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 53 12 49 24 55 13
Aadc Deficiency 53 12 49 24 55
Dopa Decarboxylase Deficiency 53 49 24 71
Ddc Deficiency 53 49 24 71
Deficiency of Aromatic-L-Amino-Acid Decarboxylase 24 28 69
Aromatic Amino Acid Decarboxylase Deficiency 49 69
Aromatic L-Amino Acid Decarboxylase Deficiency 36
Aromatic L-Amino-Acid Decarboxylase Deficiency 71
Aromatic-L-Amino-Acid Decarboxylase Deficiency 71
Dopa Decarboxylase 13
Aadcd 71

Characteristics:

Orphanet epidemiological data:

55
aromatic l-amino acid decarboxylase deficiency
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal recessive

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


HPO:

31
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 : 49 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 aadc deficiency, is related to epilepsy and hypoglycemia, and has symptoms including constipation, myoclonus and diarrhea. An important gene associated with Aromatic L-Amino Acid Decarboxylase Deficiency is DDC (Dopa Decarboxylase), and among its related pathways/superpathways are Tyrosine metabolism and Tryptophan metabolism. The drugs Antiparkinson Agents and Dihydroxyphenylalanine have been mentioned in the context of this disorder. Affiliated tissues include heart, testes 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 : 24 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 : 53 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:

(showing 5, show less)
# Related Disease Score Top Affiliating Genes
1 epilepsy 10.1
2 hypoglycemia 10.1
3 fasting hypoglycemia 10.1
4 encephalopathy 10.1
5 neuroblastoma 9.9

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:

53
Abdomen Gastroin testinal:
constipation
diarrhea
poor feeding
gastroesophageal reflux disease

Head And Neck Eyes:
ptosis
miosis
oculogyric crises

Cardiovascular Vascular:
hypotension

Laboratory Abnormalities:
decreased csf homovanillic acid (hva)
decreased activity of aromatic l-amino acid decarboxylase (aadc)
decreased csf 5-hydroxyindoleacetic acid (5-hiaa)
decreased plasma catecholamines
decreased whole blood serotonin
more
Neurologic Central Nervous System:
sleep disturbances
myoclonus
hyperreflexia
choreoathetosis
limb dystonia
more
Neurologic Behavioral Psychiatric Manifestations:
emotional lability
irritability

Metabolic Features:
temperature instability
paroxysmal sweating
intermittent hypothermia

Head And Neck Nose:
nasal congestion


Clinical features from OMIM:

608643

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

31 (showing 23, show less)
# Description HPO Frequency HPO Source Accession
1 constipation 31 HP:0002019
2 myoclonus 31 HP:0001336
3 diarrhea 31 HP:0002014
4 ptosis 31 HP:0000508
5 emotional lability 31 HP:0000712
6 hyperhidrosis 31 HP:0000975
7 hyperreflexia 31 HP:0001347
8 sleep disturbance 31 HP:0002360
9 hypotension 31 HP:0002615
10 global developmental delay 31 HP:0001263
11 gastroesophageal reflux 31 HP:0002020
12 feeding difficulties in infancy 31 HP:0008872
13 irritability 31 HP:0000737
14 babinski sign 31 HP:0003487
15 choreoathetosis 31 HP:0001266
16 miosis 31 HP:0000616
17 limb dystonia 31 HP:0002451
18 limb hypertonia 31 HP:0002509
19 muscular hypotonia of the trunk 31 HP:0008936
20 temperature instability 31 HP:0005968
21 nasal obstruction 31 HP:0001742
22 intermittent hypothermia 31 HP:0005964
23 decreased csf homovanillic acid 31 HP:0003785

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


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

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):

(showing 3, show less)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Antiparkinson Agents Phase 2,Phase 1
2 Dihydroxyphenylalanine Phase 2,Phase 1
3 Dopa Decarboxylase Phase 2,Phase 1

Interventional clinical trials:

(showing 4, show less)

# Name Status NCT ID Phase Drugs
1 A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC - An Expansion Recruiting NCT02926066 Phase 2 AAV2-hAADC
2 A Phase I/II Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC Active, not recruiting NCT01395641 Phase 1, Phase 2 gene therapy
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:

# Genetic test Affiliating Genes
1 Deficiency of Aromatic-L-Amino-Acid Decarboxylase 28 DDC

Anatomical Context for Aromatic L-Amino Acid Decarboxylase Deficiency

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

38
Heart, Testes, Whole Blood, Brain

Publications for Aromatic L-Amino Acid Decarboxylase Deficiency

Articles related to Aromatic L-Amino Acid Decarboxylase Deficiency:

(showing 36, show less)
# Title Authors Year
1
Natural History of Aromatic L-Amino Acid Decarboxylase Deficiency in Taiwan. ( 28856607 )
2017
2
A female case of aromatic l-amino acid decarboxylase deficiency responsive to MAO-B inhibition. ( 27371992 )
2016
3
3-O-methyldopa levels in newborns: Result of newborn screening for aromatic l-amino-acid decarboxylase deficiency. ( 27216367 )
2016
4
Microstructural changes of brain in patients with aromatic L-amino acid decarboxylase deficiency. ( 27859928 )
2016
5
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
6
Aromatic L-amino acid decarboxylase deficiency diagnosed by clinical metabolomic profiling of plasma. ( 25956449 )
2015
7
A rare cause of severe diarrhoea diagnosed by urine metabolic screening: aromatic L-amino acid decarboxylase deficiency. ( 24714172 )
2014
8
Diagnosis of aromatic L-amino acid decarboxylase deficiency by measuring 3-O-methyldopa concentrations in dried blood spots. ( 24513538 )
2014
9
Aromatic L-Amino acid decarboxylase deficiency: A new case from Turkey with a novel mutation. ( 25024584 )
2014
10
Transdermal rotigotine in the treatment of aromatic L-amino acid decarboxylase deficiency. ( 23390030 )
2013
11
Aromatic L-amino acid decarboxylase deficiency is a cause of long-fasting hypoglycemia. ( 24037885 )
2013
12
Regulation of the dopaminergic system in a murine model of aromatic L-amino acid decarboxylase deficiency. ( 23275025 )
2013
13
Gene therapy for aromatic L-amino acid decarboxylase deficiency. ( 22593174 )
2012
14
Gene therapy for aromatic L-amino acid decarboxylase deficiency. ( 22989964 )
2012
15
Non-invasive urinary screening for aromatic L-amino acid decarboxylase deficiency in high-prevalence areas: a pilot study. ( 21963339 )
2012
16
Abnormal glucose metabolism in aromatic L-amino acid decarboxylase deficiency. ( 19520530 )
2010
17
Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency. ( 20505134 )
2010
18
Urinary dopamine in aromatic L-amino acid decarboxylase deficiency: the unsolved paradox. ( 20832343 )
2010
19
Aromatic L-amino acid decarboxylase deficiency: clinical features, drug therapy and follow-up. ( 19172410 )
2009
20
Aromatic L-amino acid decarboxylase deficiency in Taiwan. ( 18567514 )
2009
21
A new perspective on the treatment of aromatic L-amino acid decarboxylase deficiency. ( 19231266 )
2009
22
Aromatic L-amino acid decarboxylase deficiency associated with epilepsy mimicking non-epileptic involuntary movements. ( 18754761 )
2008
23
Catecholamine toxicity in aromatic L-amino acid decarboxylase deficiency. ( 16876014 )
2006
24
Anesthesia management in a young child with aromatic l-amino acid decarboxylase deficiency. ( 16409536 )
2006
25
Combined general and regional anesthetic in a child with aromatic L-amino acid decarboxylase deficiency. ( 17122302 )
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: clinical features, diagnosis, and treatment of a second family. ( 9309516 )
1997
34
Aromatic L-amino acid decarboxylase deficiency: an extrapyramidal movement disorder with oculogyric crises. ( 10728198 )
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 (showing 9, show less)
# 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 (showing 10, show less)
# 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
9 DDC NM_000790.3(DDC): c.1073G> A (p.Arg358His) single nucleotide variant Pathogenic/Likely pathogenic rs771317809 GRCh37 Chromosome 7, 50537838: 50537838
10 DDC NM_001082971.1(DDC): c.1352G> T (p.Cys451Phe) single nucleotide variant Likely pathogenic GRCh38 Chromosome 7, 50463322: 50463322

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

Pathways related to Aromatic L-Amino Acid Decarboxylase Deficiency according to KEGG:

36
(showing 4, show less)
# Name Kegg Source Accession
1 Tyrosine metabolism hsa00350
2 Tryptophan metabolism hsa00380
3 Serotonergic synapse hsa04726
4 Dopaminergic synapse hsa04728

GO Terms for Aromatic L-Amino Acid Decarboxylase Deficiency

Sources for Aromatic L-Amino Acid Decarboxylase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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