Refsum Syndrome: Causes, Symptoms & Treatment

Refsum syndrome is understood by physicians to be a hereditary and relapsing metabolic disorder. Symptoms affect the internal organs, central nervous system, peripheral nervous system, and skeleton, as well as the skin. The disease is largely arrested via a low phytanic acid diet and plasmapheresis.

What is refsum syndrome?

Refsum syndrome, or Refsum-Kahlke disease, is a condition known as heredoataxia. The condition is also known as Refsum-Thiébaut disease, heredopathia atactica polyneuritiformis, or Refsum disease. Heredoataxias are genetic diseases of the central nervous system. The leading symptoms of these diseases are ataxias, i.e. disorders of the musculoskeletal system. Refsum syndrome is caused by a peroxisomal metabolic disorder. The peroxisomes serve to break down metabolites in the body. In Refsum’s disease, this degradation is disturbed. Phytanic acid therefore accumulates and leads to ataxic consequences in particular. The Norwegian Sigvald Refsum documented the disease for the first time in the 20th century and became its namesake. Refsum’s snydrome is often also referred to as hereditary and motor-sensitive neuropathy.

Causes

The biochemical cause of Refsum disease is the accumulation of phytanic acid. This is a saturated and branched-chain fatty acid that humans ingest with food. To break down this fatty acid, peroxisomal α-oxidation serves. This process is regulated by the enzyme phytanoyl-CoA hydroxylase. A defect in this metabolic enzyme manifests as Refsum syndrome. However, defects of the transport protein peroxin-7 can also be causative for Refsum’s disease. The protein peroxin-7 is responsible for the transport of phytanol-CoA hydroxylase, which makes phytanic acid degradation possible in the first place. Refsum disease is thus a genetically heterogeneous disease. Usually, a defect of chromosome ten is related to the defect of the transport protein or metabolic enzyme. The disease is passed on in autosomal recessive inheritance. That is, both homologous chromosomes must carry the defect for onset to occur.

Symptoms, complaints, and signs

Both the sense of sight and the central nervous system, skeletal system, and organ system may experience symptoms in Refsum disease. Night blindness is the most common early symptom. Most often, patients suffer from progressive retinal pigmentosa. That is, their retinal cells degenerate. This degeneration is accompanied by visual field loss and, later, partial blindness. Uncontrolled eye movements and sudden lens opacities may also occur. Patients’ skin often suffers from keratinization disorders. Some patients also lose their sense of smell, suffer from gait unsteadiness, or lose their sense of spatial orientation. Intention tremor and hearing loss sometimes accompany the above symptoms. Equally typical manifestations of the metabolic disorder are failures of tendon reflexes or damage to the peripheral nervous system. The skeletal system is sometimes affected by deformities, such as deformities of the toe or pathologically pronounced foot curvatures. In addition, cardiac arrhythmias or bladder defects may occur.

Diagnosis and course of the disease

Physicians diagnose Refsum syndrome by detecting phytanic acid in the urine and plasma. The disease is relapsing progressive. An episode may be followed by a period of relative absence of symptoms. As a rule, however, the symptoms do not disappear completely. Only partial remissions are conceivable. Acute worsening of the disease occurs, for example, in the context of metabolic stress. Remarkable worsening may also occur during infections, during periods of reduced caloric intake, or during pregnancy.

Complications

Various complications and late effects occur during the course of Refsum disease. Degeneration of retinal cells is associated with visual field loss, visual disturbances, and, later, often complete blindness. Cornification disorders may occur in the skin. Some patients suffer from gait instability and coordination disorders – both of which can cause accidents and falls. Furthermore, loss of the sense of smell and hearing loss may occur. In the further course, the metabolic disorder causes damage to the peripheral nervous system and failures of tendon reflexes.In severe cases, deformations of the skeletal system occur. The affected person then suffers, for example, from pathologically pronounced foot curvatures or deformations of the toe. Cardiac arrhythmias and bladder defects are also typical complications. Therapy of the refsum syndrome involves the risk of side effects and interactions due to administered drugs. If the patient has to be treated via blood washing, this can be accompanied by infections, damage to the vessels and heart disease. Kidney damage cannot be ruled out either. If the metabolic disorder is treated surgically, which is particularly necessary in the case of malformations, inflammation, bleeding, secondary bleeding and nerve injury may occur. After surgery, wound healing disorders may develop or scars may form.

When should you see a doctor?

Refsum syndrome should always be treated by a doctor. There is no self-healing in this disease and in most cases also a deterioration of the general condition of the affected person, if no treatment is initiated. The means of self-help are also relatively limited in this case. A doctor should be consulted for refsum syndrome if the affected person suffers from various visual field defects. In the worst case, this can also lead to blindness. Hearing loss can also be an indication of the syndrome and should be examined by a doctor if it occurs over a long period of time and does not disappear on its own. Since refsum syndrome is also associated with heart problems, the affected person should have regular checkups. Diagnosis and treatment of the Refsum syndrome can be done by a general practitioner or by an ophthalmologist. Special complications usually do not occur.

Treatment and therapy

In an acute phase, refsum syndrome is usually treated via plasmapheresis. In this process, a machine similar to a dialysis machine filters the abnormal substances from the blood and then returns the patient’s own blood to the patient. If there is currently no relapse, a low phytanic acid diet serves to delay the relapse. In most cases, this diet brings the disease to a virtual standstill. Humans consume an average of 100 milligrams of phytanic acid daily. Under the diet, patients of Refsum’s snydrome consume only about ten milligrams of phytanic acid per day. Dairy products and the meat of ruminants are usually eliminated altogether, as they contain the most phytanic acid. To block mobilization from adipose tissue, a balanced caloric intake is important. Often the special diet of patients is combined with the administration of vitamins A, C and E. Usually, these measures allow skin changes to heal and neuopathies to partially or completely regress. Changes in the sense of sight and smell may not disappear as a result of the diet. On the other hand, they often do not progress through the dietary measures. The doctor regularly checks the phytanic acid concentration in the blood. If the concentration cannot be reduced by the above measures, plasmapheresis may sometimes be indicated even in non-acute phases. Refsum syndrome is not yet curable, since there are no causal but only symptomatic therapies available. Depending on the symptoms, the physician may carry out additional therapeutic measures. In the case of skin lesions, for example, dermatological products can be used to alleviate the symptoms.

Prevention

Refsum disease cannot be prevented to date. Either a person carries the genetic defect or does not carry it. However, not every defect must result in an outbreak of the disease. At least severe episodes of Refsum disease can be prevented. For example, carriers of the defect should avoid metabolic stress.

Aftercare

Affected individuals with Refsum syndrome usually have very few and also very limited measures of direct aftercare available to them, so ideally a doctor should be consulted early on and treatment initiated for this disease. Since this is a genetic disease, there is no independent cure. In the case of a renewed desire to have children, a genetic examination and consultation should also be carried out in order to prevent the recurrence of Refsum syndrome in the descendants. The treatment of the Refsum syndrome is mostly done by the measures of a physiotherapy or a physiotherapy.Sufferers can also repeat many of the exercises at home and thus accelerate the healing process. Most of those affected by the Refsum Syndrome are dependent on taking medication. All the doctor’s instructions should be followed. Likewise, the prescribed dosage and also the regular intake should be observed. In many cases, the disease also significantly reduces the life expectancy of the affected person.

This is what you can do yourself

First and foremost, a consistent diet low in phytanic acid must be followed for refsum syndrome. Affected individuals should not consume more than 10 milligrams of phytanic acid per day. This can be achieved by following a diet that is low in beef and dairy products and instead includes foods rich in vitamins and fiber. At the same time, care must be taken to ensure adequate caloric intake. This prevents uncontrolled mobilization of phytanic acid in the fat cells. In addition, general measures such as sufficient exercise and the avoidance of stress apply. Affected people must pay attention to the physical warning signals. If unusual symptoms occur despite the diet, a visit to the doctor is recommended. Since refsum syndrome is a metabolic disease, a controlled diet is the best way to treat the disease. However, medications must always be taken as well. The physician should be informed about any side effects of the prescribed drugs. After plasmapheresis, rest and bed rest apply. The exchange of blood plasma is an enormous strain on the body and therefore requires good aftercare. Patients with mild symptoms may also resort to homeopathic remedies if necessary.