Interpretive Handbook

Test 61261 :
PPOX Gene, Full Gene Analysis

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Variegate porphyria (VP) is an autosomal dominant (AD) cutaneous porphyria that can present with/or without acute attacks that phenocopy acute intermittent porphyria (AIP). The most common clinical presentation of VP is increased photosensitivity, blistering, hyperpigmentation, and skin fragility in sun-exposed areas. The acute attacks of VP can include abdominal pain, 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. Cutaneous manifestations include edema, sun-induced erythema, acute painful photodermatitis, and urticaria. In some cases patients present with isolated photosensitivity.


Variegate porphyria is caused by mutations in the PPOX gene. Mutations are typically inherited in an autosomal dominant fashion with incomplete penetrance, although homozygous mutations have been reported in association with a more severe clinical phenotype in early childhood.


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 variegate porphyria from AIP and hereditary coproporhpyria.


Useful For Suggests clinical disorders or settings where the test may be helpful

Confirmation of variegate porphyria for patients with clinical and biochemical features of the disease


Identification of familial PPOX mutation to allow for genetic testing in family members


Interpretation Provides information to assist in interpretation of the test results

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

A small percentage of individuals who are carriers or have a diagnosis of variegate porphyria may have a mutation that is not identified by this method (eg, large genomic deletions, promoter mutations). The absence of a mutation, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of variegate porphyria. For carrier testing, it is important to first document the presence of a PPOX gene mutation in an affected family member.


In some cases, DNA alterations of undetermined significance may be identified.


Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.


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.  


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.


Mutations in other genes, such as CPOX and HMBS have been shown to cause other forms of porphyrias. Abnormalities in these genes are not detected by this assay.

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, Frank J: 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