Interpretive Handbook

The porphyrias are a group of inborn errors of metabolism resulting from defects in the heme biosynthetic pathway. Enzymatic deficiencies result in the accumulation and excretion of intermediary metabolites in different specimen types. The pattern of excretion of the heme precursors in urine and feces and the accumulation within erythrocytes allow for the detection and differentiation of the hereditary porphyrias. These accumulations cause characteristic clinical manifestations, which may include neurologic and psychological symptoms and cutaneous photosensitivity, depending upon the specific disorder. Although genetic in nature, environmental factors may exacerbate symptoms, significantly impacting the severity and course of disease. Early diagnosis coupled with education and counseling of the patient regarding the disease and treatment including avoidance of precipitating factors are important for successful management.

Historically, the porphyrias have been divided into 2 groups, erythropoietic and hepatic based on the major site of substrate accumulation and/or overproduction. Another classification is based on clinical presentation and divides the porphyrias into acute or nonacute (cutaneous) categories. The acute porphyrias include acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP). The nonacute porphyrias include congenital erythropoietic porphyria (CEP), porphyria cutanea tarda (PCT), and erythropoietic protoporphyria (EPP).

PCT is the most common form of porphyria. It presents clinically with increased skin fragility and the formation of vesicles and bullae on sun-exposed areas of the skin. PCT can be either sporadic (acquired) or inherited in an autosomal dominant manner. A biochemical diagnosis of PCT is characterized by increased urinary excretion of uroporphyrin and heptacarboxylporphyrin. Lesser amounts of hexacarboxylporphyrin, pentacarboxylporphyrin, and coproporphyrin may also be excreted. Hepatoerythropoietic porphyria (HEP) is observed when an individual inherits PCT from both parents. Patients exhibit a similar porphyrin excretion pattern as PCT, although the clinical presentation is similar to what is seen in CEP.

The clinical features of the acute porphyrias include abdominal pain, sensory neuropathy, and psychosis. Photosensitivity is not associated with acute intermittent porphyria (AIP), but may be present in HCP and VP. The biochemical diagnosis of AIP is based upon an increased urinary excretion of porphobilinogen (PBG) and aminolevulinic acid (ALA). In addition, uroporphyrin is also usually increased. A urine specimen obtained during an acute episode is most informative, as these analytes may be normal or only slightly increased between acute episodes of AIP. With respect to HCP and VP, the excretion pattern observed in urine is indistinguishable from one another with elevations of both coproporphyrin and PBG excretion being observed in urine. Fecal porphyrins analysis is recommended to differentiate VP from HCP.

CEP is a rare disorder typically presenting in childhood with prominent photosensitivity and voiding of dark, wine-colored urine. A few milder adult-onset cases have been documented as well as cases that are secondary to myeloid malignancies. A biochemical diagnosis of CEP is characterized by increased urinary excretion of uroporphyrin and coproporphyrin with the excretion of uroporphyrin usually exceeding that of coproporphyrin and the series I isomers predominating. Lesser amounts of the heptacarboxyl-, hexacarboxyl-, and pentacarboxyl porphyrins may be excreted. The urinary excretion of ALA and PBG is usually within normal limits.

Typically, the work up of patients with a suspected porphyria is most effective when following a stepwise approach. See Porphyria (Acute) Testing Algorithm and Porphyria (Cutaneous) Testing Algorithm in Special Instructions, or contact Mayo Medical Laboratories to discuss testing strategies. Refer to The Challenges of Testing For and Diagnosing Porphyrias, Mayo Medical Laboratories Communique 2002 Nov;27(11) for more information.

Differential diagnosis of porphyrias

Differential diagnosis of photosensitive skin manifestations 

Determining whether skin problems are related to an accumulation of porphyrins (renal failure porphyria, porphyria cutanea tarda, congenital erythropoietic porphyria, and erythropoietic protoporphyria) or some other problem

A mild elevation of total plasma porphyrins is an expression of a primary (eg, active porphyria cutanea tarda, congenital erythropoietic porphyria, erythropoietic protoporphyria, variegate porphyria, or hereditary coproporphyria) or secondary defect in the biosynthesis of heme. However, the specific type of porphyria cannot be determined by total plasma porphyrin analysis alone.

When abnormal results are detected, a detailed interpretation is provided, which may include:

-An overview of the results and of their significance

-Elements of differential diagnosis

-Recommendations for additional biochemical testing (ie, enzyme assays)

-Phone number to reach 1 of the laboratory directors in case the referring physician has additional questions

Plasma porphyrins are extremely sensitive to light and may degrade to normal levels if not handled properly. Send specimen frozen in amber vial (Supply T192) to protect from light.

< or =1.0 mcg/dL