Rare Hematology News

Disease Profile

Aromatic L-amino acid decarboxylase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

G24.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Aromatic amino acid decarboxylase deficiency; AADC deficiency; DDC deficiency;

Categories

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders;

Summary

Aromatic lamino 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]

Symptoms

Symptoms of aromatic lamino 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]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Abnormality of the face
Abnormal face
Facial abnormality

[ more ]

0000271
Autosomal recessive inheritance
0000007
Babinski sign
0003487
Choreoathetosis
0001266
Constipation
0002019
Decreased CSF homovanillic acid
0003785
Diarrhea
Watery stool
0002014
Emotional lability
Emotional instability
0000712
Feeding difficulties in infancy
0008872
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Global developmental delay
0001263
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased

[ more ]

0000975
Hyperreflexia
Increased reflexes
0001347
Hypotension
Low blood pressure
0002615
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Intermittent hypothermia
Intermittent abnormally low body temperature
0005964
Irritability
Irritable
0000737
Limb dystonia
0002451
Limb hypertonia
Increased muscle tone of arm or leg
0002509
Miosis
Constricted pupils
Pupillary constriction

[ more ]

0000616
Muscular hypotonia of the trunk
Low muscle tone in trunk
0008936
Myoclonus
0001336
Nasal obstruction
Blockage of nose
Nasal blockage
Obstruction of nose
Stuffy nose

[ more ]

0001742
Ptosis
Drooping upper eyelid
0000508
Sleep disturbance
Difficulty sleeping
Trouble sleeping

[ more ]

0002360
Temperature instability
0005968

Cause

Aromatic lamino 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]

Diagnosis

Aromatic lamino 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]

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

    There is currently no cure for aromatic Lamino 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]

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

    Gene therapy treatment for AADC deficiency seems promising and clinical studies in humans are currently underway.

    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

      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.

          Selected Full-Text Journal Articles

            References

            1. Aromatic l-amino acid decarboxylase deficiency. Genetics Home Reference (GHR). May 2008; https://ghr.nlm.nih.gov/condition/aromatic-l-amino-acid-decarboxylase-deficiency.
            2. What is Aromatic L-Amino Acid Decarboxylase Deficiency?. Pediatric Neurotransmitter Disease Association. https://www.pndassoc.org/diseases/aadc.html. Accessed 7/7/2017.
            3. 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.
            4. 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.
            5. 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.
            6. 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/.
            7. 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.
            8. 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.

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