MCID: DPM001
MIFTS: 49

Dopamine Beta-Hydroxylase Deficiency

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

Aliases & Classifications for Dopamine Beta-Hydroxylase Deficiency

MalaCards integrated aliases for Dopamine Beta-Hydroxylase Deficiency:

Name: Dopamine Beta-Hydroxylase Deficiency 54 12 23 24 25 56 71 13
Norepinephrine Deficiency 12 23 50 24 25 56 71
Noradrenaline Deficiency 12 50 25 56 71
Dopamine Beta Hydroxylase Deficiency 50 29 42 69
Dopamine Beta-Hydroxylase Deficiency, Congenital 50
Congenital Dopamine Beta-Hydroxylase Deficiency 12
Dopamine-Beta-Hydroxylase 13
Dopamine Β-Hydroxylase 25
Dbh Deficiency 71
Dbh 24

Characteristics:

Orphanet epidemiological data:

56
dopamine beta-hydroxylase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive


HPO:

32
dopamine beta-hydroxylase deficiency:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 54 223360
Disease Ontology 12 DOID:0090145
MeSH 42 C535600
Orphanet 56 ORPHA230
MESH via Orphanet 43 C535600
UMLS via Orphanet 70 C0342687
ICD10 via Orphanet 34 G90.8
UMLS 69 C0342687

Summaries for Dopamine Beta-Hydroxylase Deficiency

NIH Rare Diseases : 50 dopamine beta hydroxylase deficiency is a disease which affects the body’s ability to regulate blood pressure and body temperature. symptoms typically begin in late childhood and include vomiting, dehydration, low blood pressure, especially upon standing (orthostatic hypotension), and low blood sugar levels (hypoglycemia). low blood pressure can also cause dizziness, blurred vision, and difficulty exercising. some people have experienced drooping eyelids (ptosis), muscle pain, and weakness. dopamine beta hydroxylase deficiency is caused by mutation in the dbh gene and is inherited in an autosomal recessive manner. diagnosis is based on blood tests showing high dopamine levels and low norepinephrine levels. treatment with a synthetic form of norepinephrine can reduce hypotension.  last updated: 7/19/2016

MalaCards based summary : Dopamine Beta-Hydroxylase Deficiency, also known as norepinephrine deficiency, is related to pheochromocytoma and schizophrenia, and has symptoms including seizures, ptosis and nocturia. An important gene associated with Dopamine Beta-Hydroxylase Deficiency is DBH (Dopamine Beta-Hydroxylase), and among its related pathways/superpathways are Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers and Amino Acid metabolism. The drugs Droxidopa and Antiparkinson Agents have been mentioned in the context of this disorder. Affiliated tissues include eye, testes and heart, and related phenotypes are cardiovascular system and renal/urinary system

UniProtKB/Swiss-Prot : 71 Dopamine beta-hydroxylase deficiency: Characterized by profound deficits in autonomic and cardiovascular function, but apparently only subtle signs, if any, of central nervous system dysfunction.

Genetics Home Reference : 25 Dopamine beta (β)-hydroxylase deficiency is a condition that affects the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. Problems related to this disorder can first appear during infancy. Early signs and symptoms may include episodes of vomiting, dehydration, decreased blood pressure (hypotension), difficulty maintaining body temperature, and low blood sugar (hypoglycemia).

Disease Ontology : 12 An inherited metabolic disorder characterized by decreased beta-hydroxylation of dopamine in nerves resulting in impaired autonomic noradrenergic neurotransmission and clinical features including severely decreased norepinephrine levels, orthostatic hypotension, ptosis, nasal stuffiness, and delayed eye opening that has material basis in homozygous or compound heterozygous mutation in the DBH gene on chromosome 9q34.

Wikipedia : 72 4ZEL... more...

Description from OMIM: 223360
GeneReviews: NBK1474

Related Diseases for Dopamine Beta-Hydroxylase Deficiency

Diseases related to Dopamine Beta-Hydroxylase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 57)
id Related Disease Score Top Affiliating Genes
1 pheochromocytoma 30.8 DBH DDC
2 schizophrenia 11.3
3 attention deficit-hyperactivity disorder 11.2
4 primary orthostatic hypotension 11.2
5 cocaine dependence 11.2
6 migraine with aura 11.2
7 alcohol dependence 11.2
8 gilles de la tourette syndrome 10.9
9 conduct disorder 10.9
10 pure autonomic failure 10.9
11 tuberous sclerosis 10.9
12 menkes disease 10.9
13 cocaine abuse 10.9
14 multiple system atrophy 10.9
15 hereditary dystonia 10.8
16 dysautonomia, familial 10.8
17 orthostatic intolerance 10.8
18 autonomic dysfunction 10.8
19 melanotic neuroectodermal tumor 10.8
20 occipital horn syndrome 10.8
21 oppositional defiant disorder 10.8
22 substance abuse 10.8
23 stuttering 10.8
24 renal hypertension 10.8
25 dystonia-11, myoclonic 10.7
26 diabetic autonomic neuropathy 10.7
27 amyloidosis, hereditary, transthyretin-related 10.7
28 brunner syndrome 10.7
29 postural hypotension 10.7
30 early-onset schizophrenia 10.7
31 psychotic disorder 10.7
32 hypertension, essential 10.7
33 parkinson disease, late-onset 10.7
34 autonomic nervous system disease 10.7
35 neuroblastoma 10.4
36 dysautonomia 10.0
37 repetitive stress injuries 10.0 DBH DDC
38 endogenous depression 9.9
39 pyogenic arthritis, pyoderma gangrenosum and acne 9.9 DBH DDC
40 neuronitis 9.9
41 tardive dyskinesia 9.8
42 post-traumatic stress disorder 9.8
43 bipolar disorder 9.8
44 pathological gambling 9.7
45 epilepsy 9.7
46 autism spectrum disorder 9.7
47 dystonia 9.7
48 neuropathy 9.7
49 learning disability 9.7
50 cervical wilms' tumor 9.6 PAX6 WT1

Graphical network of the top 20 diseases related to Dopamine Beta-Hydroxylase Deficiency:



Diseases related to Dopamine Beta-Hydroxylase Deficiency

Symptoms & Phenotypes for Dopamine Beta-Hydroxylase Deficiency

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Mouth:
high-arched palate

Genitourinary- Bladder:
nocturia

Cardiovascular- Vascular:
orthostatic hypotension, severe, recurrent
fainting spells

Neurologic- Central Nervous System:
seizures may occur during hypotensive episodes

Laboratory- Abnormalities:
undetectable norepinephrine (noradrenaline) in plasma, urine, csf
undetectable epinephrine (adrenaline) in plasma, urine, csf
greatly increased dopamine in plasma, urine, csf (approximately 10-fold increase)
increased plasma dihydroxyphenylacetic acid (dopac)
stimulation of sympathetic fibers results in release of dopamine, not norepinephrine
more
Head And Neck- Eyes:
ptosis
delayed eye opening as a neonate (up to 2 weeks)

Head And Neck- Nose:
nasal stuffiness

Genitourinary- Internal Genitalia Male:
impaired ejaculation due to impaired sympathetic activity
retrograde ejaculation

Metabolic Features:
hypoglycemia, episodic, in infants
hypothermia, episodic, in infants


Clinical features from OMIM:

223360

Human phenotypes related to Dopamine Beta-Hydroxylase Deficiency:

32 (show all 8)
id Description HPO Frequency HPO Source Accession
1 seizures 32 HP:0001250
2 ptosis 32 HP:0000508
3 nocturia 32 HP:0000017
4 high palate 32 HP:0000218
5 orthostatic hypotension 32 HP:0001278
6 neonatal hypoglycemia 32 HP:0001998
7 intermittent hypothermia 32 HP:0005964
8 retrograde ejaculation 32 HP:0012877

UMLS symptoms related to Dopamine Beta-Hydroxylase Deficiency:


nasal congestion (finding)

MGI Mouse Phenotypes related to Dopamine Beta-Hydroxylase Deficiency:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.26 DBH DDC PAX6 WT1
2 renal/urinary system MP:0005367 8.8 DDC PAX6 WT1

Drugs & Therapeutics for Dopamine Beta-Hydroxylase Deficiency

Drugs for Dopamine Beta-Hydroxylase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 75)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Droxidopa Approved, Investigational Phase 4,Phase 3,Phase 1,Phase 2 23651-95-8 443940
2 Antiparkinson Agents Phase 4,Phase 3,Phase 1,Phase 2
3
Dopamine Approved Phase 3,Phase 2,Phase 1 51-61-6, 62-31-7 681
4
Methyldopa Approved Phase 3,Phase 1 555-30-6 38853
5
Metoclopramide Approved, Investigational Phase 3,Phase 1 364-62-5 4168
6
Carbidopa Approved Phase 3,Phase 1,Phase 2 28860-95-9 34359 38101
7
Levodopa Approved Phase 3 59-92-7 6047
8
Mannitol Approved, Investigational Phase 3 69-65-8 453 6251
9 Autonomic Agents Phase 3,Phase 2,Phase 1
10 Dopamine Agents Phase 3,Phase 2,Phase 1
11 Neurotransmitter Agents Phase 3,Phase 2,Phase 1
12 Peripheral Nervous System Agents Phase 3,Phase 2,Phase 1
13 Protective Agents Phase 3,Phase 2,Phase 1
14 Adrenergic Agents Phase 3,Phase 1,Phase 2
15 Adrenergic Agonists Phase 3,Phase 1,Phase 2
16 Adrenergic alpha-2 Receptor Agonists Phase 3,Phase 1
17 Adrenergic alpha-Agonists Phase 3,Phase 1,Phase 2
18 Antiemetics Phase 3,Phase 1
19 Antihypertensive Agents Phase 3,Phase 1
20 Dopamine Antagonists Phase 3,Phase 1
21 Dopamine D2 Receptor Antagonists Phase 3,Phase 1
22 Gastrointestinal Agents Phase 3,Phase 1
23 Neurotransmitter Uptake Inhibitors Phase 3,Phase 1
24 Sympatholytics Phase 3,Phase 1
25 alpha-methyltyrosine Phase 3
26 Aromatic Amino Acid Decarboxylase Inhibitors Phase 3,Phase 1,Phase 2
27 Atomoxetine Hydrochloride Phase 3
28
Entacapone Approved, Investigational Phase 1, Phase 2 130929-57-6 5281081
29
Norepinephrine Approved Phase 1, Phase 2 51-41-2 439260
30 Vasoconstrictor Agents Phase 1, Phase 2
31 Catechol O-Methyltransferase Inhibitors Phase 1, Phase 2
32 Catechol Nutraceutical Phase 1, Phase 2
33
Atropine Approved, Vet_approved Phase 1 5908-99-6, 51-55-8 174174
34
Clonidine Approved Phase 1 4205-90-7 2803
35
Cyclopentolate Approved Phase 1 512-15-2 2905
36
Dipivefrin Approved Phase 1 52365-63-6 3105
37
Edrophonium Approved Phase 1 116-38-1 3202
38
Ephedrine Approved Phase 1 299-42-3 9294
39
Isoproterenol Approved Phase 1 7683-59-2 3779
40
Nitric Oxide Approved Phase 1 10102-43-9 145068
41
Nitroprusside Approved Phase 1 15078-28-1 11963622
42
Oxymetazoline Approved Phase 1 1491-59-4 4636
43
Phenylephrine Approved Phase 1 59-42-7 6041
44
Propranolol Approved, Investigational Phase 1 525-66-6 4946
45
Pseudoephedrine Approved Phase 1 90-82-4 7028
46
Tropicamide Approved Phase 1 1508-75-4 5593
47
Yohimbine Approved, Vet_approved Phase 1 146-48-5 8969
48 Adjuvants, Anesthesia Phase 1
49 Adrenergic alpha-Antagonists Phase 1
50 Adrenergic Antagonists Phase 1

Interventional clinical trials:

(show all 12)

id Name Status NCT ID Phase Drugs
1 Sustained Effect of Droxidopa in Symptomatic Neurogenic Orthostatic Hypotension Recruiting NCT02586623 Phase 4 Droxidopa capsules;Placebo capsules
2 A Clinical Study for Patients With Neurogenic Orthostatic Hypotension (NOH) Using Droxidopa Completed NCT00782340 Phase 3 Placebo;Droxidopa
3 Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH) Completed NCT00633880 Phase 3 Placebo;Droxidopa
4 Open-Label Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH) Completed NCT00738062 Phase 3 Droxidopa;Placebo
5 Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH) (Droxi-304) Completed NCT01132326 Phase 3 Droxidopa
6 Treatment of Orthostatic Hypotension Enrolling by invitation NCT00581477 Phase 3 droxidopa;placebo;alpha-methyldopa;carbidopa;metyrosine;levodopa;atomoxetine;metoclopramide
7 A Clinical Study of Patients With Symptomatic NOH to Assess Sustained Effects of Droxidopa Therapy Terminated NCT01927055 Phase 3 Droxidopa;Placebo
8 Nepicastat for Posttraumatic Stress Disorder (PTSD) in OIF/OEF Veterans Completed NCT00659230 Phase 2 Nepicastat;Placebo
9 Augmenting Effects of L-DOPS With Carbidopa and Entacapone Terminated NCT00547911 Phase 1, Phase 2 Droxidopa;Carbidopa;Entacapone
10 The Pathophysiology of Orthostatic Hypotension Active, not recruiting NCT00748059 Phase 1 phenylephrine,isoproterenol,nitroprusside,propranolol,edrophonium,atropine,tyramine;clonidine,yohimbine,metoclopramide,alpha-methyldopa
11 Long Term Treatment With L-DOPS Approved for marketing NCT00889135 droxidopa
12 A Study to Investigate the Genetic Variation of Dopamine Pathway in Patients With Chronic Pain Recruiting NCT02989792

Search NIH Clinical Center for Dopamine Beta-Hydroxylase Deficiency

Cochrane evidence based reviews: dopamine beta hydroxylase deficiency

Genetic Tests for Dopamine Beta-Hydroxylase Deficiency

Genetic tests related to Dopamine Beta-Hydroxylase Deficiency:

id Genetic test Affiliating Genes
1 Dopamine Beta Hydroxylase Deficiency 29
2 Dopamine Beta-Hydroxylase Deficiency 24 DBH

Anatomical Context for Dopamine Beta-Hydroxylase Deficiency

MalaCards organs/tissues related to Dopamine Beta-Hydroxylase Deficiency:

39
Eye, Testes, Heart, Skin

Publications for Dopamine Beta-Hydroxylase Deficiency

Articles related to Dopamine Beta-Hydroxylase Deficiency:

(show all 25)
id Title Authors Year
1
Mosaic deletion 11p13 in a child with dopamine beta-hydroxylase deficiency--case report and review of the literature. ( 20186791 )
2010
2
Dopamine beta-hydroxylase deficiency. ( 16722595 )
2006
3
Dopamine beta-hydroxylase deficiency involves the central autonomic network. ( 16830134 )
2006
4
Congenital dopamine-beta-hydroxylase deficiency in humans. ( 15240410 )
2004
5
[From gene to disease; dopamine-beta-hydroxylase deficiency and orthostatic hypotension]. ( 15495941 )
2004
6
Peripartum management of a patient with dopamine beta-hydroxylase deficiency, a rare congenital cause of dysautonomia. ( 12180590 )
2002
7
Dopamine beta-hydroxylase deficiency impairs cellular immunity. ( 10051631 )
1999
8
The sympathetic skin response in peripheral autonomic failure--evaluation in pure failure, pure cholinergic dysautonomia and dopamine-beta-hydroxylase deficiency. ( 9651662 )
1998
9
Dopamine beta-hydroxylase deficiency associated with mutations in a copper transporter gene. ( 9327848 )
1998
10
Total norepinephrine spillover, muscle sympathetic nerve activity and heart-rate spectral analysis in a patient with dopamine beta-hydroxylase deficiency. ( 8801271 )
1995
11
Dopamine beta-hydroxylase immunoreactivity in human cerebrospinal fluid: properties, relationship to central noradrenergic neuronal activity and variation in Parkinson's disease and congenital dopamine beta-hydroxylase deficiency. ( 8143425 )
1994
12
Dopamine Beta-Hydroxylase Deficiency ( 20301647 )
1993
13
Sleeping with and without norepinephrine: effects of metoclopramide and D,L-threo-3,4-dihydroxyphenylserine on sleep in dopamine beta-hydroxylase deficiency. ( 1811317 )
1991
14
Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation. ( 1677640 )
1991
15
Dopamine-beta-hydroxylase deficiency in humans. ( 2300263 )
1990
16
D,L-threo-3, 4-DOPS enhances rapid eye movement sleep in patients with congenital dopamine beta-hydroxylase deficiency. ( 2155257 )
1990
17
Sleep patterns in congenital dopamine beta-hydroxylase deficiency. ( 2355243 )
1990
18
Reflex control of sympathetic nerve activity in dopamine beta-hydroxylase deficiency. ( 2295511 )
1990
19
Patients with congenital dopamine beta-hydroxylase deficiency. A lesson in catecholamine physiology. ( 3291893 )
1988
20
d,l-threo-3,4-dihydroxyphenylserine restores sympathetic control and cures orthostatic hypotension in dopamine beta-hydroxylase deficiency. ( 3149290 )
1988
21
Effect of unnatural noradrenaline precursor on sympathetic control and orthostatic hypotension in dopamine-beta-hydroxylase deficiency. ( 2890807 )
1987
22
Endogenous restoration of noradrenaline by precursor therapy in dopamine-beta-hydroxylase deficiency. ( 2890806 )
1987
23
Dopamine in dopamine-beta-hydroxylase deficiency. ( 3683474 )
1987
24
Congenital dopamine beta-hydroxylase deficiency. ( 2882120 )
1987
25
Congenital dopamine-beta-hydroxylase deficiency. A novel orthostatic syndrome. ( 2880016 )
1987

Variations for Dopamine Beta-Hydroxylase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Dopamine Beta-Hydroxylase Deficiency:

71
id Symbol AA change Variation ID SNP ID
1 DBH p.Val101Met VAR_022758 rs267606760
2 DBH p.Asp114Glu VAR_022759 rs77576840
3 DBH p.Asp345Asn VAR_022760 rs267606761

ClinVar genetic disease variations for Dopamine Beta-Hydroxylase Deficiency:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 DBH NM_000787.3(DBH): c.339+2T> C single nucleotide variant Pathogenic rs74853476 GRCh37 Chromosome 9, 136501834: 136501834
2 DBH NM_000787.3(DBH): c.342C> A (p.Asp114Glu) single nucleotide variant Pathogenic rs77576840 GRCh37 Chromosome 9, 136504970: 136504970
3 DBH NM_000787.3(DBH): c.301G> A (p.Val101Met) single nucleotide variant Pathogenic rs267606760 GRCh37 Chromosome 9, 136501794: 136501794
4 DBH NM_000787.3(DBH): c.1033G> A (p.Asp345Asn) single nucleotide variant Pathogenic rs267606761 GRCh37 Chromosome 9, 136512976: 136512976
5 DBH NM_000787.3(DBH): c.617delA (p.Glu206Glyfs) deletion Pathogenic rs863225244 GRCh37 Chromosome 9, 136507459: 136507459
6 DBH NM_000787.3(DBH): c.806G> T (p.Cys269Phe) single nucleotide variant Pathogenic rs863225245 GRCh37 Chromosome 9, 136508596: 136508596
7 DBH NM_000787.3(DBH): c.1085C> A (p.Ala362Glu) single nucleotide variant Pathogenic rs75215331 GRCh37 Chromosome 9, 136513028: 136513028
8 DBH NM_000787.3(DBH): c.1667A> G (p.Tyr556Cys) single nucleotide variant Pathogenic rs863225246 GRCh38 Chromosome 9, 133657174: 133657174

Expression for Dopamine Beta-Hydroxylase Deficiency

Search GEO for disease gene expression data for Dopamine Beta-Hydroxylase Deficiency.

Pathways for Dopamine Beta-Hydroxylase Deficiency

GO Terms for Dopamine Beta-Hydroxylase Deficiency

Biological processes related to Dopamine Beta-Hydroxylase Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 glucose homeostasis GO:0042593 9.16 DBH PAX6
2 camera-type eye development GO:0043010 8.96 PAX6 WT1
3 catecholamine biosynthetic process GO:0042423 8.62 DBH DDC

Molecular functions related to Dopamine Beta-Hydroxylase Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 transcription regulatory region DNA binding GO:0044212 8.62 PAX6 WT1

Sources for Dopamine Beta-Hydroxylase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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