Evidence map›Paper›PMID 31822578›Full record

ArticleNeurology2020

Congenital absence of norepinephrine due to

Cyndya A Shibao, Emily M Garland, Bonnie K Black, Christopher J Mathias, Maria B Grant, Allen W Root, David Robertson, Italo Biaggioni

Open access · bronzeAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
  2. Review
  3. Cecytb-2, a CytochromeBiomolecules · 2025
    Article
  4. Article
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  6. Article
  7. All orthostatic hypotension is neurogenic.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2023
    Article
  8. Baroreflex-sympathoneural without baroreflex-cardiovagal failure in neurogenic orthostatic hypotension.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2023
    Article
  9. Different phenoconversion pathways in pure autonomic failure with versus without Lewy bodies.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2021
    Review
  10. Holiday heart syndrome: do not drink during this holiday! and other updates on recent autonomic research.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2021
    Article
  11. Review
  12. Article
  13. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 3 countries.

Cyndya A ShibaoFrom the Departments of Medicine (C.A.S., E.M.G., B.K.B., D.R., I.B.), Neurology (D.R.), and Pharmacology (D.R.), and the Vanderbilt Autonomic Dysfunction Center (C.A.S., E.M.G., B.K.B., D.R., I.B.), Vanderbilt University Medical Center, Nashville, TN; Autonomic & Neurovascular Medicine Center (C.J.M.), Hospital of St John & St Elizabeth; St Mary's Hospital (C.J.M.), Imperial College Healthcare Trust; Institute of Neurology/University College London (C.J.M.), UK; Department of Ophthalmology and Visual Sciences (M.B.G.), School of Medicine, University of Alabama at Birmingham; and Johns Hopkins All Children's Hospital (A.W.R.), St. Petersburg, FL.
Emily M GarlandFrom the Departments of Medicine (C.A.S., E.M.G., B.K.B., D.R., I.B.), Neurology (D.R.), and Pharmacology (D.R.), and the Vanderbilt Autonomic Dysfunction Center (C.A.S., E.M.G., B.K.B., D.R., I.B.), Vanderbilt University Medical Center, Nashville, TN; Autonomic & Neurovascular Medicine Center (C.J.M.), Hospital of St John & St Elizabeth; St Mary's Hospital (C.J.M.), Imperial College Healthcare Trust; Institute of Neurology/University College London (C.J.M.), UK; Department of Ophthalmology and Visual Sciences (M.B.G.), School of Medicine, University of Alabama at Birmingham; and Johns Hopkins All Children's Hospital (A.W.R.), St. Petersburg, FL.
Bonnie K BlackFrom the Departments of Medicine (C.A.S., E.M.G., B.K.B., D.R., I.B.), Neurology (D.R.), and Pharmacology (D.R.), and the Vanderbilt Autonomic Dysfunction Center (C.A.S., E.M.G., B.K.B., D.R., I.B.), Vanderbilt University Medical Center, Nashville, TN; Autonomic & Neurovascular Medicine Center (C.J.M.), Hospital of St John & St Elizabeth; St Mary's Hospital (C.J.M.), Imperial College Healthcare Trust; Institute of Neurology/University College London (C.J.M.), UK; Department of Ophthalmology and Visual Sciences (M.B.G.), School of Medicine, University of Alabama at Birmingham; and Johns Hopkins All Children's Hospital (A.W.R.), St. Petersburg, FL.
Christopher J MathiasFrom the Departments of Medicine (C.A.S., E.M.G., B.K.B., D.R., I.B.), Neurology (D.R.), and Pharmacology (D.R.), and the Vanderbilt Autonomic Dysfunction Center (C.A.S., E.M.G., B.K.B., D.R., I.B.), Vanderbilt University Medical Center, Nashville, TN; Autonomic & Neurovascular Medicine Center (C.J.M.), Hospital of St John & St Elizabeth; St Mary's Hospital (C.J.M.), Imperial College Healthcare Trust; Institute of Neurology/University College London (C.J.M.), UK; Department of Ophthalmology and Visual Sciences (M.B.G.), School of Medicine, University of Alabama at Birmingham; and Johns Hopkins All Children's Hospital (A.W.R.), St. Petersburg, FL.
Maria B GrantFrom the Departments of Medicine (C.A.S., E.M.G., B.K.B., D.R., I.B.), Neurology (D.R.), and Pharmacology (D.R.), and the Vanderbilt Autonomic Dysfunction Center (C.A.S., E.M.G., B.K.B., D.R., I.B.), Vanderbilt University Medical Center, Nashville, TN; Autonomic & Neurovascular Medicine Center (C.J.M.), Hospital of St John & St Elizabeth; St Mary's Hospital (C.J.M.), Imperial College Healthcare Trust; Institute of Neurology/University College London (C.J.M.), UK; Department of Ophthalmology and Visual Sciences (M.B.G.), School of Medicine, University of Alabama at Birmingham; and Johns Hopkins All Children's Hospital (A.W.R.), St. Petersburg, FL.
Allen W RootFrom the Departments of Medicine (C.A.S., E.M.G., B.K.B., D.R., I.B.), Neurology (D.R.), and Pharmacology (D.R.), and the Vanderbilt Autonomic Dysfunction Center (C.A.S., E.M.G., B.K.B., D.R., I.B.), Vanderbilt University Medical Center, Nashville, TN; Autonomic & Neurovascular Medicine Center (C.J.M.), Hospital of St John & St Elizabeth; St Mary's Hospital (C.J.M.), Imperial College Healthcare Trust; Institute of Neurology/University College London (C.J.M.), UK; Department of Ophthalmology and Visual Sciences (M.B.G.), School of Medicine, University of Alabama at Birmingham; and Johns Hopkins All Children's Hospital (A.W.R.), St. Petersburg, FL.
David RobertsonFrom the Departments of Medicine (C.A.S., E.M.G., B.K.B., D.R., I.B.), Neurology (D.R.), and Pharmacology (D.R.), and the Vanderbilt Autonomic Dysfunction Center (C.A.S., E.M.G., B.K.B., D.R., I.B.), Vanderbilt University Medical Center, Nashville, TN; Autonomic & Neurovascular Medicine Center (C.J.M.), Hospital of St John & St Elizabeth; St Mary's Hospital (C.J.M.), Imperial College Healthcare Trust; Institute of Neurology/University College London (C.J.M.), UK; Department of Ophthalmology and Visual Sciences (M.B.G.), School of Medicine, University of Alabama at Birmingham; and Johns Hopkins All Children's Hospital (A.W.R.), St. Petersburg, FL.
Italo BiaggioniFrom the Departments of Medicine (C.A.S., E.M.G., B.K.B., D.R., I.B.), Neurology (D.R.), and Pharmacology (D.R.), and the Vanderbilt Autonomic Dysfunction Center (C.A.S., E.M.G., B.K.B., D.R., I.B.), Vanderbilt University Medical Center, Nashville, TN; Autonomic & Neurovascular Medicine Center (C.J.M.), Hospital of St John & St Elizabeth; St Mary's Hospital (C.J.M.), Imperial College Healthcare Trust; Institute of Neurology/University College London (C.J.M.), UK; Department of Ophthalmology and Visual Sciences (M.B.G.), School of Medicine, University of Alabama at Birmingham; and Johns Hopkins All Children's Hospital (A.W.R.), St. Petersburg, FL. italo.biaggioni@vanderbilt.edu.
St. Mary’s Hospital · ZAUniversity of Alabama at Birmingham · USHospital of St John & St Elizabeth · GBUniversity College London · GB

Funding

The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Visual Phenotyping CoreP30EY003039 · NEI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LAWRENCE C SINCICH · 1985 to 2026
$16.9M
Training CoreU54NS065736 · NINDS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI KAUFMANN, HORACIO · 2009 to 2018
$11.6M
Sympathetic Mechanisms in the Cardiovascular and Metabolic Alterations of ObesityR01HL149386 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BIAGGIONI, ITALO · 2019 to 2023
$3.0M
NCATS NIH HHS UL1 TR000445NEI NIH HHS P30 EY003039NHLBI NIH HHS R01 HL149386NINDS NIH HHS U54 NS065736
6 · The paper itself

Abstract

objectiveCytochrome b561 (CYB561) generates ascorbic acid, a cofactor in the enzymatic conversion of dopamine to norepinephrine by dopamine β-hydroxylase. We propose that the clinical relevance of this pathway can be revealed by characterizing the autonomic and biochemical characteristics of patients with

methodsWe performed autonomic evaluations in 4 patients with lifelong orthostatic hypotension in whom

resultsPatients had disabling lifelong orthostatic hypotension (OH) and impaired blood pressure response to the Valsalva maneuver (VM), with exaggerated hypotension during phase 2 and lack of overshoot during phase 4. Heart rate ratios for sinus arrhythmia and the VM were normal. Plasma norepinephrine and metabolites were undetectable, and plasma dopamine and metabolites were normal. Droxidopa restored norepinephrine levels and improved OH. Patients 1 and 2 were sisters and homozygous for a nonsense mutation in exon 2, c.131G>A, p.Trp44 (Circ Res 2018). Their brother (patient 3) died at age 16 and his DNA was not available. Patient 4 was compound heterozygous; one allele had a missense mutation in exon 2, c157C>T, p.His.53Tyr, and the other had an exon 2 deletion.

conclusionCYB561 deficiency is characterized by selective sympathetic noradrenergic failure with lifelong, disabling OH but with normal sympathetic cholinergic (sweating) and parasympathetic (heart rate regulation) functions. We report a novel case of CYB561 deficiency due to an exon 2 deletion in one allele and a missense mutation in the other. These patients highlight the critical role CYB561 plays in sympathetic function and cardiovascular regulation.

Indexed as

AdolescentAdultCytochrome b GroupFemaleHumansHypotension, OrthostaticMaleMutationNorepinephrinecytochrome b561Cytochrome b GroupNorepinephrine

Identifiers

PMID31822578
PMCPMC6988982
OpenAlexW2995223524

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.