Thrombocytopenia induced by erucic acid therapy in patients with X-linked adrenoleukodystrophy

Abstract

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 (84000-37000/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.

Hematological and lipid changes in newborn piglets fed milk‐replacer diets containing erucic acid

“…Bone marrow appeared to be normal on histological examination. This is in agreement with our previous piglet study (2) and in ALD patients (7,8). In addition, Zierz et al (7) reported that the bone marrow of ALD patients revealed no evidence of megakaryocyte reduction.…”

“…A similar thrombocytopenia was also observed in patients suffering from ALD, a sex-linked disorder in which very long-chain saturated fatty acids accumulate in all tissues, after treatment with "Lorenzo Oil," a 4:1 mixture of glycerol triolein and glycerol trierucin (6)(7)(8). The consumption of 22:1n-9 in these children was up to 18 g glycerol trierucin/d (7) or about 0.5 g 22:1n-9/kg body weight/day based on a body weight of 35 kg. Decreased platelet counts and increased size were directly attributed to dietary 22:1n-9, since its removal from the diet restored platelet numbers and size to normal (7).…”

“…A similar decrease in platelet counts was observed in patients suffering from X-linked adrenoleukodystrophy (ALD) who had received a dietary mixture of triolein and trierucin (4:1) in order to reduce their level of plasma very long chain saturated fatty acids, particularly 26:0 (6)(7)(8). These patients showed minor bruising, but no clinical symptoms of bleeding (6), and their platelet counts returned to normal after discontinuation of the diet (6,7). It is of interest to note that lower platelet counts are not limited to 22:1n-9 consumption.…”

“…The authors performed confirmatory studies to show that these platelet changes were not spuriously related to EDTA (8). ALD patients given a high triolein diet did not show symptoms of thrombocytopenia (7,8). There was no evidence of increased bleeding times in these patients, but a few patients showed a tendency to bruise easily (6).…”

“…The consumption of 22:1n-9 in these children was up to 18 g glycerol trierucin/d (7) or about 0.5 g 22:1n-9/kg body weight/day based on a body weight of 35 kg. Decreased platelet counts and increased size were directly attributed to dietary 22:1n-9, since its removal from the diet restored platelet numbers and size to normal (7). The authors performed confirmatory studies to show that these platelet changes were not spuriously related to EDTA (8).…”