Refsum’s disease is a member of the leukodystrophies group and is characterised biochemically by an accumulation of phytanic acid. The prevalence of the disease is 1 case per 1,000,000; both sexes are affected.
The earliest symptom of Refsum’s disease is usually a gradual decrease in night vision (or night blindness). In the second stage (often after a few years), retinitis pigmentosa can lead to a narrowing of the visual field and to blindness. An –electroretinogram– (ERG) can help confirm the ophthalmologic diagnosis, which is otherwise difficult to make, especially in young children.
Loss of smell
Loss of smell is found in virtually all patients with Refsum’s disease when they undergo scent testing.
Patients with Refsum’s disease may have chronic sensory-motor polyneuropathy which is asymmetric and progressive in nature if not (sufficiently) treated. This polyneuropathy is not always evident when diagnosed with Refsum disease, due to relapses and remissions. It can cause long-term muscle atrophy and therefore a motor deficit not only of the lower limbs but also of the trunk. Most patients also have sensory disturbances.
It is a bilateral and symmetrical sensorineural hearing loss which involves high frequencies and conversational frequencies. This deafness can be moderate or severe.
The diagnosis can be confirmed if necessary, by auditory evoked potentials.
Cerebellar ataxia is generally considered to be one of the major clinical symptoms of Refsum’s disease, despite having a later clinical manifestation than those of retinitis pigmentosa and polyneuropathy. In particular, patients with cerebellar ataxia suffer from difficulty walking.
Ichthyosis is characterised by a build-up of scales that make the skin appear rough. It only affects a minority of patients with Refsum’s disease, who usually show the first signs during adolescence. A manifestation during infancy is less common.
Complications of cardiomyopathy, such as arrhythmias or heart failure, are often the cause of death of patients with Refsum’s disease.
Adult Refsum’s disease
In 1945, Prof. Refsum described a pathology that would later be known as Refsum’s disease.
This condition combines night blindness, lack of smell, deafness, poor coordination (ataxia), numbness and weakness of the legs (due to “peripheral neuropathy”) and dry skin with scaling (ichthyosis). The first symptoms usually appear in the second decade of life, after which they progress.
It was later discovered that this disease is due to an abnormality affecting the degradation (alpha oxidation) of phytanic acid, which results in the accumulation of phytanic acid (saturated fatty acid) in all the tissues of the organization.
Phytanic acid is derived from phytol, which is found in green vegetables, plankton, and animals that consume (and can digest) the following foods: meat of cattle and other ruminant animals, many dairy products, or Fish. It was discovered in 1988 that the consumption of green vegetables is safe (since humans, unlike ruminants, do not digest the chlorophyll which contains phytol).
The treatment of Refsum’s disease therefore consists mainly of following a diet low in phytanic acid, since all of the phytanic acid is of exogenous origin (that is to say, it comes from what we eat). If phytanic acid levels drop, the disease stabilizes (at least the symptoms of ichthyosis, ataxia and neuropathy).
It is also important for patients with Refsum’s disease not to lose weight quickly, as weight loss can release large amounts of phytanic acid from fat stores in the body. Any weight loss must therefore be gradual.
The exploration of the induction of another way of degradation of phytanic acid (omega-oxidation) is underway and should allow the development of new treatments.