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Orthostatic hypotension 1(ORTHYP1)

MedGen UID:
1648402
Concept ID:
C4746777
Disease or Syndrome
Synonyms: Dopamine beta-hydroxylase deficiency; Dopamine beta-hydroxylase deficiency, congenital; Noradrenaline deficiency; Norepinephrine deficiency; Orthostatic hypotension 1, due to DBH deficiency; ORTHYP1
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): DBH (9q34.2)
 
Monarch Initiative: MONDO:0009123
OMIM®: 223360
Orphanet: ORPHA230

Disease characteristics

Excerpted from the GeneReview: Dopamine Beta-Hydroxylase Deficiency
Dopamine beta-hydroxylase (DBH) deficiency is characterized by lack of sympathetic noradrenergic function resulting in profound deficits in autonomic regulation of cardiovascular function (orthostatic hypotension) and other autonomic dysfunction (ptosis, nasal stuffiness, sleep difficulties, and impaired ejaculation in males). Although DBH deficiency is present from birth, the diagnosis is often not generally recognized until late childhood. In the perinatal period, DBH deficiency has been complicated by vomiting, dehydration, hypotension, hypothermia, and hypoglycemia requiring repeated hospitalization, and the diagnosis may be identified fortuitously in the neonatal period with investigation of hypoglycemia. Children may report reduced exercise capacity. By early adulthood, individuals have profound orthostatic hypotension, greatly reduced exercise tolerance, ptosis, and nasal stuffiness. Presyncopal symptoms include dizziness, blurred vision, dyspnea, nuchal discomfort, and chest pain; symptoms may worsen in hot environments or after heavy meals or alcohol ingestion. Some individuals have abnormal kidney function, joint laxity, hypotonia, high-arched palate, anemia, and/or hypoglycemia. [from GeneReviews]
Authors:
Italo Biaggioni   view full author information

Additional descriptions

From OMIM
Orthostatic hypotension-1 (ORTHYP1) is an autosomal recessive disorder characterized by profound autonomic failure. In addition to severe orthostatic hypotension, ptosis, nasal stuffiness, impaired ejaculation, and a neonatal history of delayed eye opening are frequent findings. Biochemical features include undetectable tissue and circulating levels of norepinephrine and epinephrine, elevated levels of dopamine, and undetectable levels of dopamine beta-hydroxylase (summary by Kim et al., 2002). Genetic Heterogeneity of Orthostatic Hypotension See also ORTHYP2 (618182), caused by mutation in the CYB561 gene (600019) on chromosome 17q23.  http://www.omim.org/entry/223360
From MedlinePlus Genetics
Dopamine beta-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. The signs and symptoms of dopamine beta-hydroxylase deficiency are caused by a lack of norepinephrine, one of the main chemical messengers (neurotransmitters) of the autonomic nervous system.

Although the signs and symptoms of dopamine beta-hydroxylase deficiency can appear during infancy, people often do not receive a diagnosis until their symptoms worsen during adolescence. Early signs and symptoms may include droopy eyelids (ptosis) and low blood pressure (hypotension). Infants with dopamine beta-hydroxylase deficiency may also experience vomiting, dehydration, decreased body temperature, and low blood glucose (hypoglycemia), which may lead to frequent hospitalizations.

By adolescence or early adulthood, people with dopamine beta-hydroxylase deficiency often have a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. Affected individuals typically experience extreme fatigue during exercise (exercise intolerance) due to their problems maintaining a normal blood pressure.

Other features of dopamine beta-hydroxylase deficiency include nasal congestion, an inability to stand for a prolonged period of time, and retrograde ejaculation, which is a discharge of semen backwards into the bladder.

Symptoms of dopamine beta-hydroxylase deficiency may improve with treatment. If the condition is not treated, symptoms often worsen during adolescence.

  https://medlineplus.gov/genetics/condition/dopamine-beta-hydroxylase-deficiency

Clinical features

From HPO
Nocturia
MedGen UID:
14440
Concept ID:
C0028734
Disease or Syndrome
Abnormally increased production of urine during the night leading to an unusually frequent need to urinate.
Retrograde ejaculation
MedGen UID:
98338
Concept ID:
C0403673
Pathologic Function
The emission of semen and seminal fluid into the bladder instead of through the penis during orgasm.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Atrial fibrillation
MedGen UID:
445
Concept ID:
C0004238
Finding
An atrial arrhythmia characterized by disorganized atrial activity without discrete P waves on the surface EKG, but instead by an undulating baseline or more sharply circumscribed atrial deflections of varying amplitude an frequency ranging from 350 to 600 per minute.
Orthostatic hypotension
MedGen UID:
43803
Concept ID:
C0020651
Disease or Syndrome
A form of hypotension characterized by a sudden fall in blood pressure that occurs when a person assumes a standing position.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Isolated prolactin deficiency
MedGen UID:
75758
Concept ID:
C0271586
Finding
A reduced level of prolactin in the blood circulation. Prolactin is a protein hormone that is secreted by lactotrophs in the anterior pituitary and that stimulates mammary gland development and milk production.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Weakness of facial musculature
MedGen UID:
98103
Concept ID:
C0427055
Disease or Syndrome
Reduced strength of one or more muscles innervated by the facial nerve (the seventh cranial nerve).
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Increased blood urea nitrogen
MedGen UID:
760252
Concept ID:
C0151539
Finding
An increased amount of nitrogen in the form of urea in the blood.
Hypomagnesemia
MedGen UID:
57481
Concept ID:
C0151723
Disease or Syndrome
An abnormally decreased magnesium concentration in the blood.
Neonatal hypoglycemia
MedGen UID:
57646
Concept ID:
C0158986
Finding
Blood glucose concentration below the lower limit of established reference ranges in a newborn.
Intermittent hypothermia
MedGen UID:
332504
Concept ID:
C1837639
Finding
Episodes of reduced body temperature.
Elevated circulating dihydroxyphenylacetic acid concentration
MedGen UID:
1054866
Concept ID:
CN376747
Finding
The concentration of dihydroxyphenylacetic acid in the blood circulation is above the upper limit of normal.
Reduced circulating dopamine beta-hydroxylase activity
MedGen UID:
1054214
Concept ID:
CN377388
Finding
Concentration of Dopamine beta-hydroxylase (DBH; EC 1.14.17.1) in the blood circulation below the lower limit of normal. DBH catalyzes the oxidative hydroxylation of dopamine to norepinephrine.
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.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
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).
Lack of pupillary response to hydroxyamphetamine
MedGen UID:
1054596
Concept ID:
CN378346
Finding
4-hydroxyamphetamine is used in eye drops to dilate the pupil, e.g.., to induce mydriasis for fundus examinations. This term refers to a lack of response of the pupil to topical application of 4-hydroxyamphetamine.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVOrthostatic hypotension 1

Professional guidelines

PubMed

Reddin C, Murphy R, Hanrahan C, Loughlin E, Ferguson J, Judge C, Waters R, Canavan M, Kenny RA, O'Donnell M
Age Ageing 2023 Apr 1;52(4) doi: 10.1093/ageing/afad044. PMID: 37014001Free PMC Article
Ferreira Neto CJ, Rocha AS, Schmidt L, de Almeida FP, Dutra JC, da Rocha MD
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Mostile G, Jankovic J
Parkinsonism Relat Disord 2009 Dec;15 Suppl 3:S224-32. doi: 10.1016/S1353-8020(09)70820-X. PMID: 20082997

Recent clinical studies

Etiology

Vidal-Petiot E, Pathak A, Azulay JP, Pavy-Le Traon A, Hanon O
Rev Neurol (Paris) 2024 Jan-Feb;180(1-2):53-64. Epub 2023 Dec 19 doi: 10.1016/j.neurol.2023.11.001. PMID: 38123372
Juraschek SP, Hu JR, Cluett JL, Ishak AM, Mita C, Lipsitz LA, Appel LJ, Beckett NS, Coleman RL, Cushman WC, Davis BR, Grandits G, Holman RR, Miller ER 3rd, Peters R, Staessen JA, Taylor AA, Thijs L, Wright JT Jr, Mukamal KJ
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Kim MJ, Farrell J
Am Fam Physician 2022 Jan 1;105(1):39-49. PMID: 35029940
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J Am Med Dir Assoc 2019 May;20(5):589-597.e5. Epub 2018 Dec 21 doi: 10.1016/j.jamda.2018.11.003. PMID: 30583909

Diagnosis

Vidal-Petiot E, Pathak A, Azulay JP, Pavy-Le Traon A, Hanon O
Rev Neurol (Paris) 2024 Jan-Feb;180(1-2):53-64. Epub 2023 Dec 19 doi: 10.1016/j.neurol.2023.11.001. PMID: 38123372
Juraschek SP, Hu JR, Cluett JL, Ishak AM, Mita C, Lipsitz LA, Appel LJ, Beckett NS, Coleman RL, Cushman WC, Davis BR, Grandits G, Holman RR, Miller ER 3rd, Peters R, Staessen JA, Taylor AA, Thijs L, Wright JT Jr, Mukamal KJ
JAMA 2023 Oct 17;330(15):1459-1471. doi: 10.1001/jama.2023.18497. PMID: 37847274Free PMC Article
Kim MJ, Farrell J
Am Fam Physician 2022 Jan 1;105(1):39-49. PMID: 35029940
Palma JA, Kaufmann H
Continuum (Minneap Minn) 2020 Feb;26(1):154-177. doi: 10.1212/CON.0000000000000816. PMID: 31996627Free PMC Article
Kim HA, Bisdorff A, Bronstein AM, Lempert T, Rossi-Izquierdo M, Staab JP, Strupp M, Kim JS
J Vestib Res 2019;29(2-3):45-56. doi: 10.3233/VES-190655. PMID: 30883381Free PMC Article

Therapy

Vidal-Petiot E, Pathak A, Azulay JP, Pavy-Le Traon A, Hanon O
Rev Neurol (Paris) 2024 Jan-Feb;180(1-2):53-64. Epub 2023 Dec 19 doi: 10.1016/j.neurol.2023.11.001. PMID: 38123372
Juraschek SP, Hu JR, Cluett JL, Ishak AM, Mita C, Lipsitz LA, Appel LJ, Beckett NS, Coleman RL, Cushman WC, Davis BR, Grandits G, Holman RR, Miller ER 3rd, Peters R, Staessen JA, Taylor AA, Thijs L, Wright JT Jr, Mukamal KJ
JAMA 2023 Oct 17;330(15):1459-1471. doi: 10.1001/jama.2023.18497. PMID: 37847274Free PMC Article
Kim MJ, Farrell J
Am Fam Physician 2022 Jan 1;105(1):39-49. PMID: 35029940
Yu JT, Xu W, Tan CC, Andrieu S, Suckling J, Evangelou E, Pan A, Zhang C, Jia J, Feng L, Kua EH, Wang YJ, Wang HF, Tan MS, Li JQ, Hou XH, Wan Y, Tan L, Mok V, Tan L, Dong Q, Touchon J, Gauthier S, Aisen PS, Vellas B
J Neurol Neurosurg Psychiatry 2020 Nov;91(11):1201-1209. Epub 2020 Jul 20 doi: 10.1136/jnnp-2019-321913. PMID: 32690803Free PMC Article
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Prognosis

Petriceks AH, Appel LJ, Miller ER 3rd, Mitchell CM, Schrack JA, Mukamal KJ, Lipsitz LA, Wanigatunga AA, Plante TB, Michos ED, Juraschek SP
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Didangelos T, Karlafti E, Kotzakioulafi E, Margariti E, Giannoulaki P, Batanis G, Tesfaye S, Kantartzis K
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Am Fam Physician 2017 Mar 1;95(5):303-312. PMID: 28290647

Clinical prediction guides

Petriceks AH, Appel LJ, Miller ER 3rd, Mitchell CM, Schrack JA, Mukamal KJ, Lipsitz LA, Wanigatunga AA, Plante TB, Michos ED, Juraschek SP
J Am Geriatr Soc 2023 Dec;71(12):3711-3720. Epub 2023 Sep 5 doi: 10.1111/jgs.18573. PMID: 37668347Free PMC Article
Veazie S, Peterson K, Ansari Y, Chung KA, Gibbons CH, Raj SR, Helfand M
Cochrane Database Syst Rev 2021 May 17;5(5):CD012868. doi: 10.1002/14651858.CD012868.pub2. PMID: 34000076Free PMC Article
Hale GM, Valdes J, Brenner M
Ann Pharmacother 2017 May;51(5):417-428. Epub 2017 Jan 16 doi: 10.1177/1060028016689264. PMID: 28092986
Kaufmann H, Malamut R, Norcliffe-Kaufmann L, Rosa K, Freeman R
Clin Auton Res 2012 Apr;22(2):79-90. Epub 2011 Nov 2 doi: 10.1007/s10286-011-0146-2. PMID: 22045363
Lagi A, Spini S
Clin Cardiol 2010 Jun;33(6):E10-5. doi: 10.1002/clc.20722. PMID: 20552588Free PMC Article

Recent systematic reviews

Juraschek SP, Hu JR, Cluett JL, Ishak AM, Mita C, Lipsitz LA, Appel LJ, Beckett NS, Coleman RL, Cushman WC, Davis BR, Grandits G, Holman RR, Miller ER 3rd, Peters R, Staessen JA, Taylor AA, Thijs L, Wright JT Jr, Mukamal KJ
JAMA 2023 Oct 17;330(15):1459-1471. doi: 10.1001/jama.2023.18497. PMID: 37847274Free PMC Article
D'Antona L, Jaime Merchan MA, Vassiliou A, Watkins LD, Davagnanam I, Toma AK, Matharu MS
JAMA Neurol 2021 Mar 1;78(3):329-337. doi: 10.1001/jamaneurol.2020.4799. PMID: 33393980Free PMC Article
Yu JT, Xu W, Tan CC, Andrieu S, Suckling J, Evangelou E, Pan A, Zhang C, Jia J, Feng L, Kua EH, Wang YJ, Wang HF, Tan MS, Li JQ, Hou XH, Wan Y, Tan L, Mok V, Tan L, Dong Q, Touchon J, Gauthier S, Aisen PS, Vellas B
J Neurol Neurosurg Psychiatry 2020 Nov;91(11):1201-1209. Epub 2020 Jul 20 doi: 10.1136/jnnp-2019-321913. PMID: 32690803Free PMC Article
Ou YN, Tan CC, Shen XN, Xu W, Hou XH, Dong Q, Tan L, Yu JT
Hypertension 2020 Jul;76(1):217-225. Epub 2020 May 26 doi: 10.1161/HYPERTENSIONAHA.120.14993. PMID: 32450739
Mol A, Bui Hoang PTS, Sharmin S, Reijnierse EM, van Wezel RJA, Meskers CGM, Maier AB
J Am Med Dir Assoc 2019 May;20(5):589-597.e5. Epub 2018 Dec 21 doi: 10.1016/j.jamda.2018.11.003. PMID: 30583909

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