Refsum Syndrome

By | June 8, 2022

Doctors understand Refsum syndrome to be a hereditary and relapsing metabolic disorder. The symptoms affect the internal organs, the central nervous system, the peripheral nervous system and the skeleton as well as the skin. The disease comes to a standstill as far as possible via a low-phytic acid diet and plasmapheresis.

What is Refsum Syndrome?

Refsum syndrome or Refsum-Kahlke disease is a so-called heredoataxia. The condition is also known as Refsum-Thiébaut disease, heredopathia atactica polyneuritiformis or Refsum’s disease. Heredoataxias are genetic diseases of the central nervous system. The main symptoms of these diseases are ataxia, i.e. disorders of the musculoskeletal system. For meanings of li-fraumeni syndrome, please visit

The Refsum syndrome is caused by a peroxisomal metabolic disorder. The peroxisomes are used in the body to break down metabolites. In Refsum’s disease, this breakdown is disturbed. Phytanic acid therefore accumulates and in particular has atactic consequences. The Norwegian Sigvald Refsum documented the disease for the first time in the 20th century and gave it its name. Refsum’s syndrome is often referred to as a hereditary and motor-sensitive neuropathy.


The biochemical cause of Refsum’s disease is the accumulation of phytanic acid. It is a saturated, branched-chain fatty acid that humans ingest with food. Peroxisomal α-oxidation is used to break down this fatty acid. This process is regulated by the enzyme phytanoyl-CoA hydroxylase. A defect in this metabolic enzyme manifests itself as Refsum’s syndrome. However, defects in the transport protein peroxin-7 can also be the cause of Refsum’s disease.

The protein peroxin-7 is responsible for the transport of phytanol-CoA-hydroxylase, which enables the breakdown of phytanic acid. Refsum’s disease is such a genetically heterogeneous disease. A defect in chromosome ten is usually associated with a defect in the transport protein or the metabolic enzyme. The disease is passed on in an autosomal recessive inheritance. This means that both homologous chromosomes must carry the defect for the outbreak to occur.

Symptoms, Ailments and Signs

Both the sense of sight and the central nervous system, the skeletal system and the organ system can cause problems with Refsum’s disease. Night blindness is the most common early symptom. Most patients suffer from progressive retina pigmentosa. That means their retinal cells are degenerating. This degeneration is accompanied by visual field defects and later, in some cases, blindness.

Uncontrolled eye movements and sudden clouding of the lens can also occur. The skin of the patients often suffers from cornification disorders. Some patients also lose their sense of smell, suffer from unsteady gait or lose their sense of their own spatial position. Intentional tremor and hearing loss sometimes accompany these symptoms.

Equally typical manifestations of the metabolic disorder are failures of the tendon reflexes or damage to the peripheral nervous system. The skeletal system is sometimes affected by deformities, such as deformities of the toe or pathological foot arches. In addition, cardiac arrhythmias or bladder defects can occur.

Diagnosis and course of the disease

The doctor diagnoses Refsum’s syndrome by detecting phytanic acid in the urine and plasma. The disease progresses in spurts. A flare-up can be followed by a period of relative ease. However, the symptoms usually do not disappear completely. Only partial remissions are conceivable. Acute worsening of the disease occurs, for example, in the context of metabolic stress. A noticeable deterioration can also occur in the case of infections, in times of reduced calorie intake or during pregnancy.


In the course of Refsum’s disease, various complications and late effects occur. The degeneration of the retinal cells is accompanied by loss of visual field, visual disturbances and later often also with complete blindness. Cornification disorders can occur in the skin area. Some patients suffer from unsteady gait and coordination disorders – both of which can cause accidents and falls.

Loss of smell and hearing loss can also occur. In the further course, the metabolic disorder causes damage to the peripheral nervous system and failure of the tendon reflexes. In severe cases, there is deformation of the skeletal system. The affected person then suffers, for example, from pathologically pronounced foot arches or deformations of the toe.

Cardiac arrhythmias and bladder defects are also typical complications. The therapy of Refsum’s syndrome harbors the risk of side effects and interactions from the medication administered. If the patient has to be treated via blood washing, this can be associated with infections, damage to the vessels and heart diseases. Kidney damage cannot be ruled out either.

If the metabolic disorder is treated surgically, which is necessary above all in the case of malformations, inflammation, bleeding, secondary bleeding and nerve injuries can occur. After the operation, wound healing disorders can occur or scars can form.

When should you go to the doctor?

Refsum syndrome should always be treated by a doctor. This disease does not heal on its own and in most cases the general condition of the person affected deteriorates if no treatment is initiated. The means of self-help are also relatively severely limited.

A doctor should be consulted for Refsum syndrome if the person affected suffers from various visual field defects. In the worst case, it can also lead to blindness. Hearing loss can also indicate the syndrome and should be examined by a doctor if it occurs over a longer period of time and does not go away on its own. Since Refsum syndrome is also associated with heart problems, the affected person should be examined regularly.

The diagnosis and treatment of Refsum syndrome can be carried out by a general practitioner or by an ophthalmologist. Special complications usually do not arise.

Treatment & Therapy

In an acute phase, Refsum syndrome is usually treated with plasmapheresis. A machine similar to a dialysis machine filters the pathological substances out of the blood and then feeds the patient’s own blood back into the blood. If there is currently no relapse, a low-phytanic acid diet serves to delay the relapse. This diet brings the disease to a standstill in most cases. Humans take in an average of 100 milligrams of phytanic acid every day.

As part of the diet, patients with Refsum syndrome only consume around ten milligrams of phytanic acid per day. Dairy products and ruminant meat are usually eliminated entirely because they contain the most phytanic acid. A balanced calorie intake is important to block mobilization from the adipose tissue. The special diet of the patients is often combined with the administration of vitamins A, C and E. Normally, these measures allow skin changes to heal and neuopathies to partially or completely recede.

The changes in vision and smell may not reverse with the diet. On the other hand, they often do not progress any further with the dietary measures. The doctor regularly checks the concentration of phytanic acid in the blood. If the concentration cannot be lowered by the measures mentioned, plasmapheresis may sometimes be indicated even in non-acute phases.

So far, Refsum’s syndrome cannot be cured, since no causal therapies are available, only symptomatic therapies. Depending on the symptoms, the doctor may carry out additional therapy measures. In the case of skin changes, for example, dermatological products can alleviate the symptoms.


So far, Refsum’s disease cannot be prevented. A person either carries the genetic defect or does not carry it. However, not every defect has to result in an outbreak of disease. At least severe flare-ups can be prevented in Refsum’s disease. Carriers of the defect should avoid metabolic stress, for example.


Affected people with Refsum syndrome usually only have very few and only very limited measures of direct aftercare available, so that ideally a doctor should be consulted at an early stage and treatment should be initiated. Since this is a genetic disease, it cannot heal on its own.

If you want to have children again, a genetic examination and counseling should also be carried out in order to prevent the recurrence of Refsum syndrome in the offspring. The treatment of Refsum’s syndrome is usually carried out by means of physiotherapy or physiotherapy. Those affected can also repeat many of the exercises at home and thus accelerate healing.

Most of those affected by Refsum syndrome are dependent on taking medication. All doctor’s instructions should be followed. The prescribed dosage and regular intake must also be observed. In many cases, the life expectancy of those affected is also significantly reduced by the disease.

You can do that yourself

In the case of Refsum syndrome, a consistent low-phytanic acid diet must be adhered to in the first place. Affected people should not consume more than 10 milligrams of phytanic acid per day. This can be achieved through a diet that is low in beef and dairy products and instead includes foods rich in vitamins and fiber. At the same time, a sufficient calorie intake must be ensured. This avoids an uncontrolled mobilization of phytanic acid in the fat cells.

In addition, general measures such as sufficient sport and the avoidance of stress apply. Affected people must pay attention to the physical warning signals. If unusual symptoms occur despite the diet, it is advisable to consult a doctor. Because Refsum’s syndrome is a metabolic disease, a controlled diet is the best way to treat the disease. However, medication must always be taken. The doctor should be informed about any side effects of the prescribed preparations.

Rest and bed rest apply after plasmapheresis. The exchange of blood plasma represents an enormous burden for the body and accordingly requires good aftercare. Patients with mild symptoms can also resort to homeopathic remedies if necessary.

Refsum Syndrome