Patients with Refsum disease do not generally show any obvious defects at birth except maybe short metacarpals and metatarsals (shorten thumbs or shorten 4th toes). Other bones and joints may be affected, but growth and development appear normal. Initial symptoms will generally appear between the age of 10 to 20 or possibly earlier with the loss of night vision being common.  Patients have also been known to not display any significant symptoms until around age 50. The initial complaints usually involve vision problems, a poor sense of smell and as phytanic acid accumulates weakness in the arms and legs or unsteadiness. Below is a list of the most common symptoms of Refsum disease.

 

• Retinitis pigmentosa: Retinitis pigmentosa is an expression of degenerative eye disease as the visual receptors are lost in the retina and the background structure of the eye is exposed. It manifests as a failure of night vision and later decreased peripheral vision, and eventually can lead to low vision or blindness.

• Anosmia: loss of the sense of smell and many aspects of the subtleties of taste

• Peripheral polyneuropathy: Peripheral polyneuropathy is the term for dysfunction of the nerves outside of the spinal cord. Symptoms may include numbness, weakness, burning pain, and loss of reflexes occurring initially at the body extremes (feet or hands).

• Deafness: loss of hearing

• Cerebellar ataxia: Ataxia is a nerve-derived form of unsteadiness. Cerebellar ataxia refers to the fact that the defect is in a specific part of the brain (the cerebellum) that coordinates muscle functions. As a result the brain fails to regulate the body posture, as well as the strength and direction of movements.

• Skeletal dysplasia: Bone abnormalities including shortening or deformity of the tubular bones in the hands and feet and abnormal growth plates (epiphyseal dysplasia) at the knees, elbows and shoulders may be found.

• Ichthyosis: A distinct type of scaliness of the skin different in appearance from eczema or psoriasis. These symptoms can range anywhere from fish-like scaliness of the palms and soles of the feet to being present on the trunk of the body.

• Pupillary abnormalities: The pupil of the eye is often small in Refsum disease and does not respond well to light or drugs used to ‘open’ the eye by optometrists.

• Cataract: a clouding of the lens in the eye causing deterioration in vision often associated with starburst haloes around bright objects.

• Nystagmus: rapid, involuntary, rhythmic eye movements

• Cardiac Arrhythmia: Heart rhythm abnormalities are a rare but serious complication of very high phytanic acid levels and can be a cause of death in Refsum disease.

• Weakness: significant slow-recovering weakness after illness is a feature of Refsum disease

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The impact on an individual of these symptoms can increase based on their plasma phytanic acid level.  Higher levels will generally increase the severity of symptoms. Phytanic acid accumulates in the fat tissue of Refsum patients throughout their lives before their diagnosis.  This means that even with a strict diet low in phytanic acid an individual can still have higher levels of plasma phytanic acid throughout their lives due to release of phytanic acid from their fat cells into their blood.