DBH DEFICIENCY
MCID: ORT011
MIFTS: 33

Orthostatic Hypotension 1 (DBH DEFICIENCY)

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

Aliases & Classifications for Orthostatic Hypotension 1

MalaCards integrated aliases for Orthostatic Hypotension 1:

Name: Orthostatic Hypotension 1 58
Norepinephrine Deficiency 58 60 76
Noradrenaline Deficiency 58 60 76
Dopamine Beta-Hydroxylase Deficiency 60 76
Dopamine Beta-Hydroxylase Deficiency, Congenital 58
Orthostatic Hypotension 1, Due to Dbh Deficiency 58
Dbh Deficiency 76
Orthyp1 58

Characteristics:

Orphanet epidemiological data:

60
dopamine beta-hydroxylase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal recessive


HPO:

33
orthostatic hypotension 1:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 58 223360
MESH via Orphanet 46 C535600
ICD10 via Orphanet 35 G90.8
UMLS via Orphanet 75 C0342687
Orphanet 60 ORPHA230

Summaries for Orthostatic Hypotension 1

UniProtKB/Swiss-Prot : 76 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.

MalaCards based summary : Orthostatic Hypotension 1, also known as norepinephrine deficiency, is related to dopamine beta-hydroxylase deficiency and orthostatic hypotension 2. An important gene associated with Orthostatic Hypotension 1 is DBH (Dopamine Beta-Hydroxylase). The drugs Dopamine and Droxidopa have been mentioned in the context of this disorder. Affiliated tissues include eye, and related phenotypes are high palate and ptosis

Description from OMIM: 223360

Related Diseases for Orthostatic Hypotension 1

Diseases in the Primary Orthostatic Hypotension family:

Orthostatic Hypotension 1 Orthostatic Hypotension 2

Diseases related to Orthostatic Hypotension 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 dopamine beta-hydroxylase deficiency 12.0
2 orthostatic hypotension 2 11.2
3 dysautonomia 10.2
4 insensitivity to pain, congenital, with anhidrosis 9.7
5 aging 9.7
6 neuropathy, hereditary sensory and autonomic, type v 9.7
7 anhidrosis 9.7
8 primary orthostatic hypotension 9.7
9 pure autonomic failure 9.7

Graphical network of the top 20 diseases related to Orthostatic Hypotension 1:



Diseases related to Orthostatic Hypotension 1

Symptoms & Phenotypes for Orthostatic Hypotension 1

Human phenotypes related to Orthostatic Hypotension 1:

33 (show all 8)
# Description HPO Frequency HPO Source Accession
1 high palate 33 HP:0000218
2 ptosis 33 HP:0000508
3 seizures 33 HP:0001250
4 neonatal hypoglycemia 33 HP:0001998
5 orthostatic hypotension 33 HP:0001278
6 nocturia 33 HP:0000017
7 retrograde ejaculation 33 HP:0012877
8 intermittent hypothermia 33 HP:0005964

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
ptosis
delayed eye opening as a neonate (up to 2 weeks)

Head And Neck Mouth:
high-arched palate

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
Genitourinary Bladder:
nocturia

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

Drugs & Therapeutics for Orthostatic Hypotension 1

Drugs for Orthostatic Hypotension 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 76)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dopamine Approved Phase 3,Phase 2,Phase 1,Not Applicable 62-31-7, 51-61-6 681
2
Droxidopa Approved, Investigational Phase 3,Phase 1,Phase 2 23651-95-8 443940
3
Metoclopramide Approved, Investigational Phase 3,Phase 1 364-62-5 4168
4
Methyldopa Approved Phase 3,Phase 1 555-30-6 38853
5
Carbidopa Approved Phase 3,Phase 1,Phase 2 28860-95-9 34359
6
Levodopa Approved Phase 3 59-92-7 6047
7
Mannitol Approved, Investigational Phase 3 69-65-8 453 6251
8 Antiparkinson Agents Phase 3,Phase 1,Phase 2
9 Autonomic Agents Phase 3,Phase 2,Phase 1,Not Applicable
10 Neurotransmitter Agents Phase 3,Phase 2,Phase 1,Not Applicable
11 Sympathomimetics Phase 3,Phase 2,Phase 1,Not Applicable
12 Peripheral Nervous System Agents Phase 3,Phase 2,Phase 1,Not Applicable
13 Dopamine Agents Phase 3,Phase 2,Phase 1,Not Applicable
14 Cardiotonic Agents Phase 3,Phase 2,Phase 1,Not Applicable
15 Protective Agents Phase 3,Phase 2,Phase 1,Not Applicable
16 Dopamine Antagonists Phase 3,Phase 1
17 Gastrointestinal Agents Phase 3,Phase 1
18 Antihypertensive Agents Phase 3,Phase 1
19 Adrenergic alpha-Agonists Phase 3,Phase 1,Phase 2
20 Antiemetics Phase 3,Phase 1
21 Adrenergic Agents Phase 3,Phase 1,Phase 2
22 Neurotransmitter Uptake Inhibitors Phase 3,Phase 1
23 Dopamine D2 Receptor Antagonists Phase 3,Phase 1
24 Adrenergic alpha-2 Receptor Agonists Phase 3,Phase 1
25 Sympatholytics Phase 3,Phase 1
26 Adrenergic Agonists Phase 3,Phase 1,Phase 2
27 alpha-methyltyrosine Phase 3
28 Aromatic Amino Acid Decarboxylase Inhibitors Phase 3,Phase 1,Phase 2
29 Atomoxetine Hydrochloride Phase 3
30
Entacapone Approved, Investigational Phase 1, Phase 2 130929-57-6 5281081
31
Norepinephrine Approved Phase 1, Phase 2 51-41-2 439260
32 Vasoconstrictor Agents Phase 1, Phase 2
33 Catechol Phase 1, Phase 2
34 Catechol O-Methyltransferase Inhibitors Phase 1, Phase 2
35
Clonidine Approved Phase 1 4205-90-7 2803
36
Dipivefrin Approved Phase 1 52365-63-6 3105
37
Ephedrine Approved Phase 1 299-42-3 9294
38
Propranolol Approved, Investigational Phase 1 525-66-6 4946
39
Isoproterenol Approved, Investigational Phase 1 7683-59-2 3779
40
Phenylephrine Approved Phase 1 59-42-7 6041
41
Yohimbine Approved, Investigational, Vet_approved Phase 1 146-48-5 8969
42
Nitric Oxide Approved Phase 1 10102-43-9 145068
43
Edrophonium Approved Phase 1 116-38-1, 312-48-1 3202
44
Nitroprusside Approved, Investigational Phase 1 15078-28-1 11963622
45
Oxymetazoline Approved, Investigational Phase 1 1491-59-4 4636
46
Tropicamide Approved, Investigational Phase 1 1508-75-4 5593
47
Atropine Approved, Vet_approved Phase 1 51-55-8, 5908-99-6 174174
48
Cyclopentolate Approved Phase 1 512-15-2 2905
49
Pseudoephedrine Approved Phase 1 90-82-4 7028
50 Yohimbe Phase 1

Interventional clinical trials:


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

Search NIH Clinical Center for Orthostatic Hypotension 1

Genetic Tests for Orthostatic Hypotension 1

Anatomical Context for Orthostatic Hypotension 1

MalaCards organs/tissues related to Orthostatic Hypotension 1:

42
Eye

Publications for Orthostatic Hypotension 1

Articles related to Orthostatic Hypotension 1:

# Title Authors Year
1
Norepinephrine deficiency with normal blood pressure control in congenital insensitivity to pain with anhidrosis. ( 25627679 )
2015
2
Aging-associated formaldehyde-induced norepinephrine deficiency contributes to age-related memory decline. ( 25866202 )
2015
3
Neurogenic orthostatic hypotension: roles of norepinephrine deficiency in its causes, its treatment, and future research directions. ( 26373628 )
2015
4
Norepinephrine deficiency in Parkinson's disease: the case for noradrenergic enhancement. ( 25297066 )
2014
5
Norepinephrine deficiency is caused by combined abnormal mRNA processing and defective protein trafficking of dopamine beta-hydroxylase. ( 21209083 )
2011
6
Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiency. ( 11857564 )
2002
7
Mice with chronic norepinephrine deficiency resemble amphetamine-sensitized animals. ( 12370425 )
2002
8
Evidence suggesting the role of norepinephrine deficiency in late stages of Parkinson's disease. ( 10410763 )
1999
9
Norepinephrine deficiency and behavioral senescence in aged rats. Transplanted locus ceruleus neurons as an experimental replacement therapy. ( 3474952 )
1987

Variations for Orthostatic Hypotension 1

UniProtKB/Swiss-Prot genetic disease variations for Orthostatic Hypotension 1:

76
# 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 Orthostatic Hypotension 1:

6 (show top 50) (show all 168)
# Gene Variation Type Significance SNP ID Assembly Location
1 DBH NG_008645.1: g.386_387(11_15) NT expansion Benign rs72191426 GRCh37 Chromosome 9, 136496870: 136496871
2 DBH NG_008645.1: g.386_387(11_15) NT expansion Benign rs72191426 GRCh38 Chromosome 9, 133631748: 133631749
3 DBH NM_000787.3(DBH): c.-979T> C single nucleotide variant Benign rs1611115 GRCh37 Chromosome 9, 136500515: 136500515
4 DBH NM_000787.3(DBH): c.-979T> C single nucleotide variant Benign rs1611115 GRCh38 Chromosome 9, 133635393: 133635393
5 DBH NM_000787.3(DBH): c.486A> G (p.Glu162=) single nucleotide variant Benign rs1108580 GRCh38 Chromosome 9, 133639992: 133639992
6 DBH NM_000787.3(DBH): c.486A> G (p.Glu162=) single nucleotide variant Benign rs1108580 GRCh37 Chromosome 9, 136505114: 136505114
7 DBH NM_000787.3(DBH): c.617delA (p.Glu206Glyfs) deletion Pathogenic rs863225244 GRCh37 Chromosome 9, 136507459: 136507459
8 DBH NM_000787.3(DBH): c.617delA (p.Glu206Glyfs) deletion Pathogenic rs863225244 GRCh38 Chromosome 9, 133642337: 133642337
9 DBH NM_000787.3(DBH): c.806G> T (p.Cys269Phe) single nucleotide variant Pathogenic rs863225245 GRCh37 Chromosome 9, 136508596: 136508596
10 DBH NM_000787.3(DBH): c.806G> T (p.Cys269Phe) single nucleotide variant Pathogenic rs863225245 GRCh38 Chromosome 9, 133643474: 133643474
11 DBH NM_000787.3(DBH): c.1085C> A (p.Ala362Glu) single nucleotide variant Pathogenic rs75215331 GRCh37 Chromosome 9, 136513028: 136513028
12 DBH NM_000787.3(DBH): c.1085C> A (p.Ala362Glu) single nucleotide variant Pathogenic rs75215331 GRCh38 Chromosome 9, 133647906: 133647906
13 DBH NM_000787.3(DBH): c.1667A> G (p.Tyr556Cys) single nucleotide variant Pathogenic rs863225246 GRCh38 Chromosome 9, 133657174: 133657174
14 DBH NM_000787.3(DBH): c.1667A> G (p.Tyr556Cys) single nucleotide variant Pathogenic rs863225246 GRCh37 Chromosome 9, 136522296: 136522296
15 DBH NM_000787.3(DBH): c.339+2T> C single nucleotide variant Pathogenic rs74853476 GRCh37 Chromosome 9, 136501834: 136501834
16 DBH NM_000787.3(DBH): c.339+2T> C single nucleotide variant Pathogenic rs74853476 GRCh38 Chromosome 9, 133636712: 133636712
17 DBH NM_000787.3(DBH): c.342C> A (p.Asp114Glu) single nucleotide variant Pathogenic rs77576840 GRCh37 Chromosome 9, 136504970: 136504970
18 DBH NM_000787.3(DBH): c.342C> A (p.Asp114Glu) single nucleotide variant Pathogenic rs77576840 GRCh38 Chromosome 9, 133639848: 133639848
19 DBH NM_000787.3(DBH): c.301G> A (p.Val101Met) single nucleotide variant Pathogenic rs267606760 GRCh37 Chromosome 9, 136501794: 136501794
20 DBH NM_000787.3(DBH): c.301G> A (p.Val101Met) single nucleotide variant Pathogenic rs267606760 GRCh38 Chromosome 9, 133636672: 133636672
21 DBH NM_000787.3(DBH): c.1033G> A (p.Asp345Asn) single nucleotide variant Pathogenic rs267606761 GRCh37 Chromosome 9, 136512976: 136512976
22 DBH NM_000787.3(DBH): c.1033G> A (p.Asp345Asn) single nucleotide variant Pathogenic rs267606761 GRCh38 Chromosome 9, 133647854: 133647854
23 DBH 19-bp insertion/deletion indel Benign
24 DBH MspI polymorphic site in intron 9 undetermined variant Benign
25 DBH NM_000787.3(DBH): c.602A> G (p.Asn201Ser) single nucleotide variant Likely benign rs45465204 GRCh38 Chromosome 9, 133642322: 133642322
26 DBH NM_000787.3(DBH): c.602A> G (p.Asn201Ser) single nucleotide variant Likely benign rs45465204 GRCh37 Chromosome 9, 136507444: 136507444
27 DBH NM_000787.3(DBH): c.407T> C (p.Val136Ala) single nucleotide variant Uncertain significance rs886063657 GRCh38 Chromosome 9, 133639913: 133639913
28 DBH NM_000787.3(DBH): c.407T> C (p.Val136Ala) single nucleotide variant Uncertain significance rs886063657 GRCh37 Chromosome 9, 136505035: 136505035
29 DBH NM_000787.3(DBH): c.486+13C> T single nucleotide variant Likely benign rs1611119 GRCh38 Chromosome 9, 133640005: 133640005
30 DBH NM_000787.3(DBH): c.486+13C> T single nucleotide variant Likely benign rs1611119 GRCh37 Chromosome 9, 136505127: 136505127
31 DBH NM_000787.3(DBH): c.631G> A (p.Ala211Thr) single nucleotide variant Likely benign rs5320 GRCh38 Chromosome 9, 133642351: 133642351
32 DBH NM_000787.3(DBH): c.631G> A (p.Ala211Thr) single nucleotide variant Likely benign rs5320 GRCh37 Chromosome 9, 136507473: 136507473
33 DBH NM_000787.3(DBH): c.735C> T (p.His245=) single nucleotide variant Likely benign rs5322 GRCh38 Chromosome 9, 133642455: 133642455
34 DBH NM_000787.3(DBH): c.735C> T (p.His245=) single nucleotide variant Likely benign rs5322 GRCh37 Chromosome 9, 136507577: 136507577
35 DBH NM_000787.3(DBH): c.852C> T (p.Asp284=) single nucleotide variant Uncertain significance rs886063658 GRCh37 Chromosome 9, 136508642: 136508642
36 DBH NM_000787.3(DBH): c.852C> T (p.Asp284=) single nucleotide variant Uncertain significance rs886063658 GRCh38 Chromosome 9, 133643520: 133643520
37 DBH NM_000787.3(DBH): c.1094T> C (p.Met365Thr) single nucleotide variant Uncertain significance rs200103371 GRCh37 Chromosome 9, 136513037: 136513037
38 DBH NM_000787.3(DBH): c.1094T> C (p.Met365Thr) single nucleotide variant Uncertain significance rs200103371 GRCh38 Chromosome 9, 133647915: 133647915
39 DBH NM_000787.3(DBH): c.1139G> A (p.Arg380Gln) single nucleotide variant Uncertain significance rs77984399 GRCh37 Chromosome 9, 136513082: 136513082
40 DBH NM_000787.3(DBH): c.1139G> A (p.Arg380Gln) single nucleotide variant Uncertain significance rs77984399 GRCh38 Chromosome 9, 133647960: 133647960
41 DBH NM_000787.3(DBH): c.1173G> A (p.Thr391=) single nucleotide variant Uncertain significance rs201689325 GRCh37 Chromosome 9, 136513116: 136513116
42 DBH NM_000787.3(DBH): c.1173G> A (p.Thr391=) single nucleotide variant Uncertain significance rs201689325 GRCh38 Chromosome 9, 133647994: 133647994
43 DBH NM_000787.3(DBH): c.1572C> T (p.Asn524=) single nucleotide variant Uncertain significance rs200509113 GRCh38 Chromosome 9, 133657079: 133657079
44 DBH NM_000787.3(DBH): c.1572C> T (p.Asn524=) single nucleotide variant Uncertain significance rs200509113 GRCh37 Chromosome 9, 136522201: 136522201
45 DBH NM_000787.3(DBH): c.1722+4C> T single nucleotide variant Uncertain significance rs45532436 GRCh38 Chromosome 9, 133657233: 133657233
46 DBH NM_000787.3(DBH): c.1722+4C> T single nucleotide variant Uncertain significance rs45532436 GRCh37 Chromosome 9, 136522355: 136522355
47 DBH NM_000787.3(DBH): c.1734C> T (p.Asn578=) single nucleotide variant Conflicting interpretations of pathogenicity rs45446891 GRCh38 Chromosome 9, 133658327: 133658327
48 DBH NM_000787.3(DBH): c.1734C> T (p.Asn578=) single nucleotide variant Conflicting interpretations of pathogenicity rs45446891 GRCh37 Chromosome 9, 136523449: 136523449
49 DBH NM_000787.3(DBH): c.*431C> T single nucleotide variant Uncertain significance rs551208345 GRCh37 Chromosome 9, 136524000: 136524000
50 DBH NM_000787.3(DBH): c.*431C> T single nucleotide variant Uncertain significance rs551208345 GRCh38 Chromosome 9, 133658878: 133658878

Expression for Orthostatic Hypotension 1

Search GEO for disease gene expression data for Orthostatic Hypotension 1.

Pathways for Orthostatic Hypotension 1

GO Terms for Orthostatic Hypotension 1

Sources for Orthostatic Hypotension 1

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