X-linked adrenoleukodystrophy: first report of the Italian Study Group

Abstract

In this paper we report Italian data on X-linked adrenoleukodystrophy (ALD) collected from 1985 to 1997. This disease appears to be the most common of the peroxisomal disorders and is associated with a functional defect of the peroxisomal very long chain fatty acid (VLCFA) oxidation. In Italy 117 cases have been recognized, but many cases may be unrecognized due to the heterogeneous clinical manifestations that vary from mild to very severe forms. To control the devastating course of this disease two therapeutic approaches are under evaluation: bone marrow transplantation (BMT) and dietary treatment based on a mixture of glyceroyl trioleate (GTO) and glyceroyl trierucate (GTE). Our experience of 68 subjects submitted to dietary treatment shows that almost all patients with signs of cerebral involvement at the beginning of treatment worsened or died, patients with the milder form, adrenomyeloneuropathy (AMN), remained stable, while 4 of the 15 presymptomatic subjects developed neurological signs of the disease. In recent years a more accurate selection of patients and donors for BMT has given favourable results, but some strict criteria should be respected.

X-linked Adrenoleukodystrophy

“…The joint efforts of the laboratory of Hugo Moser and of Augusto Odone, a non-scientist father of a child (Lorenzo) suffering from X-ALD, gave rise to Lorenzo's oil treatment: administration of a 4:1 mixture of glyceryl trioleate and glyceryl trierucate associated with a moderate fat restriction [19]. The results of several uncontrolled studies converged towards the same conclusion: Lorenzo's oil does not halt the neurological progression in patients with ccALD, AMN or symptomatic women [399][400][401][402][403][404][405][406]. Concentration of C26:0 in plasma sphingomyelin and phosphatidylcholine were normalized by 4 months.…”

Adrenoleukodystrophy in Norway: High Rate of De Novo Mutations and Age-Dependent Penetrance

“…Therefore, both female and male subjects were included in this study. This is an important methodological difference between our Paper 1 and several of the previous studies [30,72,75,77,78], which look at males only (see Table 2, page 24). The most widely cited study, from the USA [76], used extrapolation of the results from the male population to estimate the frequency among females.…”

“…The prevalence of living X-ALD hemizygotes in the male population was 0.5:100,000. Several other studies [74,75,77,78] have used a method similar to the American, finding incidence figures of 1.6-3.6:100,000 (see Table 2, page 24). However, the epidemiological basis for these calculations is poorly defined.…”

“…As seen from the diagnostic criteria for X-ALD used in this thesis ( Table 2, page 24). Method 1, used in the widely cited American [76] and most other population surveys [74,75,77,78] [83]. However, this method is only now being implemented in some American states [84], and was not available to us (see section 1.4).…”

A mixture of oleic, erucic and conjugated linoleic acids modulates cerebrospinal fluid inflammatory markers and improve somatosensorial evoked potential in X‐linked adrenoleukodystrophy female carriers

“…The other component, erucic acid, aims at reducing the elongation of docosanoic (22:0) to 26:0, by interfering with microsomal elongases. However, while LO is very effective in decreasing plasma VLCFAs, it does not seem sufficient to prevent ALD (Di Biase et al 1998). The efficacy of treatment with LO is questionable, even when the treatment begins at disease onset.…”