Long‐term strategies for the treatment of Refsum's disease using therapeutic apheresis

Abstract

Refsum's disease is a rare autosomal recessive disorder of fatty acid metabolism. Poorly metabolized phytanic acid accumulates in fatty tissues, including myelin sheaths and internal organs, leading to retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia, and renal, cardiac or liver impairment. Dietary restriction of phytanic acid in some cases is not sufficient to prevent acute attacks and stabilize the progressive course. Phytanic acid bound to large low density lipoproteins (LDL) and very low density lipoproteins (VLDL) molecules offers the possibility of extracorporeal elimination by lipid apheresis. We report on the long-term lipid apheresis treatment of four patients with severe Refsum's disease. Retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia, anosmia, and sensorineural hearing loss were major symptoms exhibiting a progressive course. Lipid apheresis was performed for 5-13 years without severe complications. Maximum levels of phytanic acid before commencing chronic lipid apheresis were >300 mg/l. During steady state with lipid apheresis, mean phytanic acid before treatments was 87 mg/l and was reduced to 36 mg/l. Mean reduction rate was 59% per treatment. In all patients, abnormal motor nerve conduction velocity with signs of chronic denervation improved, morphological and functional stabilization of eye involvement was observed. Lipid apheresis prevented the extension of the disease to previously unaffected organs in three patients. Extracorporeal elimination of lipoprotein-phytanic acid complexes by lipid apheresis represents a pathophysiologically guided therapeutic approach, resulting in long-term improvement or stabilization of overall rehabilitation in patients with progressive Refsum's disease.

Therapeutic hepatocyte transplant for inherited metabolic disorders: functional considerations, recent outcomes and future prospects

“…Additional treatment options include administration of dermatological drugs that soften the skin and ultimately upregulate α-hydroxylation of phytanic acid to a limited extent. OLT decreases phytanic acid and very long chain fatty acids in serum and improves elimination of abnormal plasma bile acids (Van Maldergem et al 2005)(Zolotov et al 2012). …”

The Challenges of a Successful Pregnancy in a Patient with Adult Refsum’s Disease due to Phytanoyl-CoA Hydroxylase Deficiency

“…Dietary restriction lowers plasma phytanic acid levels by 50-100%, leading to significant improvement in neurological function (Baldwin et al 2010). Acute or long-term plasmapheresis is also used in the management of ARD (Kohlschutter et al 2012;Zolotov et al 2012). Although visual loss, anosmia and deafness are irreversible, their progression may slow with dietary therapy (Baldwin et al 2010).…”

Treatable inherited rare movement disorders

“…It is caused by deficiency of the enzyme phytanyl CoA hydroxylase, which is required for metabolism of branched chain fatty acids such as phytanic acid. A diet reduced in phytanic acids can prevent or reverse symptoms in Refsum disease …”