Introduction:
Refsum disease is a rare lipid (fat) metabolic (a chemical reaction in our body that helps to sustain life) disorder characterized by an abnormal build-up of fat (called phytanic acid) in blood plasma and tissues. Phytanic acid is obtained from diets like dairy products and animal-derived foods (beef, meat, and seafood). Normally phytanic acid is broken by alpha oxidation (the process of breakdown of fats in the body) within cell structures called peroxisomes. The mutation in the gene PHYH (Phytanoyl-CoA 2-Hydroxylase) and PEX7 (Peroxisomal Biogenesis Factor 7) gene (which helps in peroxisome functions is disrupted, leading to Refsum disease. Early signs of Refsum disease are loss of vision (retinitis pigmentosa), and loss of smell (anosmia) is observed in teenagers between the age of 10 to 20 years.
What Is the Prevalence of Refsum Disease?
The prevalence of Refsum disease is about one in one million people in the general population. Both females and males are affected equally.
What Are the Causes of Refsum Disease?
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Genetic Mutation: Refsum disease is a rare disorder caused by mutation of PHYH (Phytanoyl-CoA 2-Hydroxylase) and PEX7 (Peroxisomal Biogenesis Factor 7) gene resulting in disruption of peroxisomes that contains enzymes that break phytanic acid resulting in abnormal deposition of fat in tissues and blood plasma.
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Hereditary: If one of the parents has Refsum disease, there are increased chances of having a child with a similar disease.
What Are the Types of Refsum Disease?
It is of two types:
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Adult or Classical Refsum Disease: It occurs due to a deficiency of enzyme phytanoyl-CoA Hydroxylase (PAHX) encoded by gene PHYH (Phytanoyl-CoA 2-Hydroxylase), which disrupts peroxisomes functions to breakdown the fast resulting in an abnormal build-up of lipids.
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Infantile Refsum Disease: It occurs due to genetic mutation of PEX 1, PEX 2, PEX 7, and PEX27 genes. PEX gene function to transport phytanic acid to the peroxisomal compartment for breakdown is disrupted, leading to abnormal fat build-up in body tissues and blood plasma.
What Are the Signs and Symptoms of Refsum Disease?
Signs and symptoms related to Refsum disease are:
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Retinitis pigmentosa (damage to the retina -the back wall of the eye causing loss of night vision).
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Complete loss of vision in severe cases.
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Anosmia (loss of smell).
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Ichthyosis (dry, scaly, and thick skin).
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Weakness of muscles in upper and lower limbs (arms and legs).
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Loss of balance and coordination (due to Cerebral ataxia-Injury to the cerebellum area of the brain).
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Abnormal heart rate (in rare cases).
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Nystagmus (uncontrolled eye movements).
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Structural defects of hands and feet (bone defects leading to short hands or feet).
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Skeletal defects (affecting elbow, shoulder, and knee joints).
How Is Refsum Disease Diagnosed?
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History and Clinical Examination: The Diet history of the patient is noted. Clinical examination of eyes, hands, and feet is done to rule out any defects associated with Refsum disease.
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X-Ray of Hands and Feet: It is done to check the bone abnormalities in the hands and feet.
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Electrocardiogram (ECG): It is done to rule out any heart rate and rhythm abnormalities.
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Molecular Gene Test: Genetic testing is done to check for the presence of PHYH (Phytanoyl-CoA 2-Hydroxylase) and PEX7 (Peroxisomal Biogenesis Factor 7) gene mutation.
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Plasma Analysis: Blood plasma evaluation is done to check for the levels of phytanic acid in the body. Normally the blood plasma level of phytanic acid is less than 30 micromoles per liter, but it is raised to more than 200 micromoles per liter in the case of Refsum disease.
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Liver Biopsy: It is done to rule out abnormal functioning or the deficiency of enzyme phytanoyl-CoA Hydroxylase (PAHX) encoded by gene PHYH resulting in abnormal deposition of fats in the liver.
What Is the Treatment of Refsum Disease?
Treatment methods for Refsum disease are:
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Diet Restriction: Avoid food containing phytol like meats, fish, and dairy products (butter and cheese). The goal is to restrict the consumption of phytanic acid to less than ten milligrams to avoid abnormal build-up of fats in blood plasma and body tissues (liver and kidney).
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Therapeutic Plasma Exchange (TPE): It is done by plasmapheresis (method of removing blood plasma from the body) in cases where phytanic acid removal needs to be done rapidly. Therapeutic plasma exchange filters the phytanic acid out and reduces its concentration in the body. This helps to prevent the further progression of the disease. This method can control phytanic acid levels in the body for about sixty to seventy percent, which is around 100 micromoles per liter.
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Avoid Medications: Drugs like Ibuprofen and Amiodarone should be avoided as they can increase thyroxine levels. Both these drugs increase the level of phytic acid in the body and disrupt the metabolism of phytanic acid.
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Topical Drug Application: Dry, rough, and scaly skin can be treated with the application of skin creams and mineral oils.
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Genetic Counseling: Genetic counseling should be done for the patient and affected family members.
What Are the Complications That Can Occur if Refsum Disease Is Left Untreated?
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Heart Abnormalities: Like cardiomyopathy (inability of heart muscles to supply blood to the body effectively).
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Muscular Weakness: Weakness of the upper and lower limb muscles.
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Vision Abnormalities: Like blindness (complete loss of vision).
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Nerve Disorders: It occurs due to the deposition of phytanic acid on the myelin nerve sheath (outer covering of nerve) that causes a tingling sensation or tremor in the hands and feet.
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Brain Abnormalities: Like cerebellar ataxia (injury to the cerebellum area of the brain) resulting in loss of coordination and balance.
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Fatty Liver: It occurs due to abnormal deposition of fat in the liver because of disruption in fat breakdown.
Conclusion:
Refsum disease is a rare disorder affecting the breakdown of lipids (fat metabolism) which results in abnormal deposition of fats in the blood plasma and other body parts like the liver and kidney. It can affect both infants and teenagers, resulting in vision loss, loss of smell, muscle weakness, short limbs, and loss of balance which significantly affects the life of the patient. Early diagnosis of the condition is crucial to arrest the progression of the disease by reducing the amount of phytanic acid in the body by the treatment. Sometimes Refsum disorder is present since birth, but in some cases, signs and symptoms start appearing at ten to twenty years of age. Any signs and symptoms associated with the disease observed should be reported to the doctor immediately for early diagnosis and treatment.
