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

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.