RESUMEN
Thirty years after the publication of Smith et al. [1964: J Pediatr 64:210-217] of 3(4) cases of the RSH/SLO ("Smith-Lemli-Opitz") syndrome and after the publication by Roux [1964: Arch Franç Pédiatr 21:451-464] on the teratogenic action of Triparanol, a defect of cholesterol metabolism was discovered by Tint and his co-workers in the blood of the patients of Irons and Elias [Irons et al., 1993: Lancet 341:1414]. In this manner, the RSH syndrome has been identified as another metabolic multiple congenital anomalies/mental retardation (MCA/MR) syndrome (prototype Zellweger syndrome) in which deficient cholesterol synthesis must be held responsible for all parts of the syndrome, including blastogenetic and organogenetic malformations, minor anomalies, more or less severe abnormalities of CNS and PNS structure and function, postnatal failure to thrive, and, in some cases, stillbirth or infancy/childhood death.
Asunto(s)
Anomalías Múltiples , Discapacidad Intelectual , Errores Innatos del Metabolismo Lipídico , Anomalías Múltiples/embriología , Anomalías Múltiples/genética , Anomalías Múltiples/metabolismo , Colesterol/biosíntesis , Mapeo Cromosómico , Cromosomas Humanos Par 7 , Cara/anomalías , Genitales/anomalías , Humanos , Discapacidad Intelectual/embriología , Discapacidad Intelectual/genética , Discapacidad Intelectual/metabolismo , Errores Innatos del Metabolismo Lipídico/embriología , Errores Innatos del Metabolismo Lipídico/genética , Microcefalia , Prevalencia , SíndromeRESUMEN
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common defect in fatty acid oxidation. The disease is inherited in an autosomal recessive fashion (carrier frequency around 1 in 70) and probably affects as many as 1 in 10000 new-borns. Affected children usually present within the two first years of life with recurrent episodes of hypoketotic hypoglycaemia and lethargy leading to death in approximately 25% of the cases. One mutation (c985A-->G) accounts for approximately 90% of the carrier chromosomes. We developed a preimplantation genetic diagnosis (PGD) strategy for MCAD for a couple who had already lost two affected children. When tested on heterozygous lymphoblasts, the amplification efficiency was 67 out of 71 (94%) and the allele drop-out rate was 0 out of 67. The patient became pregnant after one PGD cycle during which two embryos were replaced. The twin pregnancy was checked by chorionic villus sampling (CVS) and was shown to be unaffected. The twins have been born and are healthy.