Abstract
BackgroundCerebrotendinous xanthomatosis (CTX) and Lathosterolosis represent two treatable inherited disorders of cholesterol metabolism that are characterized by the accumulation of cholestanol and lathosterol, respectively. The age of the patients suspected of having these disorders is highly variable due to the very different phenotypes. The early diagnosis of these disorders is important because specific therapeutic treatment could prevent the disease progression. The biochemical diagnosis of these defects is generally performed analyzing the sterol profile.Since age-related levels of these sterols are lacking, this study aims to determine a preliminary comparison of plasma levels of cholestanol and lathosterol among Italian unaffected newborns, children and healthy adults.MethodsThe sterols were extracted from 130 plasma samples (24 newborns, 33 children and 73 adults) by a liquid-liquid separation method and quantified by gas chromatography coupled with a flame ionization detector.ResultsCholesterol, cholestanol and lathosterol levels together with the cholestanol/cholesterol and lathosterol/cholesterol ratios are statistically different among the three groups. Cholesterol levels progressively increased from newborns to children and to adults, whereas cholestanol/cholesterol and cholestanol/lathosterol ratios progressively decreased from newborns to children and to adults. Lathosterol levels were higher in adults than in both newborns and children. In the total population a positive correlation was observed between cholesterol levels and both cholestanol (correlation coefficient = 0.290, p = 0.001) and lathosterol levels (correlation coefficient = 0.353, p < 0.0001).ConclusionsAlthough this study can only be considered an explorative experience due to the low number of analyzed samples, we revealed several differences of plasma cholestanol and lathosterol levels and their ratios to cholesterol levels among newborns, children and adults. These evidences indicate the need of age-related reference values of cholestanol and lathosterol concentrations, including also newborns and children.
Highlights
The inherited metabolic disorders of cholesterol synthesis and catabolism are characterized by an overall breadth and diversity of clinical features including major somatic and/or CNS malformations and dysmorphic features [1]
An overall difference of cholestanol levels was observed among the groups (p = 0.024), differences were not observed by multiple comparisons (Fig. 1b)
We found that the plasma levels of lathosterol, a surrogate marker of cholesterol biosynthesis [27], were significantly lower in newborn and children than adults, whereas no differences are observed between newborns and children
Summary
The inherited metabolic disorders of cholesterol synthesis and catabolism are characterized by an overall breadth and diversity of clinical features including major somatic and/or CNS malformations and dysmorphic features [1]. These disorders show overlapping phenotypes, they are characterized by the accumulation of specific non–cholesterol sterols in blood and tissues of affected patients [2, 3]. Cerebrotendinous xanthomatosis (CTX) and Lathosterolosis represent two treatable inherited disorders of cholesterol metabolism that are characterized by the accumulation of cholestanol and lathosterol, respectively. Since age-related levels of these sterols are lacking, this study aims to determine a preliminary comparison of plasma levels of cholestanol and lathosterol among Italian unaffected newborns, children and healthy adults
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