Glycosylation defects underlying fetal alcohol spectrum disorder: a novel pathogenetic model. "When the wine goes in, strange things come out" - S.T. Coleridge, The Piccolomini.
J Inherit Metab Dis
; 35(3): 399-405, 2012 May.
Article
en En
| MEDLINE
| ID: mdl-22134542
Fetal alcohol spectrum disorder (FASD) is an umbrella term used to describe the craniofacial dysmorphic features, malformations, and disturbances in growth, neurodevelopment and behavior occurring in individuals prenatally exposed to alcohol. Fetal alcohol syndrome (FAS) represents the severe end of this spectrum. Many pathophysiological mechanisms have hitherto been proposed to account for the disrupted growth and morphogenesis seen in FAS. These include impaired cholesterol-modification of the Sonic hedgehog morphogen, retinoic acid deficiency, lipoperoxidative damage due to alcohol-induced reactive oxygen species combined with reduced antioxidant defences, and malfunctioning cell adhesion molecules. In this report, we propose a completely novel concept regarding the pathogenesis of FAS. Based on our observation that transferrin isoelectric focusing (TIEF) - the most widely used screening tool for congenital disorders of glycosylation (CDG) - was transiently abnormal in a newborn with FAS and a confirmed maternal history of gestational alcohol abuse, we came to believe that FAS exemplifies a congenital disorder of glycosylation secondary to alcohol-inflicted disruption of (N-linked) protein glycosylation. Various pieces of evidence were found in the literature to substantiate this hypothesis. This observation implies, among others, that one might need to consider the possibility of maternal alcohol consumption in newborns with transient glycosylation abnormalities. We also present an integrated pathophysiological model of FAS, which incorporates all existing theories mentioned above as well as our novel concept. This model highlights the pivotal role of disrupted isoprenoid metabolism in the origination of FAS.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Glicosilación
/
Trastornos del Espectro Alcohólico Fetal
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
/
Infant
/
Male
/
Newborn
/
Pregnancy
Idioma:
En
Revista:
J Inherit Metab Dis
Año:
2012
Tipo del documento:
Article
País de afiliación:
Países Bajos
Pais de publicación:
Estados Unidos