Refsum Disease Workup

Updated: May 22, 2020
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD  more...
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Laboratory Studies

In Refsum disease (RD), the phytanic acid level in the blood is increased. The normal range is equal to or less than 0.2 mg/dL; however, phytanic acid levels are 10-50 mg/dL or even higher in patients with Refsum disease.

Cerebrospinal fluid (CSF) shows an albuminocytologic dissociation with a protein level of 100-600 mg/dL.

Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels are decreased.

Routine laboratory investigations of blood and urine do not reveal any consistent diagnostic abnormalities.


Imaging Studies

Skeletal radiography is required to estimate bone changes.

MRI findings could reveal symmetrical signal changes involving the corticospinal tracts, cerebellar dentate nuclei, and corpus callosum. [22]

Proton nuclear magnetic resonance (1 H-NMR) spectroscopy of blood plasma or serum lipid extracts can be used to correctly identify and quantify lipids, including unusual lipids in the blood of patients with inborn errors of lipid metabolism, which could be applicable in clinical diagnosis and follow up.


Other Tests

Phytanic oxidase activity estimation in skin fibroblast cultures is important.

Electrocardiogram (ECG) is helpful to rule out cardiac conduction defect.

UPSIT (University of Pennsylvania Smell Identification Test) reveals anosmia or grossly impaired smell function. [23]

Urine acylcarnitine analysis by nuclear magnetic resonance electrospray ionization-MS/MS seems to be a new tool for the diagnosis of peroxisomal biogenesis disorders. [24]


Histologic Findings

Skin biopsy shows features of ichthyosis vulgaris, such as moderate hyperkeratosis and acanthosis with thin granular layer. Variably sized vacuoles are visible in basal and suprabasal keratinocytes. The lipid stains performed on cryostat cut sections revealed presence of lipid accumulation in vacuoles. Nerve biopsy examination shows nerve demyelination with marked Schwann cell proliferation and onion bulb formation.

Ultrastructural skin examination reveals many intracellular non–membrane-bound vacuoles in the basal layer and less numerous in keratinocytes of suprabasal epidermis. Transmission electron microscopy does not reveal changes of keratohyalin observed in dominant ichthyosis vulgaris.