Aromatic l-amino acid decarboxylase (AADC) deficiency is an inherited disorder that affects the way signals are passed between certain cells in the nervous system.
Signs and symptoms of AADC deficiency generally appear in the first year of life. Affected infants may have severe developmental delay, weak muscle tone (hypotonia), muscle stiffness, difficulty moving, and involuntary writhing movements of the limbs (athetosis). They may be lacking in energy (lethargic), feed poorly, startle easily, and have sleep disturbances. People with AADC deficiency may also experience episodes called oculogyric crises that involve abnormal rotation of the eyeballs; extreme irritability and agitation; and pain, muscle spasms, and uncontrolled movements, especially of the head and neck.
AADC deficiency may affect the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. Resulting signs and symptoms can include droopy eyelids (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), backflow of acidic stomach contents into the esophagus (gastroesophageal reflux), low blood sugar (hypoglycemia), fainting (syncope), and cardiac arrest.
Signs and symptoms of AADC deficiency tend to worsen late in the day or when the individual is tired, and improve after sleep.
AADC deficiency is a rare disorder. Only about 100 people with this condition have been described in the medical literature worldwide; about 20 percent of these individuals are from Taiwan.
Mutations in the DDC gene cause AADC deficiency. The DDC gene provides instructions for making the AADC enzyme, which is important in the nervous system. This enzyme helps produce dopamine and serotonin from other molecules. Dopamine and serotonin are neurotransmitters, which are chemical messengers that transmit signals between nerve cells, both in the brain and spinal cord (central nervous system) and in other parts of the body (peripheral nervous system).
Mutations in the DDC gene result in reduced activity of the AADC enzyme. Without enough of this enzyme, nerve cells produce less dopamine and serotonin. Dopamine and serotonin are necessary for normal nervous system function, and changes in the levels of these neurotransmitters contribute to the developmental delay, intellectual disability, abnormal movements, and autonomic dysfunction seen in people with AADC deficiency.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- AADC deficiency
- DDC deficiency
- deficiency of aromatic-L-amino-acid decarboxylase
- dopa decarboxylase deficiency
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Research Studies from ClinicalTrials.gov
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
- Brun L, Ngu LH, Keng WT, Ch'ng GS, Choy YS, Hwu WL, Lee WT, Willemsen MA, Verbeek MM, Wassenberg T, Régal L, Orcesi S, Tonduti D, Accorsi P, Testard H, Abdenur JE, Tay S, Allen GF, Heales S, Kern I, Kato M, Burlina A, Manegold C, Hoffmann GF, Blau N. Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency. Neurology. 2010 Jul 6;75(1):64-71. doi: 10.1212/WNL.0b013e3181e620ae. Epub 2010 May 26. Erratum in: Neurology. 2010 Aug 10;75(6):576. Dosage error in article text. Citation on PubMed
- Hyland K, Surtees RA, Rodeck C, Clayton PT. Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and treatment of a new inborn error of neurotransmitter amine synthesis. Neurology. 1992 Oct;42(10):1980-8. Citation on PubMed
- Hyland K. Inherited disorders affecting dopamine and serotonin: critical neurotransmitters derived from aromatic amino acids. J Nutr. 2007 Jun;137(6 Suppl 1):1568S-1572S; discussion 1573S-1575S. doi: 10.1093/jn/137.6.1568S. Citation on PubMed
- Lee HC, Lai CK, Yau KC, Siu TS, Mak CM, Yuen YP, Chan KY, Tam S, Lam CW, Chan AY. Non-invasive urinary screening for aromatic L-amino acid decarboxylase deficiency in high-prevalence areas: a pilot study. Clin Chim Acta. 2012 Jan 18;413(1-2):126-30. doi: 10.1016/j.cca.2011.09.008. Epub 2011 Sep 21. Citation on PubMed
- Pearl PL, Capp PK, Novotny EJ, Gibson KM. Inherited disorders of neurotransmitters in children and adults. Clin Biochem. 2005 Dec;38(12):1051-8. Epub 2005 Nov 18. Review. Citation on PubMed
- Pearl PL, Taylor JL, Trzcinski S, Sokohl A. The pediatric neurotransmitter disorders. J Child Neurol. 2007 May;22(5):606-16. Review. Citation on PubMed
- Pons R, Ford B, Chiriboga CA, Clayton PT, Hinton V, Hyland K, Sharma R, De Vivo DC. Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis. Neurology. 2004 Apr 13;62(7):1058-65. Review. Citation on PubMed
- Swoboda KJ, Saul JP, McKenna CE, Speller NB, Hyland K. Aromatic L-amino acid decarboxylase deficiency: overview of clinical features and outcomes. Ann Neurol. 2003;54 Suppl 6:S49-55. Citation on PubMed
- Verbeek MM, Geurtz PB, Willemsen MA, Wevers RA. Aromatic L-amino acid decarboxylase enzyme activity in deficient patients and heterozygotes. Mol Genet Metab. 2007 Apr;90(4):363-9. Epub 2007 Jan 19. Citation on PubMed