Elevated Phytanic Acid: Causes, Genetic Factors, and Treatment Approaches

By SWA

This is a patient report VLCFAs test: 

Phytanic Acid:

  • Result: 2.46 µmol/L
  • Reference range: 0.25-2.07 µmol/L
  • Interpretation: High (H), elevated above the normal range.

    The lab report shows elevated phytanic acid levels, which might need further clinical evaluation. All other fatty acids tested are within the normal range, but it is noted that normal results don't completely rule out certain conditions such as X-ALD.

Phytanic acid is a branched-chain fatty acid primarily derived from the consumption of animal fats, dairy products, and fish. Elevated levels of phytanic acid, as seen with a 2.46 µmol/L result (above the reference range of 0.25-2.07 µmol/L), may indicate an underlying metabolic disorder or an issue with the body’s ability to break down this fatty acid. Genetic factors play a critical role in how the body processes phytanic acid, particularly in individuals with Refsum disease or related conditions.

Potential Causes of Elevated Phytanic Acid

1. Refsum Disease

One of the most common causes of elevated phytanic acid is Refsum disease, a rare inherited metabolic disorder. This condition is autosomal recessive, meaning that two copies of the defective gene must be inherited, one from each parent, for the disease to manifest.

In Refsum disease, there is a deficiency in the enzyme phytanoyl-CoA hydroxylase. This enzyme is essential for breaking down phytanic acid through a process called alpha-oxidation. Without this enzyme, phytanic acid accumulates in tissues and blood, leading to various symptoms such as:

  • Vision problems (retinitis pigmentosa),
  • Hearing loss,
  • Peripheral neuropathy (nerve damage),
  • Ataxia (loss of coordination).

Genetic Marker for Refsum Disease:

Refsum disease is associated with mutations in the PHYH gene or, in rarer cases, the PEX7 gene. These genes encode enzymes responsible for the breakdown of phytanic acid. Mutations in these genes result in enzyme deficiencies that prevent proper alpha-oxidation, causing phytanic acid accumulation. Genetic testing can identify these mutations, confirming a diagnosis of Refsum disease.

  • PHYH gene mutation: This is the primary gene associated with classical Refsum disease. Mutations in the PHYH gene disrupt the production of phytanoyl-CoA hydroxylase, the enzyme needed for alpha-oxidation.
  • PEX7 gene mutation: This gene is associated with a more generalized peroxisomal disorder but can also cause Refsum disease in rare cases.

2. Dietary Intake

In individuals without a genetic disorder, consuming a diet high in phytanic acid—such as one rich in dairy products, red meat, and certain fish—can result in elevated levels. However, this elevation is typically less severe compared to individuals with Refsum disease.

Role of Methylation in Phytanic Acid Metabolism

Methylation is a biochemical process that involves the addition of a methyl group to a molecule, which can affect gene expression and protein function. While methylation itself does not directly impact phytanic acid metabolism, disruptions in methylation pathways could theoretically influence gene expression in metabolic pathways. In general, methylation defects are not a primary factor in elevated phytanic acid levels but could have secondary effects in metabolic disorders.

Symptoms of Elevated Phytanic Acid

Elevated phytanic acid can lead to several neurological and systemic symptoms, which may vary in severity depending on the level of accumulation. Symptoms include:

  • Neurological issues such as muscle weakness, poor coordination, and nerve damage,
  • Vision impairments, such as night blindness or progressive vision loss,
  • Hearing impairments,
  • Thickened, scaly skin (ichthyosis),
  • Cardiac arrhythmias, which can be life-threatening if untreated.

Remedy and Management

1. Dietary Restrictions

The cornerstone of managing elevated phytanic acid is a low-phytanic acid diet. This involves restricting or eliminating foods high in phytanic acid:

  • Dairy products (milk, cheese, butter),
  • Fatty fish (cod, herring),
  • Ruminant fats (from beef, lamb, etc.).

A strict low-phytanic acid diet can effectively lower blood levels of phytanic acid and prevent symptoms in patients with Refsum disease.

2. Plasmapheresis

For individuals with severe elevations of phytanic acid, plasmapheresis may be necessary. This therapeutic procedure involves removing the plasma portion of the blood, where phytanic acid circulates, and replacing it with fluids or donor plasma to rapidly lower phytanic acid levels. Plasmapheresis is particularly useful in cases of acute toxicity or if dietary measures are not sufficient.

3. Regular Monitoring

Patients with elevated phytanic acid levels, particularly those diagnosed with Refsum disease, require regular monitoring to ensure that their phytanic acid levels remain controlled. Blood tests should be performed periodically, and dietary adjustments made as needed.

Pharmaceutical Treatments for Symptom Management

Although dietary management is the primary treatment, pharmaceutical interventions can help manage specific symptoms of elevated phytanic acid, particularly in individuals with Refsum disease.

a) Bile Acid Sequestrants (e.g., Cholestyramine, Colesevelam)

  • Use: These medications bind to bile acids in the intestine, preventing their reabsorption and promoting the excretion of lipophilic substances such as phytanic acid.
  • How It Helps: Bile acid sequestrants, such as cholestyramine or colesevelam, can be used to enhance the excretion of phytanic acid, reducing its levels in the body.

Examples:

b) Symptom-Specific Medications

In individuals with Refsum disease, medications may be used to manage specific symptoms:

  • Anti-seizure medications: For individuals experiencing seizures related to neurological damage.
  • Beta-blockers or anti-arrhythmics: To manage cardiac arrhythmias, which may occur in advanced cases of Refsum disease.

Examples:

Plasmapheresis (Non-Pharmaceutical Procedure)

Plasmapheresis is a treatment option that may be required when dietary control alone is insufficient to reduce phytanic acid levels. By removing plasma that contains phytanic acid and replacing it with plasma substitutes, plasmapheresis can quickly lower circulating phytanic acid levels and relieve acute symptoms.

Learn more about plasmapheresis: Plasmapheresis Overview - NCBI

Future Treatment: Gene Therapy

Gene therapy is an emerging treatment that may offer a more definitive solution for metabolic disorders like Refsum disease. By correcting the underlying genetic mutations (such as those in the PHYH or PEX7 genes), gene therapy could allow patients to metabolize phytanic acid normally, preventing its accumulation and associated symptoms. While not yet widely available, gene therapy holds promise for the future treatment of this rare condition.

Summary of Treatment Approach

  1. First line: Dietary restriction of phytanic acid.
  2. Pharmaceutical: Bile acid sequestrants (e.g., cholestyramine) to enhance phytanic acid excretion.
  3. Symptom management: Medications for specific symptoms such as seizures or cardiac arrhythmias.
  4. Severe cases: Plasmapheresis to rapidly lower phytanic acid levels.
  5. Future potential: Gene therapy to correct the underlying genetic cause of Refsum disease.

For further reading on Refsum disease and managing elevated phytanic acid, visit the Refsum Disease Foundation or consult a healthcare professional.

References:

  • NCBI: Phytanic Acid and Refsum Disease: Link to article
  • MedlinePlus Information: Cholestyramine Link

 

Note: Before starting any pharmaceutical treatment, it's essential to consult a healthcare provider to ensure appropriate management tailored to the individual’s condition.

Other VLCFs: 

  • Pristanic Acid:

  • C24:0 Tetracosanoic Acid:

  • C26:0 Hexacosanoic Acid:

  • Pristanic

  • C26:0 to C22:0 Ratio:

  • C22:0 Behenic Acid:

    • © 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right.
    Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9

     


     

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