Refsum’s disease (adult): diagnosis, symptoms, causes and treatment

Refsum’s disease in adults is a strange inherited disease that causes a fatty acid to build up in the blood that we get from certain foods and the consequences lead to injuries to varying degrees that affect sensory functions and motor, including others.

In this article we tell you what Refsum disease is and what are its causes, How to diagnose it, what are its main clinical signs and symptoms, and the treatment indicated.

    Refsum disease in adults: what is it and how does it occur?

    Refsum’s disease, named after Norwegian neurologist Sigvald B. Refsum, is a rare metabolic syndrome characterized by the buildup of phytanic acid in the blood and tissues, including the brain. It belongs to the group of lipidosis, a group of inherited diseases that have in common the accumulation of harmful amounts of lipids (fats) in certain cells of the body.

    This inherited disease is transmitted in an autosomal recessive pattern; that is, for a person to inherit the disorder, they must receive a copy of the genetic mutation from both parents. Refsum’s disease is caused by a deficiency of the peroximal phytanol CoA hydroxylase (PAHX) enzyme, caused by a mutation in the PAHX gene on chromosome 10.

    Affected patients are unable to metabolize phytanic acid, a branched-chain saturated fatty acid found mainly in foods such as ruminant meat and dairy products, as well as in fish in smaller proportions. The build-up of this compound damages the retina, brain, and peripheral nervous system.

    The prevalence of Refsum’s disease is 1 case per million population, And affects both men and women, without racial or sexual predominance. The first symptoms usually start around the age of 15, although they can also appear during childhood or adulthood (between 30 and 40). Next, we will look at the main signs and symptoms of this disease.

    Signs and symptoms

    The first signs and symptoms of Refsum’s disease in adults appear between the end of the first decade of life and adulthood, and the person develops what is called the classic choice of symptoms: retinitis pigmentosa, cerebellar ataxia and predominantly distal sensorimotor polyneuropathy.

    Retinitis pigmentosa causes an abnormal accumulation of pigment in the retinal membrane, which triggers long-term retinal degeneration due to chronic inflammation; cerebellar ataxia involves a lack or deficit in the coordination of muscle movements, mainly in the hands and legs; and sensorimotor polyneuropathy produces loss of sensation and paresthesia (tingling and numbness sensations) in the patient.

    Beyond these three typical symptoms, in Refsum’s disease there can also be damage to the cranial nerves, heart problems, skin problems and skeletal problems. At the sensory level, anosmia (decrease or loss of smell), hearing loss, corneal opacity (resulting in loss of vision and photosensitivity) and skin changes can occur. Other clinical manifestations also present in the disease are: cataracts, ichthyosis (the skin becomes dry and scaly) and anorexia.

    Patients who are not treated or diagnosed late may present with severe neurological damage and develop depressive disorders; in these cases, the death rate is high. On another side, it is important for the patient to maintain an appropriate diet to relieve neurological, ophthalmic and cardiac symptoms.


    The diagnosis of Refsum’s disease in adults is made by determining the accumulation of high concentrations of phytic acid in the blood plasma and urine. Plasma levels of long chain fatty acids indicate that there are metabolic defects and can be used as an indicator. In all cases, a physical examination and biochemical evaluation should be performed, although the clinical professional should be based on typical signs and symptoms..

    Histopathological diagnosis (study of affected tissues) shows hyperkeratosis, hypergranulose and acanthosis of the skin. Pathognomonic lesions are found in the basal and suprabasal cells of the epidermis, which have vacuoles of varying sizes with obvious lipid accumulation.

    It is important to diagnose the disease as early as possible, as early initiation of nutritional therapy can slow or delay many of its clinical manifestations.

    The differential diagnosis includes: Usher syndrome I and II; individual enzymatic defects in the beta-oxidation of peroxisome fatty acids; disorders with severe hypotonia; neonatal seizures; and liver dysfunction or leukodystrophy. In addition, Refsum’s disease in adults should not be confused with the infantile variant (infantile Refsum’s disease).


    Nutritional treatment is generally indicated in Refsum’s disease. As mentioned above, because phytic acid is obtained exclusively from food, a strict diet with restriction of the fats present in certain meats and fish from ruminants (tuna, cod or haddock) can help prevent the progression of diseases. symptoms of the disease.

    This type of treatment successfully resolves symptoms such as ichthyosis, sensory neuropathy, and ataxia. Although the effects on the progression of others, such as retinitis pigmentosa, anosmia or hearing loss, seem more uncertain and these symptoms tend to persist.

    Another alternative procedure is plasmapheresis, a technique used in autoimmune diseases and used to purify blood plasma; first, the patient’s blood is drawn; then, the accumulation and excess of phytic acid are filtered; and finally, the renewed blood plasma is reinfiltrated into the patient.

    To date, no drug has been found to induce an enzymatic activity that promotes the degradation of phytanic acid and reduces its concentration in blood plasma, therefore research is currently underway to find more effective treatments to fight this disease and other similar diseases.

    Bibliographical references:

    • Castro, F., and Socors, To. (2009). Clinical case: nutritional treatment of a genetic disease called Refsum syndrome. Perspectives in Human Nutrition, 11 (2), 205-210.

    • Wanders, RJ, Waterham, HR and Leroy, BP (2015). Refsum disease. A GeneReviews®[Internet]. University of Washington, Seattle.

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