triolein and Zellweger-Syndrome

Clinically, peroxisome biogenesis disorders (PBDs) are a group of lethal diseases with a continuum of severity of clinical symptoms ranging from the most severe form, Zellweger syndrome, to the milder forms, infantile Refsum disease and rhizomelic chondrodysplasia punctata. PBDs are characterised by a number of biochemical abnormalities including impaired degradation of peroxide, very long chain fatty acids, pipecolic acid, phytanic acid and xenobiotics and impaired synthesis of plasmalogens, bile acids, cholesterol and docosahexaenoic acid. Treatment of PBD patients as a group is problematic since a number of patients, especially those with Zellweger syndrome, have significant neocortical alterations in the brain at birth so that full recovery would be impossible even with postnatal therapy. To date, treatment of PBD patients has generally involved only supportive care and symptomatic therapy. However, the fact that some of the milder PBD patients live into the second decade has prompted research into possible treatments for these patients. A number of experimental therapies have been evaluated to determine whether or not correction of biochemical abnormalities through dietary supplementation and/or modification is of clinical benefit to PBD patients. Another approach has been pharmacological induction of peroxisomes in PBD patients to improve overall peroxisomal biochemical function. Well known rodent peroxisomal proliferators were found not to induce human peroxisomes. Recently, our laboratory demonstrated that sodium 4-phenylbutyrate induces peroxisome proliferation and improves biochemical function (very long chain fatty acid beta-oxidation rates and very long chain fatty acid and plasmalogens levels) in fibroblast cell lines from patients with milder PBD phenotypes. Dietary supplementation and/or modification and pharmacological induction of peroxisomes as treatment strategies for PBD patients will be the subject of this review.

Topics: Antineoplastic Agents; Dietary Supplements; Drug Combinations; Erucic Acids; Humans; Peroxisomal Disorders; Phenylbutyrates; Triolein; Zellweger Syndrome

We investigated the possible therapeutic effect of decreasing plasma levels of very-long-chain fatty acids (C26:0) with a synthetic oil containing trioleate and trielucate (Lorenzo's oil) as well as increasing docosahexaenoic acid (DHA) in red blood cells (RBC) with DHA ethyl ester in four patients with Zellweger syndrome. We investigated serial changes of plasma C26:0 levels and DHA levels in RBC membranes by gas-liquid chromatography/mass spectrometry (GC/MS). After death, the fatty acid composition of each patient's cerebrum and liver was studied. Dietary administration of Lorenzo's oil diminished plasma C26:0 levels. Earlier administration of Lorenzo's oil was more effective and the response did not depend on the duration of administration. DHA was incorporated into RBC membrane lipids when administrated orally, and its level increased for several months. The final DHA level was correlated with the duration of administration and was not related to the timing of initiation of treatment. DHA levels in the brains and livers of treated patients were higher than in untreated patients. Early initiation of Lorenzo's oil and the long-term administration of DHA may be useful for patients with Zellweger syndrome.

Topics: Brain Chemistry; Docosahexaenoic Acids; Drug Combinations; Erucic Acids; Fatty Acids; Female; Humans; Infant; Liver; Male; Triolein; Zellweger Syndrome

We treated a girl with Zellweger syndrome using a special infant formula supplemented with middle chain triglyceride (MCT) milk, docosahexaenoic acid (DHA), Lorenzo's oil, and Lunaria oil, which is rich in nervonic acid (C24:1). We examined the fatty acid contents of the plasma and red blood cell (RBC) membrane. Neurological development was evaluated using Denver developmental screening test and auditory brainstem response (ABR). Her delayed neurological development, liver dysfunction, and cholestasis were all improved 2 weeks after starting the dietary treatment. DHA level in RBC membranes was increased and very long chain fatty acid (VLCFA,C26:0) levels were decreased. Our findings suggest that the dietary treatment with combination of MCT milk, DHA, Lorenzo's oil, and Lunaria oil in the patients with Zellweger syndrome bring some benefits for neurological development.

Topics: Child Development; Docosahexaenoic Acids; Drug Combinations; Drug Therapy, Combination; Erucic Acids; Evoked Potentials, Auditory, Brain Stem; Fatty Acids; Female; Humans; Infant, Newborn; Treatment Outcome; Triglycerides; Triolein; Zellweger Syndrome

Topics: Animals; Fatty Acids; Follow-Up Studies; Humans; Infant; Male; Milk; Triolein; Zellweger Syndrome