Synonym/Acronym
Blood: Erythrocyte protoporphyrin, EP, free erythrocyte protoporphyrin, FEP; and Urine: Coproporphyrin, porphobilinogen, urobilinogen, and other porphyrins.
Rationale
To assist in diagnosing acquired and inherited conditions associated with porphyrias, such as anemias related to chronic disease, hemolysis, iron deficiency, and heavy metal toxicity.
Patient Preparation
There are no food, fluid, activity, or medication restrictions unless by medical direction. Usually, a 24-hr urine collection is ordered for urine testing. As appropriate, provide the required urine collection container and specimen collection instructions.
Normal Findings
Method: Blood: Fluorometry for erythrocyte protoporphyrin; Urine: High-performance liquid chromatography for porphyrins; spectrophotometry for porphobilinogen.
Blood Study—Erythrocyte Protoporphyrin (EP)
| Conventional Units | SI Units (Conventional Units × 0.0178) |
|---|
| Adult | | | Male | | | Less than 30 mcg/dL | Less than 0.534 micromol/L | | Female | | | Less than 40 mcg/dL | Less than 0.712 micromol/L |
|
Urine
| Test | Units |
|---|
| Coproporphyrins | | | Male | 0–230 nmol/24 hr | | Female | 0–170 nmol/24 hr | | Hexacarboxylporphyrin | 0–8 nmol/24 hr | | Heptacarboxylporphyrin | 0–9 nmol/24 hr | | Uroporphyrins | 0–30 nmol/24 hr | | Porphobilinogen | 0–2 mg/24 hr |
|
Study type: Blood collected in a lavender-top [EDTA], green-top [heparin], or plain red-top tube; Urine from a random or timed specimen collected in a clean, amber-colored plastic collection container with sodium carbonate as a preservative; related body system: Circulatory/Hematopoietic system.
The porphyrias are a group of conditions affecting heme synthesis. Porphyria can be acquired or inherited.
Inherited—Each type of inherited porphyria is caused by an enzyme mutation that results in defective heme synthesis. Erythropoietic and hepatic porphyrias are rare. The two main categories of genetically determined porphyrias are- Erythropoietic porphyrias in which major abnormalities occur in red blood cell (RBC) chemistry and
- Hepatic porphyrias in which heme precursors are found in urine and feces.
Acquired—More common than inherited- Lead poisoning is the most common cause of acquired porphyrias; other heavy metals implicated in acquired porphyrias include, for example, arsenic, cadmium, and mercury.
- Acquired porphyrias are characterized by greater accumulation of precursors in urine and feces than in RBCs.
In the absence of normal heme synthesis, an accumulation of porphyrins in blood and increased excretion of porphyrins in urine occur. Protoporphyrin comprises the predominant porphyrin in RBCs, which combines with iron to form the heme portion of hemoglobin. Porphyrins are reddish fluorescent compounds. Depending on the type of porphyrin present, the urine may be reddish, resembling port wine.
The EP test measures the concentration of nonheme protoporphyrin in RBCs and is considered of value in evaluating suspected hereditary erythropoietic porphyria or erythropoietic protoporphyria. Protoporphyrin converts to bilirubin, combines with albumin, and remains unconjugated in the circulation after hemoglobin breakdown. Increased amounts of protoporphyrin can be detected in erythrocytes, urine, and stool in conditions interfering with heme synthesis.
Generally, a step-wise testing algorithm is most useful in the diagnosis of porphyrias. For additional information regarding evaluation of the porphyrias and heavy metal intoxication, refer to the studies titled “Delta-Aminolevulinic Acid” and “Lead.”
| Type of Porphyria | Classification Can Be Based on Site Where the Protoporphyrin Accumulation Originated: Erythropoietic (originating in the bone marrow) or Hepatic (originating in the liver) | Classification Can Also Be Based on Site Where Symptoms First Appear or Time Frame of Appearance of Symptoms: Cutaneous or Acute | Inheritance Pattern | | Acute intermittent porphyria | Hepatic | Acute intermittent episodes are multifactorial rather than driven primarily by enzyme mutations | Autosomal dominant | | Aminolevulinic acid-dehydratase porphyria | Hepatic | Acute | Autosomal recessive | | Erythropoietic protoporphyria | Erythropoietic | Cutaneous | X-linked protoporphyria | | Hepatoerythropoietic porphyria | Hepatic | Cutaneous | Autosomal recessive | | Hereditary coproporphyria | Hepatic | Acute and cutaneous | Autosomal dominant | | Hereditary erythropoietic porphyria | Erythropoietic | Cutaneous | Autosomal recessive | | Porphyria Cutanea tarda (inherited type) | Hepatic | Cutaneous | Autosomal dominant | | Variegate porphyria | Hepatic | Acute and cutaneous | Autosomal dominant |
|
Erythropoietic porphyrias
Erythropoietic porphyrias can result in anemia and splenomegaly. EP is elevated in cases of lead toxicity or chronic lead exposure.
Hepatic porphyrias
Hepatic porphyrias can lead to cirrhosis of the liver and cholelithiasis related to deposition of protoporphyrin.
Cutaneous porphyrias
Cutaneous porphyrias cause photosensitivity; skin damage is worse in the spring and summer.
Acute porphyrias
Signs and symptoms of acute porphyrias appear quickly, are short-lived, and mainly affect the nervous system.
Environmental and lifestyle factors that may instigate occurrence and severity of the disease include- Alcohol use
- Hormones
- Low-calorie diets
- Periods of fasting
- Simultaneous occurrence of multiple conditions
- Specific drugs
- Tobacco use
Factors That May Alter the Results of the Study
- Drugs and other substances that may increase blood EP levels include erythropoietin.
- Drugs and other substances that may increase urine porphyrin levels include acriflavine, ethoxazene, griseofulvin, hexachlorobenzene, oxytetracycline, and sulfonmethane
- Exposure of the specimen to light can falsely decrease values.
- Failure to collect all urine and store specimen properly during the 24-hr test period will interfere with results.
Other Considerations
- Numerous drugs and other substances are suspected as potential initiators of acute attacks, but drugs classified as unsafe for high-risk individuals include antipyrine, barbiturates, N-butylscopolammonium bromide, carbamazepine, carbromal, chlorpropamide, danazol, dapsone, diclofenac, diphenylhydantoin, ergot preparations, ethchlorvynol, ethinamate, glutethimide, griseofulvin, N-isopropyl meprobamate, meprobamate, methyprylon, novobiocin, phenylbutazone, primidone, pyrazolone preparations, succinimides, sulfonamide antibiotics, sulfonethylmethane, sulfonmethane, synthetic estrogens and progestins, tolazamide, tolbutamide, trimethadione, and valproic acid.
Increased In
Blood
- Anemia of chronic disease (related to accumulation of protoporphyrin in the absence of available iron)
- Conditions with marked erythropoiesis (e.g., hemolytic anemias) (related to increased cell destruction)
- Erythropoietic protoporphyria (related to abnormal increased accumulation)
- Heavy metal poisoning (related to a disturbance in the heme biosynthetic pathway where lead interferes with the enzyme, amino levulinic acid dehydrase, that is responsible for a critical step in heme synthesis)
- Hereditary erythropoietic porphyria
- Iron-deficiency anemias (related to accumulation of protoporphyrin in the absence of available iron)
- Porphyria cutanea tarda
- Some sideroblastic anemias
Urine
Accumulation of porphyrins or porphyrin precursors in the body is common to the various types of porphyrias. Excessive amounts of circulating porphyrins and precursors are excreted in the urine.
- Acute intermittent porphyria (related to an autosomal dominant disorder resulting in a deficiency of the enzyme porphobilinogen deaminase and increased excretion of porphobilinogen and delta-aminolevulinic acid [delta-ALA] in the urine)
- Acquired or chemical porphyrias (heavy metal, benzene, or carbon tetrachloride toxicity; drug induced) (related to a disturbance in the heme biosynthetic pathway and increased excretion of delta-aminolevulinic acid in the urine)
- ALAD deficiency porphyria(related to an autosomal recessive disorder resulting in a deficiency of the enzyme delta-aminolevulinic acid dehydratase and increased excretion of delta-ALA in the urine)
- Hepatoerythropoietic porphyria (related to an autosomal recessive disorder resulting in a deficiency of the enzyme uroporphyrinogen decarboxylase and increased excretion of uroporphyrin and heptacarboxylporphyrin in the urine)
- Hereditary coproporphyria (related to an autosomal dominant disorder resulting in a deficiency of the enzyme coproporphyrinogen oxidase and increased excretion of porphobilinogen, delta-ALA, and coproporphyrin in the urine)
- Porphyria cutanea tarda (related to an acquired deficiency of the enzyme uroporphyrinogen decarboxylase activated by exposure to triggers such as iron, alcohol, hepatitis C virus, HIV, or estrogens and increased excretion of uroporphyrin, heptacarboxylporphyrin, and coproporphyrin in the urine)
- Variegate porphyrias(related to an autosomal dominant disorder resulting in a deficiency of the enzyme protoporphyrinogen oxidase and increased excretion of porphobilinogen, coproporphyrin, and delta-ALA in the urine during attacks; excretion of normal levels may be found between attacks)
Decreased In
N/A
Before the Study: Planning and Implementation
Teaching the Patient What to Expect
- Discuss how this test can assist in evaluating for specific types of anemias, heavy metal poisoning, or other conditions producing increased levels of heme precursors called porphyrias.
- Explain that a blood and/or urine sample is needed for the test.
- Information regarding urine specimen collection is presented with other general guidelines in Appendix A: Patient Preparation and Specimen Collection.
- Discuss the genetic component of inheritance associated with diagnosis.
- Discuss reportable symptoms the patient should be aware of that may indicate an active disease process.
- Active disease—gastrointestinal and urinary symptoms include abdominal pain, constipation, diarrhea, nausea, vomiting, and difficulty urinating (urine may be red or brown).
- Active disease—respiratory and symptoms is difficulty breathing.
- Active disease—musculoskeletal symptoms include muscle pain, numbness, tingling, and weakness of the abdomen, chest, back, and leg.
- Active disease—changes in the skin include pigment changes, erythema, and itching fragile skin.
- Additional active disease symptoms include anxiety, confusion, fever, hallucinations, hirsutism, hypertension, edema, seizures, tachycardia, edema, light sensitivity.
Potential Nursing Actions
- Include on the 24-hr urine container’s label the amount of urine, test start and stop times, and ingestion of any foods or medications that can affect test results.
After the Study: Implementation & Evaluation Potential Nursing Actions
Treatment Considerations
- Discuss the implications of abnormal test results on the patient’s lifestyle.
- Provide education related to the clinical implications of the test results.
- Discuss symptoms associated with the specifically diagnosed porphyria.
Nutritional Considerations
- Increased delta-ALA levels may be associated with an acute porphyria attack.
- Patients prone to porphyria attacks should eat a normal or high-carbohydrate diet.
- Dietary recommendations for those with porphyria may be indicated and will vary depending on the condition and its severity; however, wide variations or restrictions in dietary carbohydrate content should be avoided, even for short periods of time.
- Treatment of an acute attack may include IV administration of dextrose (glucose) and heme. Less severe attacks may be treated with oral sources of dextrose (e.g., sugar added to orange juice). Glucose suppresses an enzyme involved in heme production, and the infusion of available heme also decreases the level of heme synthesis/heme precursors in the blood.
- After recovering from a porphyria attack, the patient’s daily intake of carbohydrates should be 300 g or more per day.
- Some canned goods and candies imported from other countries may have been produced using heavy metal-contaminated ingredients (e.g., tamarind products packed in heavy metal-glazed pots, minimally refined chili powder), heavy metal-contaminated ink used to label candy packaging, or by poor manufacturing and storage processes. As appropriate, health-care providers should provide culturally sensitive education and discuss the safety issues related to consuming imported canned foods and candies.
Clinical Judgement
- Consider how to convey the importance of diet modification to decrease risk of porphyria attacks and how to best approach the subject of genetic testing related to the disease process.
Follow-Up and Desired Outcomes
- Acknowledges contact information provided for the American Porphyria Foundation (https://porphyriafoundation.org/).
- Agrees to genetic counseling and screening related to diagnosis.