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HomeEndocrinologyDiseases of Tetrapyrrole Metabolism - Refsum Disease and the Hepatic Porphyrias

Diseases of Tetrapyrrole Metabolism – Refsum Disease and the Hepatic Porphyrias

Practice Essentials

Refsum disease and the hepatic porphyrias are rare inherited neurodegenerative conditions with exacerbations and remissions due to abnormal metabolism of large tetrapyrrole molecules. Two common examples of large tetrapyrrole molecules are chlorophyll a, the photosynthetic pigment of green plants, and heme, the prosthetic group of hemoglobin (see the image below). Side groups on both species involve relatively small organic groups (methyl, vinyl, and free propionyl); one major exception is phytol, a large hydrocarbon alcoholic substituent on chlorophyll. Patients in both disease categories must avoid foods and drugs that lead to high levels of the relevant biological toxin, which can trigger or perpetuate an exacerbation.

Tetrapyrrole molecules are large-ringed structures

Tetrapyrrole molecules are large-ringed structures developed from 4 pyrrole groups and used in energy metabolism in both plants and animals.

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In acute disease, blood or urine tests are definitive, including increased phytanic acid in serum for Refsum disease; increased ALA and porphobilinogen (PBG) in the urine and serum  for porphyrias; and low uroporphyrinogen decarboxylase
 level in porphyria cutanea tarda. When porphyria is suspected in a patient without a family history, lead levels from blood or 24-hour urine collection should be obtained to exclude lead poisoning. 

No specific treatments are indicated in Refsum disease, other than dietary restrictions of beef and milk products. Avoiding direct sunlight is necessary in preventing photosensitive dermatitis, especially in PCT.

Schedule annual or 6-month visits for a general physical examination. Analyze the patient’s progress in avoiding exacerbating triggers and order blood tests used to monitor adequate control (phytanic acid or ALA/PBG).

Gabapentin: This agent is useful as a long-term anticonvulsant in patients with hepatic porphyrias. It is the first drug of choice because it does not require hepatic metabolism; incidentally, it also is well tolerated by these patients in treatment of chronic pain, as an alternative to narcotics, which invoke liver metabolism.

Levetiracetam: This agent is a viable alternative to gabapentin if the side effect profile (most notably somnolence) makes gabapentin undesirable. It does not provide a pain-reducing action like gabapentin.

Triple bromide is an alternative to the more traditional anticonvulsant choices of gabapentin and levetiracetam for long-term anticonvulsant therapy. Before the discovery of safe traditional anticonvulsants, it was the only treatment option for seizures in patients with hepatic porphyria. No specific dosing requirement is known, but the therapeutic range is 60-90 mg/dL to avoid toxic encephalopathy. Bromide preparation requires the assistance of a skilled pharmacist with compounding experience.

Because of its renal clearance, diphenhydramine is safe for use as a sleeping aid or antianxiety medication.

Although a gastroenterologist or a physician with specific interest in porphyria may be helpful in planning disease management, a doctoral level clinical pharmacist or pharmacologist is especially helpful in making choices of safe drug combinations. Medical geneticists can help establish diagnostic histories and help to order the appropriate diagnostic tests as well as provide genetic counseling.

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