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

Refsum's disease in adults is a rare inherited disorder that causes the accumulation in the blood of a fatty acid that we get from some foods and whose consequences lead to injuries of varying degrees that affect sensory and motor functions, among others.

In this article we explain what Refsum's disease is and what its causes are, how it can be diagnosed, what are its main clinical signs and symptoms, as well as the indicated treatment.

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Adult Refsum's disease: what is it and how does it occur?

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

This hereditary disease is transmitted following 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 of the PAHX gene on chromosome 10.

Affected patients are unable to metabolize phytanic acid, a branched-chain saturated fatty acid. present, mainly, in foods such as ruminant meat and dairy products, as well as in fish to a lesser extent proportion. The accumulation of this compound causes damage to the retina, the brain and the peripheral nervous system.

The prevalence of Refsum's disease is 1 case per million inhabitants., and affects men and women equally, without racial or gender predominance. The initial symptoms usually begin around the age of 15, although they can also appear during childhood or in adulthood (between the ages of 30 and 40). Next, we will see what are 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 known as the classic triad of symptoms: retinitis pigmentosa, cerebellar ataxia, and distal sensorimotor polyneuropathy.

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

Beyond these three typical symptoms, in Refsum's disease there may also be involvement of the cranial nerves, cardiac, dermatological and skeletal problems. At the sensory level, anosmia (decrease or loss of smell), hearing loss, corneal opacities (causing loss of vision and photosensitivity) and skin changes. Other clinical manifestations also present in the disease are: cataracts, ichthyosis (the skin becomes dry and scaly) and anorexy.

Patients who are not treated or who are diagnosed late can present severe neurological damage and develop depressive disorders; in these cases, there is a high percentage of mortality. Besides, it is important that the patient maintains a correct diet to attenuate neurological, ophthalmological and cardiac symptoms.

Diagnosis

The diagnosis of adult Refsum's disease is made by determining the accumulation of high concentrations of phytanic acid in blood plasma and urine. Plasma long-chain fatty acid levels indicate metabolic defects and can serve as an indicator. In any case, a physical examination and a biochemical evaluation are necessary, although the clinician must rely on typical signs and symptoms..

The histopathological diagnosis (study of the affected tissues) shows hyperkeratosis, hypergranulosis and acanthosis in the skin. The pathognomonic lesions are found in the basal and suprabasal cells of the epidermis, which show vacuoles of different sizes with evident accumulation of lipids.

It is important to diagnose the disease as early as possible, since a timely start of nutritional treatment can stop or delay many of its clinical manifestations.

Differential diagnosis includes: Usher syndrome I and II; individual enzymatic defects in peroxisome fatty acid beta-oxidation; disorders with severe hypotonia; neonatal seizures; and liver dysfunctions or leukodystrophy. In addition, adult Refsum's disease should not be confused with the childhood variant (infantile Refsum's disease).

Treatment

Nutritional treatment is usually indicated in Refsum's disease. As we have previously commented, since phytanic acid is obtained exclusively from food, a strict diet with restriction of Fats present in certain ruminant meats and fish (tuna, cod or haddock) can help prevent the progression of the symptoms of 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 buildup and excess phytanic acid is filtered off; and, finally, the renewed blood plasma is reinfiltrated into the patient.

So far, no drugs have been found capable of inducing an enzymatic activity that promote the degradation of phytanic acid and reduce its concentration in blood plasma, therefore that At present, research continues in the search for more effective treatments to combat this and other similar diseases..

Bibliographic references:

• Castro, F., & del Socorro, Á. (2009). Clinical case: nutritional treatment of a genetic disorder called Refsum Syndrome. Perspectives in Human Nutrition, 11(2), 205-210.

• Wanders, R. J., Waterham, H. R., & Leroy, B. Q. (2015). Refsum disease. In GeneReviews®[Internet]. University of Washington, Seattle.