Glycerol trioleate/glycerol trierucate therapy in X-linked adrenoleukodystrophy: saturated and unsaturated fatty acids in blood cells. Implications for the follow-up.

Abstract

Adrenoleukodystrophy (X-ALD ; McKusick 300100) is an X-linked recessively inherited peroxisomal disorder, phenotypically heterogenous, characterized by progressive white-matter demyelination of the central nervous system and adrenocortical insufficiency. Biochemically, X-ALD is characterized by abnormal accumulation of saturated very long-chain fatty acids (VLCFA), particularly hexacosanoic acid (26 :0), owing to a deficiency of peroxisomal lignoceroyl-CoA synthetase activity. Some authors also suggest that fatty acid elongation activity plays an important role in the VLCFA accumulation (Koike et al 1991 ; Wilson et al 1992). It seems very likely that this accumulation is involved in the demyelinating process of the disease (Theda et al 1992). VLCFA are of dietary and endogenous origin (Moser et al 1992). Dietary restriction of VLCFA alone or together with oleic acid administration is not convincingly able to decrease 26 :0 levels in serum (Suzuki et al 1986 ; Rizzo et al 1987). The addition of erucic acid (22 :1) reduces VLCFA to control levels in the majority of patients (Rizzo et al 1989). Erucic acid, in contrast to oleic acid, is a minor component of dietary fatty acids, and can readily be increased by dietary supplementation. No serious side-effects have been reported with restriction of VLCFA and administration of glycerol trioleate and glycerol trierucate (GTO/GTE treatment), except thrombocytopenia observed in some patients (Aubourg et al 1993 ; Korenke et al 1995). Zierz and colleagues (1993) have demonstrated that thrombocytopenia is not due to reduced megakaryocytopoiesis. They have also found that when GTO/GTE treatment is replaced by GTO platelet counts return to normal ; because of this, they consider that thrombocytopenia is probably induced by GTE. Nevertheless, they cannot explain why only some, but not all, patients develop thrombocytopenia. Our earlier studies of VLCFA in mononuclear cells (MNC) in X-ALD showed that these blood cells are suitable for the establishment of homozygous and, especially, heterozygous status. Owing to the common origin of MNC and platelets, we suspected that MNC could provide more information about correlation between VLCFA and thrombocytopenia. In the present study, we have determined different VLCFA parameters in a group of 6 X-ALD patients on GTO/GTE treatment, in parallel in serum and MNC.