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Deficiency of aromatic-L-amino-acid decarboxylase(AADCD)

MedGen UID:
220945
Concept ID:
C1291564
Disease or Syndrome
Synonyms: Aromatic amino acid decarboxylase deficiency; Aromatic L-Amino Acid Decarboxylase Deficiency; DDC deficiency; Dopa decarboxylase deficiency
SNOMED CT: Deficiency of tryptophan decarboxylase (124600004); Deficiency of hydroxytryptophan decarboxylase (124600004); Deficiency of dopa decarboxylase (124600004); Deficiency of aromatic-L-amino-acid decarboxylase (124600004)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): DDC (7p12.2-12.1)
 
Monarch Initiative: MONDO:0012084
OMIM®: 608643
Orphanet: ORPHA35708

Definition

Aromatic L-amino acid decarboxylase deficiency (AADCD) is an autosomal recessive inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency (Abeling et al., 2000). The disorder is clinically characterized by vegetative symptoms, oculogyric crises, dystonia, and severe neurologic dysfunction, usually beginning in infancy or childhood (summary by Brun et al., 2010). [from OMIM]

Additional description

From MedlinePlus Genetics
Aromatic l-amino acid decarboxylase (AADC) deficiency is an inherited disorder that affects the way nerve cells (neurons) transmit information to other cells.

Signs and symptoms of AADC deficiency typically appear in the first six months of life. Affected infants may have feeding problems, weak muscle tone (hypotonia), and sleep disturbances. Most children with AADC deficiency experience episodes called oculogyric crises that involve involuntary upward-rolling movements of the eyes. Additional signs and symptoms typically include developmental delays and intellectual disabilities. 

Movement disorders are common in people with AADC deficiency. Involuntary movements that can occur in people with AADC deficiency include muscle contractions that may cause unusual body positions (dystonia) and writhing movements of the limbs (athetosis). Dystonia tends to become worse when the individual is tired, but it usually improves after sleep. Affected individuals may also experience slow or diminished movements (hypokinesia). 

AADC deficiency may also affect the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. This can lead to signs and symptoms such as droopy eyelids (ptosis), constriction of the pupils of the eyes (miosis), inappropriate or impaired sweating, nasal congestion, drooling, poor control of body temperature, low blood pressure (hypotension), low blood glucose (hypoglycemia), and abnormal heart rhythms.

People with AADC deficiency have an increased risk of infection, which can lead to life-threatening complications.    https://medlineplus.gov/genetics/condition/aromatic-l-amino-acid-decarboxylase-deficiency

Clinical features

From HPO
Limb hypertonia
MedGen UID:
333083
Concept ID:
C1838391
Finding
Hypotension
MedGen UID:
5715
Concept ID:
C0020649
Finding
Low Blood Pressure, vascular hypotension.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Athetosis
MedGen UID:
2115
Concept ID:
C0004158
Disease or Syndrome
A slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Athetosis involves continuous smooth movements that appear random and are not composed of recognizable sub-movements or movement fragments. In contrast to chorea, in athetosis, the same regions of the body are repeatedly involved. Athetosis may worsen with attempts at movement of posture, but athetosis can also occur at rest.
Lethargy
MedGen UID:
7310
Concept ID:
C0023380
Sign or Symptom
A state of disinterest, listlessness, and indifference, resulting in difficulty performing simple tasks or concentrating.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Sleep abnormality
MedGen UID:
52372
Concept ID:
C0037317
Finding
An abnormal pattern in the quality, quantity, or characteristics of sleep.
Torticollis
MedGen UID:
11859
Concept ID:
C0040485
Sign or Symptom
Torticollis is a twisted neck as a result of shortening of sternocleidomastoid muscle. This short and fibrotic muscle pulls the head laterally and rotates the chin and face to the opposite end. Facial asymmetry may be a manifestation (summary by Engin et al., 1997).
Choreoathetosis
MedGen UID:
39313
Concept ID:
C0085583
Disease or Syndrome
Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).
Emotional lability
MedGen UID:
39319
Concept ID:
C0085633
Mental or Behavioral Dysfunction
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.
Oculogyric crisis
MedGen UID:
43221
Concept ID:
C0085637
Pathologic Function
An acute dystonic reaction with blepharospasm, periorbital twitches, and protracted fixed staring episodes. There may be a maximal upward deviation of the eyes in the sustained fashion. Oculogyric crisis can be triggered by a number of factors including neuroleptic medications.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Limb tremor
MedGen UID:
115980
Concept ID:
C0235081
Sign or Symptom
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Limb dystonia
MedGen UID:
152944
Concept ID:
C0751093
Sign or Symptom
A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the limbs.
Exaggerated startle response
MedGen UID:
329357
Concept ID:
C1740801
Finding
An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face.
Tongue thrusting
MedGen UID:
473491
Concept ID:
C1829460
Finding
Pressing forward of the tongue in the mouth, a retained motoric habit from infantile swallowing patterns
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
Diminished movement
MedGen UID:
871229
Concept ID:
C4025710
Finding
Decreased CSF homovanillic acid concentration
MedGen UID:
1813045
Concept ID:
C5676596
Finding
Decreased concentration of homovanillic acid (HVA) in the cerebrospinal fluid. HVA is a metabolite of dopamine.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Sign or Symptom
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Cardiorespiratory arrest
MedGen UID:
154664
Concept ID:
C0600228
Pathologic Function
Cessation of breathing and/or cardiac function.
Temperature instability
MedGen UID:
329973
Concept ID:
C1820737
Finding
Disordered thermoregulation characterized by an impaired ability to maintain a balance between heat production and heat loss, with resulting instability of body temperature.
Intermittent hypothermia
MedGen UID:
332504
Concept ID:
C1837639
Finding
Episodes of reduced body temperature.
Reduced circulating aromatic L-amino acid decarboxylase activity
MedGen UID:
1053308
Concept ID:
CN376549
Finding
The activity of aromatic L-amino acid decarboxylase (also known as DOPA decarboxylase, tryptophan decarboxylase, and 5-hydroxytryptophan decarboxylase) in the blood circulation is below the lower limit of normal.
Blepharospasm
MedGen UID:
599
Concept ID:
C0005747
Disease or Syndrome
A focal dystonia that affects the muscles of the eyelids and brow, associated with involuntary recurrent spasm of both eyelids.
Nasal congestion
MedGen UID:
6523
Concept ID:
C0027424
Sign or Symptom
Reduced ability to pass air through the nasal cavity often leading to mouth breathing.
Abnormality of the face
MedGen UID:
871375
Concept ID:
C4025871
Anatomical Abnormality
An abnormality of the face.
Hyperhidrosis
MedGen UID:
5690
Concept ID:
C0020458
Finding
Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Miosis
MedGen UID:
6409
Concept ID:
C0026205
Disease or Syndrome
Abnormal (non-physiological) constriction of the pupil.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDeficiency of aromatic-L-amino-acid decarboxylase
Follow this link to review classifications for Deficiency of aromatic-L-amino-acid decarboxylase in Orphanet.

Professional guidelines

PubMed

Sternberg Z
Mol Neurobiol 2024 May;61(5):2996-3018. Epub 2023 Nov 13 doi: 10.1007/s12035-023-03684-2. PMID: 37953352
Burlina A, Giuliani A, Polo G, Gueraldi D, Gragnaniello V, Cazzorla C, Opladen T, Hoffmann G, Blau N, Burlina AP
Mol Genet Metab 2021 May;133(1):56-62. Epub 2021 Mar 13 doi: 10.1016/j.ymgme.2021.03.009. PMID: 33744095
Allen GF, Land JM, Heales SJ
Mol Genet Metab 2009 May;97(1):6-14. Epub 2009 Jan 27 doi: 10.1016/j.ymgme.2009.01.010. PMID: 19231266

Recent clinical studies

Etiology

Pons R, Ford B, Chiriboga CA, Clayton PT, Hinton V, Hyland K, Sharma R, De Vivo DC
Neurology 2004 Apr 13;62(7):1058-65. doi: 10.1212/wnl.62.7.1058. PMID: 15079002

Diagnosis

Pons R, Ford B, Chiriboga CA, Clayton PT, Hinton V, Hyland K, Sharma R, De Vivo DC
Neurology 2004 Apr 13;62(7):1058-65. doi: 10.1212/wnl.62.7.1058. PMID: 15079002
Lamers KJ, Wevers RA
Mult Scler 1998 Feb;4(1):37-8. doi: 10.1177/135245859800400109. PMID: 9532591

Therapy

Pons R, Ford B, Chiriboga CA, Clayton PT, Hinton V, Hyland K, Sharma R, De Vivo DC
Neurology 2004 Apr 13;62(7):1058-65. doi: 10.1212/wnl.62.7.1058. PMID: 15079002
Surtees R, Hyland K
J Neurol Neurosurg Psychiatry 1990 Jul;53(7):569-72. doi: 10.1136/jnnp.53.7.569. PMID: 2391519Free PMC Article

Prognosis

Pons R, Ford B, Chiriboga CA, Clayton PT, Hinton V, Hyland K, Sharma R, De Vivo DC
Neurology 2004 Apr 13;62(7):1058-65. doi: 10.1212/wnl.62.7.1058. PMID: 15079002

Clinical prediction guides

Surtees R, Hyland K
J Neurol Neurosurg Psychiatry 1990 Jul;53(7):569-72. doi: 10.1136/jnnp.53.7.569. PMID: 2391519Free PMC Article

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