Refsum Syndrome

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Clinical Refsum Syndrome/Phytanic acid storage disease/Heredopathia atactica polyneuritiformis

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Synonym

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Phytanic acid storage disease; Heredopathia atactica polyneuritiformis

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Inheritance

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Autosomal recessive; PAHX gene on 1 Op, PEX7 gene on 6q

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Prenatal

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CVS/amniocentesis: phytanic acid oxidase assay on cultured cells; DNA analysis

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Incidence

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Rare; approximately 100 cases reported; M~F

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Age at Presentation

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Neurologic symptoms start in childhood; cutaneous changes usually occur as an adult

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Pathogenesis

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Mutations in the PAHX gene create a deficiency in phytanoyl CoA hydroxylase, a peroxisomal enzyme responsible for the catalyzation of phytanic acid; deficient enzyme leads to an accumulation of phytanic acid in serum and replacement of the normal fatty acids in epidermal lipids and other tissues throughout the body; can also be caused by mutations in the PEX7 gene that encodes peroxin 7, a receptor important in targeting enzymes to peroxisomes; defective PEX7 leads to a deficiency in multiple peroxisomal enzymes

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Clinical

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Skin
Mild ichthyosis (i.e., ichthyosis vulgaris) usually beginning after neurologic symp
tornatology

Central Nervous System
Cerebellar ataxia, progressive peripheral polyneuropathy

Eyes
Retinitis pigmentosa with salt and pepper pigment, secondary night blindness

Ear Nose Throat
Sensorineural deafness

Cardiac
.Arrhythmias with heart block, cardiac failure

Musculoskeletal
Symmetric muscular wasting, variety of skeletal anomalies

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D/Dx

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Peroxisomal deficiency disorders
lchthyosis vulgaris (p. 2)
Vitamin B deficiency

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Lab

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increased serum phytanic acid; decreased phytanic acid oxiclase activity in cultured
fibroblasts
Skin biopsy revealing lipid filled vacuoles in basal keratinocytes
increased cerebrospinal fluid (CSF) protein without cells

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MAnagement

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Dietary restriction of phytanic acid decrease green vegetables, dairy products and
ruminant fats
Plasma exchange removal of phytanic acid
Referral to neurologist, ophthalmologist, cardiologist, dermatologist, otolaryngologist,
and physiatrist

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Prognosis

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If diet and exchange instituted early on, progression of disease can be halted; if untreated, symptornatology is progressive with remissions and exacerbations culminating in premature sudden death from cardiac arrythmias (heart block) or respiratory failure (medullary depression)