Therapeutic effects of docosahexaenoic acid ethyl ester in patients with generalized peroxisomal disorders

M Martínez1, E Vázquez, M T García-Silva

  • 1Hospital Materno-Infantil Vall d'Hebron, Barcelona, Spain, and the Hospital 12 de Octubre, Madrid, Spain. mmartinez@cinet.fcr.es

Insights

Generalized peroxisomal disorders cause severe developmental issues due to low docosahexaenoic acid (DHA). DHA ethyl ester supplementation improved clinical symptoms, vision, and myelination in affected patients.

Area of Science:

  • Biochemistry
  • Neurology
  • Genetics

Background:

  • Generalized peroxisomal disorders are severe congenital diseases impacting the central nervous system, liver, and eyes, often leading to early mortality.
  • These disorders are characterized by impaired peroxisome formation and enzyme deficiencies, affecting plasmalogen synthesis and very-long-chain fatty acid (VLCFA) beta-oxidation.
  • Patients exhibit profound docosahexaenoic acid (DHA) deficiency in the brain, tissues, and blood, crucial for neuronal and retinal membrane function.

Purpose of the Study:

  • To investigate the therapeutic potential of normalizing docosahexaenoic acid (DHA) concentrations in patients with generalized peroxisomal disorders.
  • To assess the clinical efficacy and biochemical impact of DHA ethyl ester (DHA-EE) supplementation.

Main Methods:

  • Oral administration of purified DHA ethyl ester (DHA-EE) at daily doses of 100-500 mg to 13 patients.
  • Monitoring of DHA levels, plasmalogen concentrations, VLCFA levels, liver enzymes, and clinical parameters including vision, liver function, muscle tone, and social contact.
  • Magnetic resonance imaging (MRI) was used to evaluate brain myelination in some patients.

Main Results:

  • DHA-EE supplementation rapidly normalized blood DHA values within weeks.
  • Increased erythrocyte plasmalogen concentrations were observed in most patients.
  • Decreased plasma VLCFA levels and near-normalization of liver enzymes were noted.
  • Clinical improvements included enhanced vision, liver function, muscle tone, and social interaction.
  • MRI revealed normalization or improvement of brain myelination in several patients.

Conclusions:

  • The profound DHA deficiency is a key factor in the pathogenesis of generalized peroxisomal disorders, including Zellweger syndrome.
  • DHA ethyl ester (DHA-EE) therapy is a promising treatment, alleviating symptoms and improving outcomes in affected individuals.
  • Further research is warranted to fully elucidate the role of DHA in health and disease, supporting its therapeutic recommendation.

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