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Hematology > Heme Synthesis and Disorders
Porphyria, Chester
Article Last Updated: Nov 12, 2008
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Koyamangalath Krishnan, MD, FRCP, FACP, Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, Program Director, Hematology-Oncology Fellowship, James H Quillen College of Medicine at East Tennessee State University
Koyamangalath Krishnan is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians
Coauthor(s):
Stephen J Smith, MD, Assistant Professor of Medicine, Department of Internal Medicine, Division of Hematology/Oncology, East Tennessee State University, James H. Quillen College of Medicine;
Harsha G Vardhana, MD, Chief Fellow, Medical Oncology, Department of Internal Medicine, James H Quillen College of Medicine at East Tennessee State University
Editors: Clarence Sarkodee-Adoo, MD, Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Marcel E Conrad, MD, BS, (Retired) Distinguished Professor of Medicine, University of South Alabama; Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems; Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Author and Editor Disclosure
Synonyms and related keywords:
porphyria, Chester; porphyria, acute porphyria, acute intermittent porphyria, Chester porphyria, Dobson's complaint, heme biosynthesis, enzyme defects, AIP, intermittent acute porphyria, IAP, biochemical defects, variegate porphyria, VP, neurovisceral dysfunction, metabolism error, hypertension, abdominal colic, psychosis, neuropathy, Chester porphyria gene, inborn error of metabolism, porphobilinogen deaminase, protoporphyrinogen oxidase
Background
Porphyrias are inborn errors of metabolism in which specific enzyme defects exist in the heme synthesis pathway. Chester porphyria is a unique type of porphyria, with the clinical picture of acute intermittent porphyria (AIP) and the biochemical defects of both acute intermittent porphyria and variegate porphyria (VP).1
The first description of Chester porphyria is from a clinical observation made by an anesthetist, Zorka Bekerus, in Chester, England, in 1963 (hence the name Chester porphyria). The index case, Peter Dobson, was a salmon fisherman born in 1867 in Chester.2, 3 Numerous family members had the condition, and the family coined the term Dobson's complaint to describe the mysterious illness.4, 5
Related eMedicine topics:
Erythropoietic Porphyria
Erythropoietic Protoporphyria
Porphyria, Acute [in the Pediatrics: General Medicine section]
Porphyria, Hereditary Coproporphyria
Related Medscape topics:
Resource Center Genomic Medicine
Specialty Site Diabetes & Endocrinology
Specialty Site Hematology-Oncology
CME The Diagnosis and Management of Acute Porphyrias
CME A Patient With Unexplained Abdominal Pain
Pathophysiology
Chester porphyria does not conform to any of the recognized types of acute porphyria (see Image 1). The urine porphyrin excretory pattern varies from the pattern of acute intermittent porphyria to variegate porphyria. Chester porphyria exhibits reduction in enzymatic activity of both porphobilinogen deaminase (an enzyme with reduced activity in acute intermittent porphyria) and protoporphyrinogen oxidase (an enzyme with reduced activity in variegate porphyria). Chester porphyria manifests with attacks of neurovisceral dysfunction common to all acute porphyrias. Unlike in variegate porphyrias, cutaneous photosensitivity is not a feature of Chester porphyria.
Frequency
International
The frequency of Chester porphyria is low, and it is only described in the city of Chester, England.
Mortality/Morbidity
- The mortality rate of Chester porphyria is high. In addition, tracing the ancestry of the Chester family, 14 members had peripheral motor neuropathy; 6 of the 14 members developed bulbar palsy, and 4 died as a result.2, 3
- Morbidity is significant. Many members of the Chester family were afflicted with hypertension and renal disease. Significant morbidity is associated with painful porphyric crises in patients affected with Chester porphyria.
Sex
No sex predilection exists in Chester porphyria.
History
Patients with Chester porphyria may present with the following history: - Abdominal pain
- Constipation and vomiting
- Headache
- Seizures
- Paralysis
- Psychologic disturbance
- Palpitations
- High blood pressure
Physical
Patients with Chester porphyria may present with the following physical findings:
- Elevated blood pressure, consistent with hypertension
- Motor neuropathy, as suggested by flaccid paralysis
- Evidence of psychosis6
- Tachyarrhythmias
- Epilepsy
- Renal failure
- Skin manifestations – Not observed
Related Medscape topics:
Specialty Site Cardiology
Specialty Site Neurology & Neurosurgery
Specialty Site Psychiatry & Mental Health
Causes
- Genetic studies have linked the Chester porphyria gene to chromosome arm 11q.7
- Some of the precipitating factors of Chester porphyria include the following drugs:
- Barbiturates
- Aluminum hydroxide
- Tricyclic antidepressants
- Alcohol
- Other precipitating factors are as follows:
- Smoking
- Surgery
- Metabolic abnormalities such as hyponatremia (also listed as a complication)
ALA Dehydratase Deficiency Porphyria
Diabetic Ketoacidosis
Polyarteritis Nodosa
Porphyria, Acute Intermittent
Porphyria, Hereditary Coproporphyria
Toxicity, Arsenic
Toxicity, Lead
Uremia
Other Problems to be Considered
Diabetic ketoacidosis (with abdominal pain)
Poliomyelitis
Polyneuropathies
Tabes dorsalis (with abdominal pain)
Uremia (with abdominal pain)
Vasculitides (polyarteritis nodosa, lead or arsenic poisoning, myopathies, hysteria)
Other porphyrias
Lab Studies
Laboratory workup for Chester porphyria includes the following:
- Urine studies for porphyrins are recommended when an acute attack of porphyria is suspected clinically.8
- Genetic studies can be performed in suspected cases.
Medical Care
- Currently, no cure exists for Chester porphyria. The goal of management is to avoid precipitating factors in cases of suspected porphyrias.
- Treatment is symptomatic.
- Genetic counseling and understanding the disease and its manifestations may be helpful for family members.
Surgical Care
Patients with Chester porphyria are at risk of an acute attack of porphyria at the time of surgery. This is because of stress, metabolic abnormalities, and certain drugs used during surgery.
Currently, no cure exists for Chester porphyria. The goal of management is to avoid precipitating factors in cases of suspected porphyrias. Medically manage symptoms.
Complications
Complications of Chester porphyria include the following: - Malignant hypertension
- Renal failure
- Intracerebral hemorrhage
- Bulbar palsy
- Retinal hemorrhage
- Hyponatremia (also listed as a precipitating factor)
- Peripheral neuropathy
- Myopathy
- Coma and death
Patient Education
- Genetic counseling and discussion about Chester porphyria are essential components of clinical management.
Medical/Legal Pitfalls
- Failure to diagnose Chester porphyria and other porphyrias is a medicolegal pitfall.
Related Medscape topics:
Resource Center Medical Malpractice and Legal Issues
Specialty Site Hematology-Oncology
| Media file 1:
This schematic diagram of biochemical abnormality shows the sites of enzymatic defects of the various porphyrias on the left side of the diagram and the dual enzyme abnormality of Chester porphyria (deficiency of porphobilinogen deaminase [PBGD] and protoporphyrinogen oxidase) on the right. ALA = delta-aminolevulinate; COPRO = copro-porphyrin; HMB = hydroxymethylbilane; HMB-S = hydroxymethylbilane synthase; PROTO = protoporphyrin; URO = uroporphyrin. |
 |  View Full Size Image | |
Media type: Diagram
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- Poblete-Gutiérrez P, Wiederholt T, Martinez-Mir A, et al. Demystification of Chester porphyria: a nonsense mutation in the porphobilinogen deaminase gene. Physiol Res. 2006;55 suppl 2:S137-44. [Medline]. [Full Text].
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- Youngs GR, ed. Dobson's Complaint: The Story of the Chester Porphyria. London, England: The Royal College of Physicians of London; 1998.
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- Norton B, Lanyon WG, Moore MR, et al. Evidence for involvement of a second genetic locus on chromosome 11q in porphyrin metabolism. Hum Genet. Jul 1993;91(6):576-8. [Medline].
- Pischik E, Kazakov V, Kauppinen R. Is screening for urinary porphobilinogen useful among patients with acute polyneuropathy or encephalopathy?. J Neurol. Jul 2008;255(7):974-9. [Medline].
- Billoo AG, Lone SW. A family with acute intermittent porphyria. J Coll Physicians Surg Pak. May 2008;18(5):316-8. [Medline].
- Church SE. The Chester porphyria. MD thesis, University of Liverpool, United Kingdom. 1986.
- Sardh E, Rejkjaer L, Andersson DE, Harper P. Safety, pharmacokinetics and pharmacodynamics of recombinant human porphobilinogen deaminase in healthy subjects and asymptomatic carriers of the acute intermittent porphyria gene who have increased porphyrin precursor excretion. Clin Pharmacokinet. 2007;46(4):335-49. [Medline].
Porphyria, Chester excerpt Article Last Updated: Nov 12, 2008
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