MCID: ARM002
MIFTS: 39

Aromatic L-Amino Acid Decarboxylase Deficiency

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Aromatic L-Amino Acid Decarboxylase Deficiency

MalaCards integrated aliases for Aromatic L-Amino Acid Decarboxylase Deficiency:

Name: Aromatic L-Amino Acid Decarboxylase Deficiency 54 12 50 24 25 56 13
Dopa Decarboxylase Deficiency 50 24 25 71
Aadc Deficiency 12 50 25 56
Deficiency of Aromatic-L-Amino-Acid Decarboxylase 25 29 69
Ddc Deficiency 50 25 71
Aromatic Amino Acid Decarboxylase Deficiency 50 69
Aromatic L-Amino-Acid Decarboxylase Deficiency 71
Aromatic-L-Amino-Acid Decarboxylase Deficiency 71
Dopa Decarboxylase 13
Aadcd 71

Characteristics:

Orphanet epidemiological data:

56
aromatic l-amino acid decarboxylase deficiency
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in early infancy
drug-induced dyskinesias occur in a subset of patients
diurnal fluctuation of symptoms


HPO:

32
aromatic l-amino acid decarboxylase deficiency:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Aromatic L-Amino Acid Decarboxylase Deficiency

NIH Rare Diseases : 50 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. 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. aadc deficiency is caused by mutations in the ddc gene. the disease is inherited in an autosomal recessive manner. 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. 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.  last updated: 7/14/2017

MalaCards based summary : Aromatic L-Amino Acid Decarboxylase Deficiency, also known as dopa decarboxylase deficiency, is related to epilepsy and hypoglycemia, and has symptoms including myoclonus, diarrhea and hyperreflexia. An important gene associated with Aromatic L-Amino Acid Decarboxylase Deficiency is DDC (Dopa Decarboxylase). The drugs Antiparkinson Agents and Dihydroxyphenylalanine have been mentioned in the context of this disorder. Affiliated tissues include testes, heart and whole blood.

Disease Ontology : 12 An inherited metabolic disorder characterized by reduced production of serotonin and dopamine resulting in hypotonia, hypokinesia, ptosis oculogyric crises, and signs of autonomic dysfunction with onset in infancy or childhood that has material basis in homozygous or compound heterozygous mutation in the DDC gene on chromosome 7p12.

Genetics Home Reference : 25 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.

OMIM : 54
AADC deficiency 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). (608643)

UniProtKB/Swiss-Prot : 71 Aromatic L-amino-acid decarboxylase deficiency: An inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency. It causes developmental and psychomotor delay, poor feeding, lethargy, ptosis, intermittent hypothermia, gastrointestinal disturbances. The onset is early in infancy and inheritance is autosomal recessive.

Related Diseases for Aromatic L-Amino Acid Decarboxylase Deficiency

Diseases related to Aromatic L-Amino Acid Decarboxylase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 epilepsy 10.0
2 hypoglycemia 10.0
3 fasting hypoglycemia 10.0
4 encephalopathy 10.0
5 neuroblastoma 9.8

Graphical network of the top 20 diseases related to Aromatic L-Amino Acid Decarboxylase Deficiency:



Diseases related to Aromatic L-Amino Acid Decarboxylase Deficiency

Symptoms & Phenotypes for Aromatic L-Amino Acid Decarboxylase Deficiency

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
myoclonus
hyperreflexia
extensor plantar responses
sleep disturbances
developmental delay
more
Head And Neck- Eyes:
ptosis
oculogyric crises
miosis

Cardiovascular- Vascular:
hypotension

Metabolic Features:
paroxysmal sweating
intermittent hypothermia
temperature instability

Abdomen- Gastroin testinal:
diarrhea
poor feeding
constipation
gastroesophageal reflux disease

Neurologic- Behavioral Psychiatric Manifestations:
emotional lability
irritability

Head And Neck- Nose:
nasal congestion

Laboratory- Abnormalities:
decreased activity of aromatic l-amino acid decarboxylase (aadc)
decreased csf homovanillic acid (hva)
decreased csf 5-hydroxyindoleacetic acid (5-hiaa)
decreased plasma catecholamines
decreased whole blood serotonin
more

Clinical features from OMIM:

608643

Human phenotypes related to Aromatic L-Amino Acid Decarboxylase Deficiency:

32 (show all 23)
id Description HPO Frequency HPO Source Accession
1 myoclonus 32 HP:0001336
2 diarrhea 32 HP:0002014
3 hyperreflexia 32 HP:0001347
4 choreoathetosis 32 HP:0001266
5 ptosis 32 HP:0000508
6 emotional lability 32 HP:0000712
7 irritability 32 HP:0000737
8 global developmental delay 32 HP:0001263
9 gastroesophageal reflux 32 HP:0002020
10 constipation 32 HP:0002019
11 limb hypertonia 32 HP:0002509
12 feeding difficulties in infancy 32 HP:0008872
13 hyperhidrosis 32 HP:0000975
14 hypotension 32 HP:0002615
15 limb dystonia 32 HP:0002451
16 babinski sign 32 HP:0003487
17 miosis 32 HP:0000616
18 intermittent hypothermia 32 HP:0005964
19 temperature instability 32 HP:0005968
20 sleep disturbance 32 HP:0002360
21 abnormality of the face 32 HP:0000271
22 muscular hypotonia of the trunk 32 HP:0008936
23 decreased csf homovanillic acid 32 HP:0003785

UMLS symptoms related to Aromatic L-Amino Acid Decarboxylase Deficiency:


constipation, diarrhea, myoclonus, nasal congestion (finding), sleep disturbances, dystonia, limb

Drugs & Therapeutics for Aromatic L-Amino Acid Decarboxylase Deficiency

Drugs for Aromatic L-Amino Acid Decarboxylase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Antiparkinson Agents Phase 1, Phase 2
2 Dihydroxyphenylalanine Phase 1, Phase 2
3 Dopa Decarboxylase Phase 1, Phase 2

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 A Phase I/II Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC Completed NCT01395641 Phase 1, Phase 2 gene therapy
2 A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC - An Expansion Recruiting NCT02926066 Phase 2 AAV2-hAADC
3 A Single-Stage, Adaptive, Open-label, Dose Escalation Safety and Efficacy Study of AADC Deficiency in Pediatric Patients Recruiting NCT02852213 Phase 1 AAV2-hAADC
4 Newborn Screening for Aromatic L-amino Acid Decarboxylase Deficiency Completed NCT02399761

Search NIH Clinical Center for Aromatic L-Amino Acid Decarboxylase Deficiency

Genetic Tests for Aromatic L-Amino Acid Decarboxylase Deficiency

Genetic tests related to Aromatic L-Amino Acid Decarboxylase Deficiency:

id Genetic test Affiliating Genes
1 Deficiency of Aromatic-L-Amino-Acid Decarboxylase 29
2 Aromatic L-Amino Acid Decarboxylase Deficiency 24 DDC

Anatomical Context for Aromatic L-Amino Acid Decarboxylase Deficiency

MalaCards organs/tissues related to Aromatic L-Amino Acid Decarboxylase Deficiency:

39
Testes, Heart, Whole Blood, Brain

Publications for Aromatic L-Amino Acid Decarboxylase Deficiency

Articles related to Aromatic L-Amino Acid Decarboxylase Deficiency:

(show all 36)
id Title Authors Year
1
Natural History of Aromatic L-Amino Acid Decarboxylase Deficiency in Taiwan. ( 28856607 )
2017
2
Microstructural changes of brain in patients with aromatic L-amino acid decarboxylase deficiency. ( 27859928 )
2016
3
3-O-methyldopa levels in newborns: Result of newborn screening for aromatic l-amino-acid decarboxylase deficiency. ( 27216367 )
2016
4
A female case of aromatic l-amino acid decarboxylase deficiency responsive to MAO-B inhibition. ( 27371992 )
2016
5
Aromatic L-amino acid decarboxylase deficiency diagnosed by clinical metabolomic profiling of plasma. ( 25956449 )
2015
6
Report of two never treated adult sisters with aromatic L-amino Acid decarboxylase deficiency: a portrait of the natural history of the disease or an expanding phenotype? ( 24788355 )
2015
7
Diagnosis of aromatic L-amino acid decarboxylase deficiency by measuring 3-O-methyldopa concentrations in dried blood spots. ( 24513538 )
2014
8
A rare cause of severe diarrhoea diagnosed by urine metabolic screening: aromatic L-amino acid decarboxylase deficiency. ( 24714172 )
2014
9
Aromatic L-Amino acid decarboxylase deficiency: A new case from Turkey with a novel mutation. ( 25024584 )
2014
10
Regulation of the dopaminergic system in a murine model of aromatic L-amino acid decarboxylase deficiency. ( 23275025 )
2013
11
Transdermal rotigotine in the treatment of aromatic L-amino acid decarboxylase deficiency. ( 23390030 )
2013
12
Aromatic L-amino acid decarboxylase deficiency is a cause of long-fasting hypoglycemia. ( 24037885 )
2013
13
Non-invasive urinary screening for aromatic L-amino acid decarboxylase deficiency in high-prevalence areas: a pilot study. ( 21963339 )
2012
14
Gene therapy for aromatic L-amino acid decarboxylase deficiency. ( 22593174 )
2012
15
Gene therapy for aromatic L-amino acid decarboxylase deficiency. ( 22989964 )
2012
16
Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency. ( 20505134 )
2010
17
Urinary dopamine in aromatic L-amino acid decarboxylase deficiency: the unsolved paradox. ( 20832343 )
2010
18
Abnormal glucose metabolism in aromatic L-amino acid decarboxylase deficiency. ( 19520530 )
2010
19
A new perspective on the treatment of aromatic L-amino acid decarboxylase deficiency. ( 19231266 )
2009
20
Aromatic L-amino acid decarboxylase deficiency: clinical features, drug therapy and follow-up. ( 19172410 )
2009
21
Aromatic L-amino acid decarboxylase deficiency in Taiwan. ( 18567514 )
2009
22
Aromatic L-amino acid decarboxylase deficiency associated with epilepsy mimicking non-epileptic involuntary movements. ( 18754761 )
2008
23
Anesthesia management in a young child with aromatic l-amino acid decarboxylase deficiency. ( 16409536 )
2006
24
Combined general and regional anesthetic in a child with aromatic L-amino acid decarboxylase deficiency. ( 17122302 )
2006
25
Catecholamine toxicity in aromatic L-amino acid decarboxylase deficiency. ( 16876014 )
2006
26
Levodopa-responsive aromatic L-amino acid decarboxylase deficiency. ( 14991824 )
2004
27
Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis. ( 15079002 )
2004
28
Aromatic L-amino acid decarboxylase deficiency: overview of clinical features and outcomes. ( 12891654 )
2003
29
Clinical and laboratory findings in twins with neonatal epileptic encephalopathy mimicking aromatic L-amino acid decarboxylase deficiency. ( 12200739 )
2002
30
Aromatic L-amino acid decarboxylase deficiency with hyperdopaminuria. Clinical and laboratory findings in response to different therapies. ( 12368991 )
2002
31
The influence of L-dopa on methylation capacity in aromatic L-amino acid decarboxylase deficiency: biochemical findings in two patients. ( 10896284 )
2000
32
Clinical and therapeutic observations in aromatic L-amino acid decarboxylase deficiency. ( 10522874 )
1999
33
Aromatic L-amino acid decarboxylase deficiency: an extrapyramidal movement disorder with oculogyric crises. ( 10728198 )
1997
34
Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and treatment of a second family. ( 9309516 )
1997
35
Aromatic L-amino acid decarboxylase deficiency: diagnostic methodology. ( 1281049 )
1992
36
Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and treatment of a new inborn error of neurotransmitter amine synthesis. ( 1357595 )
1992

Variations for Aromatic L-Amino Acid Decarboxylase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Aromatic L-Amino Acid Decarboxylase Deficiency:

71
id Symbol AA change Variation ID SNP ID
1 DDC p.Gly102Ser VAR_019309 rs137853207
2 DDC p.Pro47His VAR_046137 rs780542462
3 DDC p.Ala91Val VAR_046138 rs137853211
4 DDC p.Ser147Arg VAR_046139 rs137853210
5 DDC p.Ser250Phe VAR_046140 rs137853208
6 DDC p.Ala275Thr VAR_046141 rs137853212
7 DDC p.Phe309Leu VAR_046142 rs137853209
8 DDC p.Arg347Gln VAR_046143 rs201951824
9 DDC p.Leu408Ile VAR_046144

ClinVar genetic disease variations for Aromatic L-Amino Acid Decarboxylase Deficiency:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 DDC NM_001082971.1(DDC): c.304G> A (p.Gly102Ser) single nucleotide variant Pathogenic rs137853207 GRCh37 Chromosome 7, 50607624: 50607624
2 DDC NM_001082971.1(DDC): c.749C> T (p.Ser250Phe) single nucleotide variant Pathogenic rs137853208 GRCh37 Chromosome 7, 50571723: 50571723
3 DDC NM_001082971.1(DDC): c.925T> C (p.Phe309Leu) single nucleotide variant Pathogenic rs137853209 GRCh37 Chromosome 7, 50563067: 50563067
4 DDC NM_001082971.1(DDC): c.439A> C (p.Ser147Arg) single nucleotide variant Pathogenic rs137853210 GRCh37 Chromosome 7, 50597037: 50597037
5 DDC NM_001082971.1(DDC): c.272C> T (p.Ala91Val) single nucleotide variant Pathogenic rs137853211 GRCh37 Chromosome 7, 50607656: 50607656
6 DDC NM_001082971.1(DDC): c.823G> A (p.Ala275Thr) single nucleotide variant Pathogenic rs137853212 GRCh37 Chromosome 7, 50566899: 50566899
7 DDC DDC, IVS6DS, A-T, +4 single nucleotide variant Pathogenic
8 DDC NM_001082971.1(DDC): c.1040G> A (p.Arg347Gln) single nucleotide variant Pathogenic rs201951824 GRCh37 Chromosome 7, 50544323: 50544323

Expression for Aromatic L-Amino Acid Decarboxylase Deficiency

Search GEO for disease gene expression data for Aromatic L-Amino Acid Decarboxylase Deficiency.

Pathways for Aromatic L-Amino Acid Decarboxylase Deficiency

GO Terms for Aromatic L-Amino Acid Decarboxylase Deficiency

Sources for Aromatic L-Amino Acid Decarboxylase Deficiency

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