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Urinalysis

Total Porphyrins

Optimal Result: 23.3 - 132.4 mcg/g creat.

What are Porphyrins?

Porphyrins are natural chemicals in the body that help form many important substances in the body such as hemoglobin, the protein in red blood cells that carries oxygen in the blood. Porphyrins are normally present at low concentrations in blood and other body fluids, such as urine.

Why is this test performed?

Porphyrin tests are used to help diagnose and monitor a group of disorders called porphyrias. Porphyrias are a group of rare disorders. An important part of hemoglobin, called heme, is not made properly. Heme is also found in myoglobin, a protein found in certain muscles. There are seven types of porphyria, and each one is associated with a different enzyme deficiency. Most porphyrias are inherited, the result of a gene mutation. They may be classified according to the signs and symptoms of the disease as neurological, cutaneous, or both.

What are signs and symptoms?

The porphyrias that cause neurological symptoms present with acute attacks lasting days or weeks. Signs and symptoms during the attack include abdominal pain, constipation, confusion, hallucinations, and/or seizures. There are four neurologic porphyrias: acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and the very rare ALA dehydratase deficiency porphyria (ADP). Some cases of VP and HCP may also have skin-related symptoms.

Optimal results:

Optimal results vary depending on the type of porphyrin tested. In general, for a 24-hour urine test of total porphyrins, the range is about 23.3 – 132.4 mcg/g creat.

References: 

  1. Fuller SJ, Wiley JS. Heme biosynthesis and its disorders: porphyrias and sideroblastic anemias. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles and Practice. 6th ed. Philadelphia, PA: Elsevier Saunders; 2013:chap 36.
  2. Habif TP. Light-related diseases and disorders of pigmentation. In: Habif TP, ed. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. 6th ed. Philadelphia, PA: Elsevier; 2016:chap 19.
  3. Hift RJ. The porphyrias. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 210.

What does it mean if your Total Porphyrins result is too high?

Elevated Total Porphyrins: Causes, Conditions, and Implications

Elevated levels of total porphyrins in the body often indicate a disruption in the production of heme, a vital component of hemoglobin responsible for carrying oxygen in the blood. Porphyrins are molecules that play a crucial role in this process. Heme is produced through a multi-step pathway, with porphyrins serving as intermediates. When any stage of this pathway is disrupted, porphyrins can accumulate in the body, potentially leading to a range of symptoms and conditions.

While porphyrins are essential for heme synthesis, their excessive accumulation can be problematic. The specific type and concentration of accumulated porphyrins determine their potential harm. These disruptions are often associated with a group of disorders called porphyrias, which can be genetic or acquired. Each type of porphyria involves a specific enzyme defect in the heme production pathway, leading to the accumulation of different porphyrins and resulting in varied symptoms.

Key Conditions Associated with Elevated Total Porphyrins

1. Porphyrias

Porphyrias are the primary cause of elevated total porphyrins. These rare genetic disorders result from the body's inability to properly produce heme. Porphyrias are typically classified into two main categories:

Acute Porphyrias

These forms primarily affect the nervous system and are characterized by sudden, severe symptoms such as abdominal pain, vomiting, confusion, and even seizures. Examples include:

  • Acute intermittent porphyria (AIP)
  • Hereditary coproporphyria (HCP)
  • Variegate porphyria (VP)

During acute attacks, porphyrins can accumulate in the liver and enter the bloodstream and urine. Early diagnosis is critical as acute porphyrias can be life-threatening without proper treatment.

Cutaneous Porphyrias

These forms primarily affect the skin, leading to photosensitivity, blistering, and skin damage. The most common is porphyria cutanea tarda (PCT), often triggered by factors like alcohol use, liver disease, or iron overload.It's important to note that some porphyrias, like VP and HCP, can present with both acute and cutaneous symptoms.

2. Liver Disorders

The liver plays a crucial role in porphyrin metabolism and elimination. Certain liver diseases, particularly those affecting heme synthesis or porphyrin metabolism, can lead to increased porphyrin levels. These may include hepatitis, cirrhosis, or hepatocellular carcinoma. Elevated total porphyrins in individuals with liver disease may serve as an early marker of liver dysfunction, guiding further investigation and treatment.

3. Heavy Metal Exposure

Exposure to certain heavy metals can interfere with the enzymes in the heme production pathway, causing porphyrin accumulation. Lead is a primary culprit, inhibiting specific enzymes like ALA dehydratase. However, other heavy metals such as mercury and arsenic can also disrupt heme biosynthesis and potentially affect porphyrin levels. Symptoms of heavy metal poisoning can include abdominal pain, neurological issues, and anemia.

4. Iron Overload Disorders

Conditions like hereditary hemochromatosis can cause elevated porphyrin levels. Excess iron in the body can affect liver function and interfere with porphyrin metabolism. Patients might present with liver disease, fatigue, joint pain, and skin pigmentation issues.

5. Alcoholism

Chronic alcohol consumption can elevate total porphyrins, particularly in those susceptible to porphyria cutanea tarda. Alcohol can disrupt liver function and induce enzymes that exacerbate porphyrin buildup.

6. Certain Medications

Some drugs can trigger or exacerbate porphyria symptoms by interfering with the heme synthesis pathway. Examples include barbiturates, sulfonamides, and some anticonvulsants.

7. Photosensitivity

People with elevated total porphyrins, especially in cutaneous porphyrias, often develop photosensitivity. This abnormal skin reaction to sunlight can cause burning, blistering, and swelling.

Diagnosis and Testing

Elevated total porphyrins can be detected through blood, urine, or stool tests. However, it's crucial to emphasize that the pattern of porphyrin elevation (which specific porphyrins are elevated) is key for diagnosing the type of porphyria or other underlying condition. A comprehensive porphyrin profile, rather than just total porphyrins, is typically used for accurate diagnosis.

  • Urine Test: Can show elevated levels of total porphyrins, particularly during an acute porphyria attack.
  • Blood Test: Elevated porphyrins in the blood may indicate liver dysfunction or ongoing heme synthesis problems.
  • Stool Test: Can reveal elevated porphyrins, helping to identify specific types of porphyria.

Treatment and Management

The treatment of elevated porphyrin levels depends on the underlying cause:

- For acute porphyrias, treatment often involves managing symptoms during an attack. Intravenous glucose is typically the first-line treatment, with hemin reserved for severe cases or those not responding to glucose.

- In porphyria cutanea tarda, avoiding sunlight and certain triggers like alcohol is crucial. Treatments may include phlebotomy to reduce iron levels and medications like hydroxychloroquine.

- Addressing underlying conditions like liver disease, heavy metal exposure, or iron overload can help normalize porphyrin levels.

In conclusion, elevated total porphyrins often signal conditions involving the heme biosynthesis pathway. Whether due to porphyrias, liver dysfunction, or environmental factors, high porphyrin levels are a key diagnostic clue. They should prompt further medical evaluation to determine the root cause and guide appropriate treatment strategies.

What does it mean if your Total Porphyrins result is too low?

Abnormal results may be due to:

-Liver cancer
-Hepatitis
-Lead poisoning
-Porphyria (several types)

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