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Biochemical testing strategies for the porphyrias

Case 1: A 25-year-old female patient presents in the emergency room with severe abdominal pain, tachycardia and hypertension. Her medical record reveals that she has presented with the same symptoms several times over the last few years. Abdominal imaging and routine blood work have been normal. 

Case 2: A 60-year-old man presents with history of skin fragility and blistering. This is visible on the backs of his hands and on his face. He has not experienced acute abdominal attacks.

In both cases, a porphyria is suspected. The porphyrias are a group of 8 metabolic disorders, each caused by impairment of one of the enzymes in the heme biosynthetic pathway. Types of porphyrias can be grouped by clinical presentation: neurovisceral (acute hepatic), cutaneous (skin), or dual (with neurovisceral and/or cutaneous symptoms possible). Timely and accurate diagnosis is important for determining appropriate management. Biochemical testing on urine, blood, and/or fecal specimens is used to identify and differentiate porphyrias based on patterns unique to each porphyria type. However, diagnosing porphyrias is challenging owing to the rarity of these disorders, variable and sometimes nonspecific symptoms, and the possibility of normal biochemistry between episodes. Here, we review 4 steps to make testing for the porphyrias more successful.

  1. Clarify the symptoms. In case 1, the provider determined that the patient had neurovisceral symptoms, including acute abdominal pain. In case 2, the provider clarified that the symptoms were cutaneous, including skin fragility and bullae (blisters). He had not experienced an acute neurovisceral attack.
  2. Plan your first line of tests. In case 1, the provider was chiefly suspicious of a neurovisceral porphyria, so she ordered urine PBG (porphobilinogen), urine ALA (delta-aminolevulinic acid), and Fractionated Porphyrins. In case 2, the provider was primarily suspicious of a cutaneous porphyria, blistering type. So, Fractionated Porphyrins were planned.
  3. Wait for symptoms to be active. Because the first patient experienced intermittent acute attacks, the provider ordered the testing and specimen collection during the attack. If the patient was in remission, specimen collection should wait until the next attack. In case 2, because the patient had not experienced acute attacks, and the cutaneous symptoms were chronic, the provider ordered the testing and scheduled collection right away.
  4. Follow the pattern. In case 1, the ALA and PBG were elevated, as well as the Fractionated Porphyrins, primarily uroporphyrins I and III. This was interpreted as consistent with Acute Intermittent Porphyria (AIP). In case 2, Fractionated Porphyrins revealed elevations mostly of uroporphyrins III, as well as some elevations of hepta-, hexa-, and penta-carboxyl porphyrin. This was interpreted as consistent with Porphyria Cutanea Tarda (PCT). Following diagnosis, treatment can be initiated to manage symptoms

To assist providers in testing strategy, Quest offers a Test Guide for the Porphyrias. This is available in our online test directory: We invite you to explore the background information, or just skip to quick symptom-based algorithms, as a resource for successful testing when considering the porphyrias for your patient. To talk to a genetic counselor to learn more about porphyrias, please contact Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463).

This information is not intended to substitute for the treating health care provider’s assessment of their patient’s medical status that should be based on the health care provider’s education, experience and clinical assessment of their patient.