trierucate and Adrenoleukodystrophy

Topics: Adrenoleukodystrophy; Erucic Acids; Fatty Acids; Fatty Acids, Unsaturated; Genetic Linkage; Humans; Leukocytes, Mononuclear; Triglycerides; Triolein; X Chromosome

We have investigated the effect of glyceroltrioleate/glyceroltrierucate (GTO/GTE) therapy on X-chromosomal adrenoleukodystrophy in 16 patients with adrenoleukodystrophy (n = 6), adrenomyeloneuropathy (n = 3), Addison disease without neurological involvement (n = 2), and neurologically and endocrinologically asymptomatic patients (n = 5). Therapy was carried out for 19.4 +/- 10 months. All patients showed a normalization of C 26:0 plasma fatty acid concentrations. None of the seven neurologically asymptomatic patients developed neurological symptoms. Somatosensory evoked potentials of the tibialis nerve was the most sensitive electrophysiological parameter, showing a slight improvement in neurologically asymptomatic patients during therapy. In none of the patients with normal cranial MRI at start of therapy (n = 6) has MRI deterioration been observed whilst on therapy. Follow up of the neurologically asymptomatic children supports the hypothesis that GTO/GTE therapy might prevent the development of neurological symptoms. Six of the nine neurologically symptomatic patients deteriorated to varying degrees whilst on therapy. MRI alterations have worsened in all patients with clinical deterioration.. GTO/GTE treatment should be initiated in all neurological asymptomatic boys before first neurological symptoms develop. To discover these patients very long-chain fatty acid determination should be performed in all family members at risk when adrenoleukodystrophy or adrenomyeloneuropathy is diagnosed.

Topics: Adolescent; Adrenal Cortex Function Tests; Adrenoleukodystrophy; Adult; Age of Onset; Child; Child, Preschool; Demyelinating Diseases; Erucic Acids; Evoked Potentials, Somatosensory; Fatty Acids; Humans; Leukopenia; Magnetic Resonance Imaging; Male; Middle Aged; Neural Conduction; Spinal Nerves; Thrombocytopenia; Triglycerides; Triolein; X Chromosome

Five patients with various clinical and genetic phenotypes of adrenoleukodystrophy were treated with a diet enriched with glycerol trioleate and glycerol trierucate (GTE). In all patients platelet counts decreased upon the administration of GTE, but no bleeding symptoms occurred in any of the patients, and bleeding time remained normal. Pseudothrombocytopenia was excluded in all patients. Thrombocytopenia was marked (84,000-37,000/mm) in three of the patients but was fully reversible after discontinuation of GTE. Mean platelet volumes were abnormally increased in all patients. When GTE was again administered by stepwise increasing the daily dose, platelet counts showed a clearly dose-dependent decrease. Bone marrow biopsies revealed no evidence of reduced megakaryocytopoiesis. The data indicate that in patients with adrenoleukodystrophy treated with GTE platelet counts should be closely monitored because thrombocytopenia may limit the maximal daily intake of GTE.

Topics: Adrenoleukodystrophy; Adult; Dose-Response Relationship, Drug; Drug Therapy, Combination; Erucic Acids; Female; Genetic Linkage; Humans; Male; Middle Aged; Platelet Count; Thrombocytopenia; Triglycerides; Triolein; X Chromosome