflux, low blood sugar (hypoglycemia), fainting (syncope), and cardiac arrest.^[1]

The signs and symptoms of AADC deficiency tend to worsen late in the day or when the individual is tired, and symptoms tend to improve after sleep.^[1]

Last updated: 7/14/2017

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormality of the face	-
Autosomal recessive inheritance	-
Babinski sign	-
Choreoathetosis	-
Constipation	-
Decreased CSF homovanillic acid	-
Diarrhea	-
Emotional lability	-
Feeding difficulties in infancy	-
Gastroesophageal reflux	-
Hyperhidrosis	-
Hyperreflexia	-
Hypotension	-
Infantile onset	-
Intermittent hypothermia	-
Irritability	-
Limb dystonia	-
Limb hypertonia	-
Miosis	-
Muscular hypotonia of the trunk	-
Myoclonus	-
Ptosis	-
Sleep disturbance	-
Temperature instability	-

Last updated: 9/1/2017

Cause Cause

Aromatic l-amino acid decarboxylase (AADC) deficiency is caused by changes (mutations) in the DDC gene. This gene provides instructions to the body to create an enzyme called the AADC enzyme. When this enzyme is working properly, it creates neurotransmitters called dopamine and serotonin. These neurotransmitters allow the cells of the nervous system to communicate with each other properly.^[1]

When there is a mutation in DDC, the body does not create AADC enzyme correctly, and there are not enough properly working neurotransmitters in the body. These changes therefore cause the symptoms associated with AADC deficiency.^[1]

Last updated: 7/14/2017

Inheritance Inheritance

Aromatic l-amino acid decarboxylase (AADC) deficiency is inherited in an autosomal recessive manner.^[1] This means that both copies of the DDC gene must be changed in order to have symptoms of the disease. We inherit one copy of each gene from our mother and the other from out father.

People with a mutation in only one copy of the DDC gene are known as carriers. When two carriers of AADC deficiency have children together, for each child there is a:

25% chance that the child will have AADC deficiency
50% chance that the child will be a carrier of AADC deficiency like the parents
25% chance that the child will have two working copies of DDC, so the child will not have AADC deficiency and will not be a carrier.

Last updated: 7/14/2017

Diagnosis Diagnosis

Aromatic l-amino acid decarboxylase (AADC) deficiency is typically diagnosed based on a number of laboratory tests. A spinal tap may be completed to measure levels of substances related to having low levels of dopamine and serotonin. A blood sample can also be taken to measure the activity of the AADC enzyme.^[3]

If these tests are consistent with an individual having AADC deficiency, genetic testing can be completed to confirm the diagnosis. It is recommended that doctors use at least two of these methods to diagnose a person with AADC deficiency.^[4]

Last updated: 7/14/2017

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

There is currently no cure for aromatic L-amino acid decarboxylase (AADC) deficiency. Different medications can be used to help treat the signs and symptoms of the disease. However, although certain combinations of medications may help some people, there is no proven strategy that relieves the symptoms of all people with this disease.^[3] Whether or a not a treatment works may depend on the exact change in the DDC gene and how much the AADC enzyme is functioning in the body.^[5]

Since the nervous system in a child with AADC deficiency does not have enough of certain neurotransmitters, the goal of many of the treatments is to make certain as much of these neurotransmitters are available as possible.^[4]

Medication could include any one or combination of the following:^[4]

Other treatments may depend on the symptoms of each individual. These treatment options include:^[4]

Anticholinergic agents to treat movement disorders
Seizure medication
Gastrointestinal medications
Melatonin to treat sleep disturbances

Physical, occupational, and speech therapy may also be helpful in improving symptoms of the disease.^[2]^[4]

G ene therapy treatment for AADC deficiency seems promising in mice with the disease (animal models),^[6] and clinical studies in humans are currently taking place to learn more about if the treatment is effective and safe.

Last updated: 7/14/2017

Prognosis Prognosis

There is limited information available about the long-term outlook for people diagnosed with aromatic l-amino acid decarboxylase (AADC) deficiency. There can be a wide variation in the severity of symptoms in people with the disease.^[7] It is not expected that the severity of symptoms should increase as an affected individual gets older. However, in some cases new symptoms may develop as side effects to other symptoms. For example, some people with AADC deficiency may develop joint contractures (inability to move joints) due to the movement disorders associated with the disease.^[4]

Some of the symptoms associated with AADC deficiency, such as problems controlling the autonomic nervous system, may be life-threatening in moments of stress. It is important to follow the doctor’s recommendations for monitoring the symptoms of people with AADC deficiency and to know what to do in case of an emergency.^[4]

Last updated: 7/14/2017

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Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Aromatic L-amino acid decarboxylase deficiency. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Pediatric Neurotransmitter Disease Association
28 Prescott Place
Old Bethpage, NY 11804
Telephone: 603-733-8409
E-mail: pnd@pndassociation.org
Website: http://www.pndassoc.org/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Aromatic L-amino acid decarboxylase deficiency. This website is maintained by the National Library of Medicine.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Aromatic L-amino acid decarboxylase deficiency. Click on the link to view a sample search on this topic.

News & Events News & Events

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References References

Aromatic l-amino acid decarboxylase deficiency. Genetics Home Reference (GHR). May 2008; https://ghr.nlm.nih.gov/condition/aromatic-l-amino-acid-decarboxylase-deficiency.
What is Aromatic L-Amino Acid Decarboxylase Deficiency?. Pediatric Neurotransmitter Disease Association. http://www.pndassoc.org/diseases/aadc.html. Accessed 7/7/2017.
Chien YH, Chen PW, Lee NC, Hsieh WS, Chiu PC, Hwu WL, Tsai FJ, Lin SP, Chu SY, Jong YJ, and Chao MC. 3-O-methyldopa levels in newborns: Result of newborn screening for aromatic l-aminio acid decarboxylase deficiency. Molecular Genetics and Metabolism. August 2016; 118(4):259-263. https://www.ncbi.nlm.nih.gov/pubmed/27216367.
Wassenberg T, Molero-Luis M, Jeltsch K, Hoffmann G, Assmann B, Blau N, Garcia-Carzola A, Artuch R, Pons R, Pearson TS, Leuzzi V, Mastrangelo M, Pearl PL, Lee WT, Kurian MA, Heales S, Flint L, Verbeek M, Willemsen M, and Opladen T. Consensus guideline for the diagnosis and treatment of aromatic l-amino acid decarboxylase (AADC) deficiency. Orphanet Journal of Rare Diseases. 2017; 12:12:https://ojrd.biomedcentral.com/track/pdf/10.1186/s13023-016-0522-z?site=ojrd.biomedcentral.com.
Kojima K, Anzai R, Ohba C, Goto T, Miyauchi A, Thöny B, Saitsu H, Matsumoto N, Osaka H, and Yamagata T. A female case of aromatic l-amino acid decarboxylase deficiency responsive to MAO-B inhibition. Brain Dev. November 2016; 38(10):959-963. https://www.ncbi.nlm.nih.gov/pubmed/27371992.
Lee NC, Muramatsu SI,Chien YH, Liu WS, Wang WH, Cheng CH, Hu MK, Chen PW, Tzen KY, Byrne BJ, and Hwu WL. Benefits of Neuronal Preferential Systemic Gene Therapy for Neurotransmitter Deficiency. Molecular Therapy. October 2015; 23(10):1572-1581. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817920.
Helman G, Pappa MB, and Pearl PL. Widening Phenotypic Spectrum of AADC Deficiency, a Disorder of Dopamine and Serotonin Synthesis. JIMD Reports. 2014; 17:23-27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4241195/.
Alfadhel M and Kattan R. Aromatic Amino Acid Decarboxylase Deficiency Not Responding to Pyridoxine and Bromocriptine Therapy: Case Report and Review of Response to Treatment. Journal of Central Nervous System Disease. January 7 2014; 6:1-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891626.