Diseases of Tetrapyrrole Metabolism - Refsum Disease and the Hepatic Porphyrias Follow-up

  • Author: Norman C Reynolds Jr, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA   more...
 
Updated: Feb 3, 2012
 

Further Outpatient Care

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).

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Inpatient & Outpatient Medications

  • 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
    • This is an alternative to the more traditional anticonvulsant choices of gabapentin and levetiracetam for long-term anticonvulsant therapy. Prior to 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.
  • Diphenhydramine: Because of its renal clearance, this drug is safe for use as a sleeping aid or antianxiety medication.
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Deterrence/Prevention

Both Refsum disease and the hepatic porphyrias have diet and drug restriction requirements, which are key elements in medical management (see Treatment).

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Prognosis

  • Prognosis in Refsum disease and the hepatic porphyrias depends entirely on the proper dietary and drug restrictions (see Treatment).
  • The patient's ability to survive an acute exacerbation depends upon the adequacy of acute care (especially the care available in an intensive care unit).
  • Survival in an acute porphyric attack depends on monitoring levels of porphyrins and the proper use of D10W and hemin infusions (see Treatment). Despite appropriate treatment measures, mortality rate in acute attacks of acute intermittent porphyria may be as high as 25%.
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Patient Education

  • Both patients with Refsum disease and those with porphyria must become experts in understanding their disease. Both the Hereditary Disease Foundation and the American Porphyria Foundation can be a source of peer support and information for patients and physicians.
  • Monitoring of phytanic acid and ALA/PBG levels is a key element in providing outpatient treatment.
  • For patients with Refsum disease, specific review of safe dietary patterns must be a regular part of outpatient care.
  • Safety of specific drugs must be emphasized to the patient with porphyria (ie, avoiding drugs that induce cytochrome P450 activity). Encourage patients to seek advice by telephone if they have questions or concerns.
  • Genetic inheritance patterns must be understood, so that the patient can exercise responsibility in sexual relations or family planning.
    • Patients with porphyria have a 50% risk of passing along an autosomal-dominant trait with high expressivity.
    • Patients with Refsum disease should avoid marriage or sexual involvement with blood relatives (consanguinity), especially if distant relatives have diagnoses of neurodegenerative disease with childhood onset. Planning offspring is especially difficult, since no simple method is available to detect heterozygotes in this autosomal-recessive disease.
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Contributor Information and Disclosures
Author

Norman C Reynolds Jr, MD  Neurologist, Veterans Affairs Medical Center of Milwaukee; Clinical Professor, Medical College of Wisconsin

Norman C Reynolds Jr, MD is a member of the following medical societies: American Academy of Neurology, Association of Military Surgeons of the US, Movement Disorders Society, Sigma Xi, and Society for Neuroscience

Disclosure: Nothing to disclose.

Specialty Editor Board

Ann M Neumeyer, MD  Medical Director, Lurie Family Autism Center/LADDERS; Assistant Professor of Neurology, Harvard Medical School; Child Neurologist, Massachusetts General Hospital

Ann M Neumeyer, MD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, and Massachusetts Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Kenneth J Mack, MD, PhD  Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic

Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience

Disclosure: Nothing to disclose.

Chief Editor

Stephen A Berman, MD, PhD, MBA  Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, and Phi Beta Kappa

Disclosure: Nothing to disclose.

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Tetrapyrrole molecules are large-ringed structures developed from 4 pyrrole groups and used in energy metabolism in both plants and animals.
Three characteristic substrate molecules of the heme porphyrin pathway.
 
 
 
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