Diagnosis and Metabolic Management of Adult Refsum Disease: Guidance From the Medical and Scientific Committee of Global DARE (Defeat Adult Refsum Everywhere).

Radha Ramachandran, Raphael Buttigieg, Florian Eichler, Bart P Leroy, Omar Mahroo, Rachel M Huckfeldt, Sarah Firman, Eleanor Baldwin, Kristie DeMarco, Susan Kuranoff, Amena Fine, Reinhard Klingel, Sacha Ferdinandusse, Joseph G Hacia, Ronald J Wanders, Anthony S Wierzbicki

Journal: Journal of inherited metabolic disease 2026;49(3):e70201

PMID: 42161578

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Abstract

Adult Refsum disease (ARD; OMIM 266510) is a degenerative autosomal recessive condition typically diagnosed in adulthood. It affects visual, auditory and nervous system function. It is characterised by plasma, neuro-ophthalmological and adipose tissue accumulation of the dietary-derived phytanic acid (PA). This guidance reviews the clinical aspects of ARD and discusses interventions to address various co-morbidities of the disease. This GRADE-aligned guidance is based on a review of the literature and a consensus statement reflecting the conclusions of professionals with experience in the diagnosis and management of ARD. This statement reviews clinical aspects of ARD and discusses current and potential interventions to address various symptoms of the disease. It provides an overview of the clinical phenotype, reviews the clinical, biochemical, and genetic findings in ARD, and the neurological and ophthalmological investigations needed at diagnosis and during follow-up. It highlights the importance of dietary management and its role in situations such as acute hospital admissions for inter-current illness. Furthermore, it provides guidance on the acute management of decompensation in ARD and outlines when therapeutic plasma exchange/lipoprotein plasmapheresis should be considered. Greater clinician and patient awareness will lead to early diagnosis and improved outcomes. Implementation of a low PA diet before further end organ involvement offers the best prognosis. Life-long dietary therapy, along with therapeutic plasma exchange/lipoprotein apheresis during acute decompensations, remains the mainstay of management. Patients should have access to a multidisciplinary team to ensure specialist dietary input and supportive management of comorbidities.

Address: Department of Adult Inherited Metabolic Diseases, Guy's & St Thomas' Hospitals NHS Foundation Trust, London, UK.; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Ophthalmology & Center for Medical Genetics, Ghent University Hospital & Department of Head & Skin, Ghent University, Ghent, Belgium.; Moorfields Eye Hospital, London, UK.; Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts, USA.; Global DARE Foundation, Windham, Maine, USA.; Department of Neurology Kennedy-Krieger Institute, Johns Hopkins Hospital, Baltimore, Maryland, USA.; Apheresis Research Institute, Cologne, Germany and First Department of Internal Medicine, University Hospital Mainz, Cologne, Germany.; Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, the Netherlands.; Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

DOI: 10.1002/jimd.70201

MeSH Terms: Humans, Refsum Disease, Adult, Disease Management, Phytanic Acid