Refsum Disease (adult): Diagnosis, Symptoms, Causes And Treatment
Refsum disease in adults is a rare hereditary disorder that causes the accumulation in the blood of a fatty acid that we obtain from some foods and whose consequences lead to lesions of varying degrees that affect sensory and motor functions, among others.
In this article we explain what Refsum 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.
Refsum disease in adults: what is it and how does it occur?
Refsum disease, named after 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 lipidoses, 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 disease is caused by a deficiency of the peroximal enzyme phytanol CoA hydroxylase (PAHX), 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. The accumulation of this compound causes damage to the retina, brain and peripheral nervous system.
The prevalence of Refsum disease is 1 case per million inhabitants, and affects men and women equally, without racial or gender predominance. Initial symptoms usually begin around age 15, although they can also appear during childhood or adulthood (between 30 and 40 years). Next, we will see what the main signs and symptoms of this disease are.
Signs and symptoms
The first signs and symptoms of adult Refsum disease 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 predominantly 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 produces loss of sensitivity and paresthesias (tingling and numbness sensations) in the patient.
Beyond these three typical symptoms, in Refsum disease there may also be involvement of the cranial nerves, cardiac, dermatological and skeletal problems. At a sensory level, anosmia (decrease or loss of smell), hearing loss, corneal opacities (causing loss of vision and photosensitivity) and skin alterations 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 who are diagnosed late can present serious neurological damage and develop depressive disorders; In these cases, there is a high mortality rate. Besides, It is important that the patient maintains a correct diet to alleviate neurological, ophthalmological and cardiac symptoms
The diagnosis of adult Refsum disease is made by determining the accumulation of high concentrations of phytanic acid in the blood plasma and urine. Plasma levels of long-chain fatty acids indicate that metabolic defects exist and may serve as an indicator. In any case, it is necessary to perform a physical examination and a biochemical evaluation, although the clinician must rely on the 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 lipid accumulation.
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.
The differential diagnosis includes: Usher syndrome I and II; individual enzymatic defects in peroxisomal fatty acid beta-oxidation; disorders with severe hypotonia; neonatal seizures; and liver dysfunctions or leukodystrophy. Furthermore, Refsum disease in adults should not be confused with the childhood variant (childhood Refsum disease).
Treatment
Nutritional treatment is usually indicated in Refsum disease As we have mentioned previously, because 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 symptoms of phytanic acid. the illness.
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 that is used in autoimmune diseases and serves to purify blood plasma; First, the patient’s blood is drawn; The buildup and excess phytanic acid is then filtered out; and finally, the renewed blood plasma is infiltrated back into the patient.
To date, no drugs have been found capable of inducing enzymatic activity that promotes the degradation of phytanic acid and reduces its concentration in the blood plasma, so Currently, research continues in the search for more effective treatments to combat this and other similar diseases
