eMedicine Specialties > Dermatology > Pediatric Diseases

Refsum Disease: Treatment & Medication

Author: Anna Zalewska, MD, PhD, Assistant Professor, Adjunct Professor, Department of Dermatology and Venereology, Medical University of Lodz, Poland
Coauthor(s): Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Contributor Information and Disclosures

Updated: Jul 10, 2009

Treatment

Medical Care

Three forms of medical care are used for Refsum disease (RD).

  • Diet (see Diet)
  • Plasmapheresis
    • The main indication for plasmapheresis in patients with Refsum disease is a severe or rapidly worsening clinical condition.17
    • A minor indication is failure of dietary management to reduce a high plasma phytanic acid level.
    • Cascade filtration may be an alternative for plasmapheresis. It is as efficient as plasmapheresis and eliminates the need for albumin replacement.18
  • Local dermatologic drugs to soften the skin (see Medication)

Pharmacological upregulation of the omega-oxidation of phytanic acid may form the basis of the new treatment strategy for adult Refsum disease in the near future.19

A clinical trial that may be of interest is Study of Bile Acids in Patients With Peroxisomal Disorders.

Surgical Care

Bilateral cochlear implantation should be considered for patients with severe dual sensory loss.20  

Consultations

Because of the variety of different symptoms, these patients require consultation from different specialists.

  • Neurologist to estimate neurologic defects
  • Ophthalmologist to exclude ophthalmic impairments
  • Generalist (internal medicine specialist) to exclude abnormalities in the internal organs (especially cardiac ones)
  • Dermatologist to assess skin changes

Diet

Diet is 1 of 3 types of regimens used to treat patients with Refsum disease.
  • Eliminate all sources of chlorophyll from the diet.
    • The major dietary exclusions are green vegetables (source of phytanic acid) and animal fat (phytol).
    • The aim of such dietary treatment is to reduce daily intake of phytanic acid from the usual level of 50 mg/d to less than 5 mg/d.
    • This change is accompanied by increased nerve conduction velocities, return of reflexes, and improvement in sensation and objective coordination.
  • Ichthyosis clears, and its recurrence may be a marker of rising phytanic acid level in blood.
  • Improvement in clinical status as a result of diet is due to the presence of alternative pathway oxidation omega-oxidation that is able to metabolize small amounts of phytanic acid.
  • Lifelong strict adherence to the diet is mandatory. A high carbohydrate intake should be provided to avoid a rapid weight loss as it metabolizes tissue phytanic acid.

Medication

Appropriate medications consist of skin care products (eg, keratolytics, emollients). Recent research has shown that enzymes responsible for the omega-hydroxylation of phytanic acid could be useful in Refsum disease treatment. Elevation of CYP4 enzymes could have a favorable role in the elimination of phytanic acid in persons with Refsum disease.

Keratolytics

Used to soften and exfoliate the skin.


Urea (Carmol, Ureacin-40, Aquacare)

Indicated for hyperkeratosis. Promotes hydration and removal of excess keratin in conditions of hyperkeratosis. Available in 10-40% concentrations.

Adult

Apply to affected area prn

Pediatric

Administer as in adults

May decrease effects of lithium

Documented hypersensitivity; severely impaired renal function; active intracranial bleeding; marked dehydration; frank liver failure; infusion into veins of lower extremities in elderly patients may cause phlebitis and thrombosis

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use near eyes; caution if applied to broken or swollen skin


Ammonium lactate (Lac Hydrin)

Contains lactic acid, an alpha hydroxy acid that has keratolytic action, thus facilitating release of comedones. Comes in 12% and 5% strength. The 12% strength may cause irritation on the face. Causes disadhesion of corneocytes.

Adult

Apply to affected areas prn

Pediatric

Administer as in adults

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Avoid use near eyes, mucosal surfaces, and irritated skin or open lesions; may sting or cause pain if applied on broken skin; may cause irritation with erythema, burning, and peeling if applied to face in 12% concentrations


Mineral oil (Kondremul, Zymenol)

Provides relief of minor skin irritations, and promotes the removal of excess keratin in conditions of hyperkeratosis. Found in a variety of topical lotions.

Adult

Apply to affected area prn

Pediatric

Administer as in adults

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Observe for hypersensitivity reactions

More on Refsum Disease

Overview: Refsum Disease
Differential Diagnoses & Workup: Refsum Disease
Treatment & Medication: Refsum Disease
Follow-up: Refsum Disease
References
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References

  1. Jansen GA, Ferdinandusse S, Hogenhout EM, Verhoeven NM, Jakobs C, Wanders RJ. Phytanoyl-CoA hydroxylase deficiency. Enzymological and molecular basis of classical Refsum disease. Adv Exp Med Biol. 1999;466:371-6. [Medline].

  2. Jansen GA, Ofman R, Ferdinandusse S, et al. Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene. Nat Genet. Oct 1997;17(2):190-3. [Medline].

  3. Singh I, Pahan K, Singh AK, Barbosa E. Refsum disease: a defect in the alpha-oxidation of phytanic acid in peroxisomes. J Lipid Res. Oct 1993;34(10):1755-64. [Medline].

  4. Komen JC, Distelmaier F, Koopman WJ, Wanders RJ, Smeitink J, Willems PH. Phytanic acid impairs mitochondrial respiration through protonophoric action. Cell Mol Life Sci. Dec 2007;64(24):3271-81. [Medline].

  5. Foulon V, Asselberghs S, Geens W, Mannaerts GP, Casteels M, Van Veldhoven PP. Further studies on the substrate spectrum of phytanoyl-CoA hydroxylase: implications for Refsum disease?. J Lipid Res. Dec 2003;44(12):2349-55. [Medline].

  6. Horn MA, van den Brink DM, Wanders RJ, et al. Phenotype of adult Refsum disease due to a defect in peroxin 7. Neurology. Feb 27 2007;68(9):698-700. [Medline].

  7. Jansen GA, Waterham HR, Wanders RJ. Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7). Hum Mutat. Mar 2004;23(3):209-18. [Medline].

  8. Fiskerstrand T, Knappskog P, Majewski J, Wanders RJ, Boman H, Bindoff LA. A novel Refsum-like disorder that maps to chromosome 20. Neurology. Jan 6 2009;72(1):20-7. [Medline].

  9. Bader PI, Dougherty S, Cangany N, Raymond G, Jackson CE. Infantile refsum disease in four Amish sibs. Am J Med Genet. Jan 17 2000;90(2):110-4. [Medline].

  10. Choksi V, Hoeffner E, Karaarslan E, Yalcinkaya C, Cakirer S. Infantile refsum disease: case report. AJNR Am J Neuroradiol. Nov-Dec 2003;24(10):2082-4. [Medline].

  11. Koh JT, Jeong BC, Kim JH, et al. Changes underlying arrhythmia in the transgenic heart overexpressing Refsum disease gene-associated protein. Biochem Biophys Res Commun. Jan 2 2004;313(1):156-62. [Medline].

  12. Leys D, Petit H, Bonte-Adnet C, et al. Refsum's disease revealed by cardiac disorders. Lancet. Mar 18 1989;1(8638):621. [Medline].

  13. Verny C, Prundean A, Nicolas G, et al. Refsum's disease may mimic familial Guillain Barre syndrome. Neuromuscul Disord. Nov 2006;16(11):805-8. [Medline].

  14. Cakirer S, Savas MR. Infantile Refsum disease: serial evaluation with MRI. Pediatr Radiol. Feb 2005;35(2):212-5. [Medline].

  15. Gibberd FB, Feher MD, Sidey MC, Wierzbicki AS. Smell testing: an additional tool for identification of adult Refsum's disease. J Neurol Neurosurg Psychiatry. Sep 2004;75(9):1334-6. [Medline].

  16. Duranti G, Boenzi S, Rizzo C, et al. Urine acylcarnitine analysis by ESI-MS/MS: a new tool for the diagnosis of peroxisomal biogenesis disorders. Clin Chim Acta. Dec 2008;398(1-2):86-9. [Medline].

  17. Harari D, Gibberd FB, Dick JP, Sidey MC. Plasma exchange in the treatment of Refsum's disease (heredopathia atactica polyneuritiformis). J Neurol Neurosurg Psychiatry. Jul 1991;54(7):614-7. [Medline].

  18. Gutsche HU, Siegmund JB, Hoppmann I. Lipapheresis: an immunoglobulin-sparing treatment for Refsum's disease. Acta Neurol Scand. Sep 1996;94(3):190-3. [Medline].

  19. Xu F, Ng VY, Kroetz DL, de Montellano PR. CYP4 isoform specificity in the omega-hydroxylation of phytanic acid, a potential route to elimination of the causative agent of Refsum's disease. J Pharmacol Exp Ther. Aug 2006;318(2):835-9. [Medline].

  20. Raine CH, Kurukulasuriya MF, Bajaj Y, Strachan DR. Cochlear implantation in Refsum's disease. Cochlear Implants Int. Jun 2008;9(2):97-102. [Medline].

  21. Davies MG, Marks R, Dykes PJ, Reynolds D. Epidermal abnormalities in Refsum's disease. Br J Dermatol. Oct 1977;97(4):401-6. [Medline].

  22. Dykes PJ, Marks R, Davies MG, Reynolds DJ. Epidermal metabolism in heredopathia atactica polyneuritiformis (Refsum's disease). J Invest Dermatol. Mar 1978;70(3):126-9. [Medline].

  23. Griffiths WAD, Judge MR. Refsum's disease. In: Champion RH, Burton JL, Burns, eds. Rook/Wilkinson/Ebling Textbook of Dermatology. Oxford: Blackwell Science; 1998:1516-17.

  24. Jansen GA, Hogenhout EM, Ferdinandusse S, et al. Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum's disease. Hum Mol Genet. May 1 2000;9(8):1195-200. [Medline].

  25. Kahlert S, Schonfeld P, Reiser G. The Refsum disease marker phytanic acid, a branched chain fatty acid, affects Ca2+ homeostasis and mitochondria, and reduces cell viability in rat hippocampal astrocytes. Neurobiol Dis. Feb 2005;18(1):110-8. [Medline].

  26. van den Brink DM, van Miert JN, Dacremont G, Rontani JF, Wanders RJ. Characterization of the final step in the conversion of phytol into phytanic acid. J Biol Chem. Jul 22 2005;280(29):26838-44. [Medline].

  27. Weinstein R. Phytanic acid storage disease (Refsum's disease): clinical characteristics, pathophysiology and the role of therapeutic apheresis in its management. J Clin Apher. 1999;14(4):181-4. [Medline].

  28. Wierzbicki AS, Mitchell J, Lambert-Hammill M, et al. Identification of genetic heterogeneity in Refsum's disease. Eur J Hum Genet. Aug 2000;8(8):649-51. [Medline].

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Further Reading

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Keywords

Refsum disease, heredopathia atactica polyneuritiformis, RD, neurocutaneous syndromes, peripheral polyneuropathy, cerebellar ataxia, retinitis pigmentosa, ichthyosis

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Contributor Information and Disclosures

Author

Anna Zalewska, MD, PhD, Assistant Professor, Adjunct Professor, Department of Dermatology and Venereology, Medical University of Lodz, Poland
Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Jacek C Szepietowski, MD, PhD, Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland
Disclosure: Stiefel Salary Employment; Orfagen Consulting fee Consulting; Maruho Consulting fee Consulting; Astellas Consulting fee Consulting

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey P Callen, MD, Professor of Medicine, Chief, Division of Dermatology, University of Louisville School of Medicine
Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and American College of Rheumatology
Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Electrical Optical Sciences Honoraria Consulting; Centocor Honoraria Consulting; Genetech Honoraria Consulting; Celgene Honoraria Consulting

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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