Treatment of an adrenomyeloneuropathy patient with Lorenzo's oil and supplementation with docosahexaenoic acid--a case report.

This is a case report of adrenomyeloneuropathy (AMN), the adult variant of adrenoleukodystryphy (ALD). The diagnoses in the patient, aged 34, was confirmed via increased serum very long chain fatty acid concentration (VLCFA). Treatment started with the cholesterol lowering drug, atorvastatin, followed by add-on therapy with Lorenzo's oil (LO) and finally supplementation with docosahexaenoic acid (DHA). The magnetic resonance imaging (MRI) scan of the AMN patient before DHA treatment, already showed abnormal white matter in the brain. Although the MRI showed no neurological improvement after 6 months of DHA treatment, no selective progression of demyelination was detected in the AMN patient. Contrary to what was expected, LO failed to sustain or normalize the VLCFA levels or improve clinical symptoms. It was however, shown that DHA supplementation in addition to LO, increased DHA levels in both plasma and red blood cells (RBC). Additionally, the study showed evidence that the elongase activity in the elongation of eicosapentaenoic acid (EPA) to docosapentaenoic acid (DPA) might have been significantly compromised, due to the increased DHA levels.

Early dietary treatments with Lorenzo's oil and docosahexaenoic acid for neurological development in a case with 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.

The X-linked adrenoleukodystrophy (X-ALD) and oxidative stress.

Most of the studies indicate that there is as yet no complete cure for X-ALD. However, methods of the treatment seem to slow rather than treat the disease. One method is the use of Lorenzo's oil in conjunction with a low fat diet, which may help in cerebral X-ALD. X-ALD is in very close resemblance to another neurodegenerative disease, amyotrophic lateral sclerosis (ALS). One of the believed pathomechanisms of ALS is oxidative stress; therefore, this article's emphasis on the role of reactive oxygen species in X-ALD. The aim of the present study was to review the literature concerning the advances in the treatment of X-adrenoleukodystrophy (X-ALD, OMIM # 300100) in the last two decades and to shed more light on the link between oxidative stress and X-ALD. This review article may point to a deficit in reactive oxygen species (ROS) scavenging and/or ROS overproduction being involved in the aetiopathology of these neurodegenerative diseases. Consequently, one of the useful neuronal rescue strategies could be the treatment with antioxidant agents.

[Diet therapy in the treatment of neuropediatric disorders]. / Dietas médicas en el tratamiento de las enfermedades neuropediátricas.

OBJECTIVES: This review focuses on the dietary treatment of four neuropediatric disorders: 1) X-linked adrenoleukodystrophy (X-ALD); 2) attention deficit disorders (ADD); 3) refractory epilepsy; and 4) inborn errors of metabolism. DEVELOPMENT: The use of Lorenzo's oil in the treatment of X-ALD has been controversial since no clear efficacy has been demonstrated because of a lack of controlled studies. Although this treatment normalizes the levels of very-long chain fatty acids in children with the cerebral form of X-ALD, the neurological symptoms persist or progress. The dietary treatment of ADD with or without hyperactivity consists of elimination diets such as the Feingold diet and megavitamins. Although the results of several controlled studies are contradictory, there is no scientific evidence that sugar, artificial food colorings or sweeteners are responsible for behavior or learning problems in children. The ketogenic diet has been effective for the control of refractory epilepsy such as infantile spasms and myoclonic seizures. Important side effects include gastrointestinal complaints, metabolic complications, poor growth and nutrition, liver abnormalities and renal calculi. The early identification and treatment of inborn errors of metabolism require prompt diagnosis and correction of metabolic abnormalities. Restriction of protein and fats may be necessary in certain neurometabolic disorders. A variety of special formulas is available to meet the nutritional requirements and avoid offending substances in neurometabolic patients. CONCLUSIONS: Dietary treatment plays an important role in the management of certain neuropediatric disorders, such as the use of special formulas in inborn errors of metabolism and the ketogenic diet in refractory epilepsy. The efficacy of Lorenzo's oil in the cerebral form of X-ALD and of the elimination of artificial food colorings and sweeteners in ADD remain to be proved.

Therapeutic developments in peroxisome biogenesis disorders.

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.

Plasma and red blood cell fatty acids in peroxisomal disorders.

The demonstration of abnormal levels of fatty acids or plasmalogens in plasma or red blood cells is key to the diagnosis of peroxisomal disorders. We report the levels of 62 fatty acids and plasmalogens in patients with X-linked adrenoleukodystrophy (X-ALD), Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD), both at baseline and after dietary interventions. "Lorenzo's Oil" therapy in X-ALD normalizes the levels of saturated very long chain fatty acids in plasma, but leads to reduced levels of omega 6 and other omega 3 fatty acids, and requires monitoring and appropriate dietary supplements. Patients with ZS, NALD and IRD have reduced levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) which can be normalized by the oral administration of microencapsulated DHA and AA.

Very long chain fatty acids in X-linked adrenoleukodystrophy brain after treatment with Lorenzo's oil.

The fatty acid composition of postmortem brain and liver from an adrenoleukodystrophy patient whose diet was supplemented with Lorenzo's oil (glycerol trioleate and glycerol trierucate) for 9 months was determined. The diet depressed plasma and liver saturated very long chain fatty acids (24:0 and 26:0) and increased plasma and liver erucic (22:1) and nervonic (24:1) acids. The levels of plasma linoleic (18:2 n-6), eicosopentaenoic (20:5 n-3), and docosahexaenoic (22:6 n-3) acids were also reduced, while the biochemical marker for essential fatty acid deficiency (20:3 n-9) was markedly increased in liver. However, we were unable to detect any corresponding changes in brain indicating that little erucic acid crossed the blood-brain barrier. Our findings suggest that dietary supplementation with Lorenzo's oil is of limited value in correcting the accumulation of saturated very long chain fatty acids in the brain of patients with adrenoleukodystrophy.