CPOX Gene, Known Mutation
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Hereditary coproporphyria (HCP) is an autosomal dominant (AD) acute hepatic porphyria that presents with clinical attacks of neurologic dysfunction, commonly characterized as abdominal pain. However, these acute attacks are variable and can include vomiting, diarrhea, constipation, urinary retention, acute episodes of neuropathic symptoms, psychiatric symptoms, seizures, respiratory paralysis, tachycardia, and hypertension. Respiratory paralysis can progress to coma and death. HCP is also associated with cutaneous manifestations, including edema, sun-induced erythema, acute painful photodermatitis, and urticarial. In some cases, patients present with isolated photosensitivity.
HCP is caused by AD mutations in the CPOX gene. Mutations may have incomplete penetrance. Homozygous mutations in CPOX have been reported in association with a more severe, phenotypically distinct condition called harderoporphyria that is characterized by neonatal hemolytic anemia with mild residual anemia during childhood and adulthood. Affected patients may also present with skin lesions and fecal harderoporphyin accumulation may be observed. This condition is inherited in an autosomal recessive pattern and all patients identified to date have been heterozygous or homozygous for the K404E mutation.
For HCP, acute attacks may be prevented by avoiding both endogenous and exogenous triggers. These triggers include porphyrogenic drugs, hormonal contraceptives, fasting, alcohol, tobacco, and cannabis.
Fecal porphyrins analysis and quantitative urinary porphyrins analysis are helpful in distinguishing HCP from other forms of acute porphyria.
Predictive testing for hereditary coproporphyria or harderoporphyria when mutation in the CPOX gene has been identified in an affected family member
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order CPOXS / CPOX Gene, Full Gene Analysis.
Analysis is performed for the familial mutation provided only. This assay does not rule-out the presence of other mutations within this gene or within other genes that may be associated with porphyria.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false paternity, could lead to erroneous interpretation of results.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Siegesmund M, van Tuyll van Serooskerken AM, Poblete-Gutierrez P, et al: The acute hepatic porphyrias: current status and future challenges. Best Pract Res Clin Gastroenterol 2010 Oct;24(5):593-605
2. Anderson KE, Bloomer JR, Bonkovsky HL, et al: Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med 2005 Mar 15;142(6):439-450
3. Schmitt, C, Gouya L, Malonova E, et al: Mutations in human CPO gene predict clinical expression of either hereditary coproporphyria or erythropoietic harderoporphyria. Hum Mol Genet 2005;14(20):3089-3098