MAJOR REVIEW Adult Refsum Disease: A Form of Tapetoretinal Dystrophy Accessible to Therapy Klaus Ru ¨ether, MD, 1 Eleanor Baldwin, BSc, RD, 2 Minne Casteels, MD, PhD, 3 Michael D. Feher, MD, FRCP, 2 Morten Horn, MD, 4 Susan Kuranoff, MA, 5 Bart P. Leroy, MD, PhD, 6 Ronald J. Wanders, PhD, 7 and Anthony S. Wierzbicki, DM, Dphil, FRCPath 2 1 Charite ´-Eye Hospital, Campus Virchow-Klinikum, Berlin, Germany; 2 Refsums Clinic Chelsea and Westminster Hospital Foundation Trust, London, UK; 3 Department of Molecular Cell Biology, Katholieke Universiteit Leuven, Belgium; 4 Department of Neurology, Ulleval University Hospital, Oslo, Norway; 5 Refsum Disease Support Network, Basel, Switzerland; 6 Department of Ophthalmology and Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium; and 7 Genetic Metabolic Diseases Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Abstract. Adult Refsum disease is characterized by an elevated plasma phytanic acid level and high concentrations of phytanic acid in a variety of tissues. Besides tapetoretinal degeneration, additional symptoms are anosmia, skeletal malformations, chronic polyneuropathy, cerebellar ataxia, sensori- neural hearing loss, ichthyosis, and cardiac abnormalities. A diet low in phytanic acid ameliorates polyneuropathy and ataxia and slows or even stops the other manifestations. In order to be able to apply dietary therapy, as many patients as possible (even better if all of them are) have to be identified at an early stage. The ophthalmologist plays a crucial role in achieving this goal because of the early manifestation of the tapetoretinal degeneration. (Surv Ophthalmol 55:531--538, 2010. Ó 2010 Elsevier Inc. All rights reserved.) Key words. adult Refsum disease  anosmia  ataxia  blood plasma filtration  ichthyosis  phytanic acid  polyneuropathy  sensorineural hearing loss  tapetoretinal degeneration I. Introduction Adult Refsum disease (ARD, OMIM # 266500), often referred to as Refsum disease, has long been conceived as a complex disorder with involvement of multiple systems, including the retina. The modern view is that adult Refsum disease is first and foremost a retinopathy in which additional symptoms may develop if not treated appropriately. The full clinical picture includes retinitis pigmentosa (RP), hand--feet deformities, anosmia, sensorineural hearing loss, a chronic sensorimotor polyneurop- athy, ataxia, ichthysosis and, in severe cases, cardio- myopathy 34 (Table 1). The disorder was first described in 1946 by Norwegian neurologist Sigvald Refsum (1907-- 1991). 28 British neurologist Brian Gibberd (1931-- 2006) further characterized the manifestations of the disease and established the routine treatment with a diet low in phytanic acid. This was possible after Klenk and Kahlke in 1963 discovered elevated 531 Ó 2010 by Elsevier Inc. All rights reserved. 0039-6257/$ - see front matter doi:10.1016/j.survophthal.2010.03.007 SURVEY OF OPHTHALMOLOGY VOLUME 55  NUMBER 6  NOVEMBER–DECEMBER 2010