Clinical characteristics: Adult Refsum disease (ARD is associated with elevated plasma phytanic acid levels, late childhood-onset (or later) retinitis pigmentosa, and variable combinations of anosmia, polyneuropathy, deafness, ataxia, and ichthyosis. Onset of symptoms ranges from age seven months to older than age 50 years. Cardiac arrhythmia and heart failure caused by cardiomyopathy are potentially severe health problems that develop later in life.
Diagnosis/testing: The diagnosis of ARD is established in a proband with suggestive clinical and biochemical findings by identification of biallelic pathogenic variants in either PHYH or PEX7 on molecular genetic testing.
Management: Treatment of manifestations: Plasmapheresis or lipid apheresis to decrease phytanic acid levels is used only for acute arrhythmias or extreme weakness. Dietary restriction of phytanic acid intake helps resolve ichthyosis, sensory neuropathy, and ataxia. A high-calorie diet and avoidance of fasting prevent mobilization of phytanic acid stored in adipose tissue into the plasma. Hypercaloric parenteral infusions are required during periods of severe illness or postoperatively. Supportive treatment includes hydrating creams for ichthyosis and drugs for cardiac arrhythmias and cardiomyopathy.
Agents/circumstances to avoid: Food products containing phytanic acid, mostly from ruminants (cow, sheep, goat), some fish and walnuts; fasting and/or sudden weight loss; use of either ibuprofen or amiodarone.
Evaluation of relatives at risk: Testing of sibs of a proband ensures early treatment to reduce plasma phytanic acid concentration before symptoms occur.
Genetic counseling: ARD is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a PHYH or PEX7 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the PHYH or PEX7 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, molecular genetic prenatal testing, and preimplantation genetic testing for ARD are possible.
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