Prenatal diagnosis of X-linked adrenoleukodystrophy combining biochemical,immunocytochemical and DNA analyses

Amniocentesis was performed at 17 weeks' gestation on a 39-year-old woman a t risk of being a carrier for X-linked adrenoleukodystrophy (X-ALD). Her fi rst son had been affected with childhood cerebral X-ALD and had died at the age of nine years. DNA analysis had not been performed nor was any materia l available. The amniotic fluid cells (AFC) karyotype was found to be male and initial determination of very long chain fatty acids (VLCFA) in culture d amniocytes revealed borderline values. As an alternative strategy the com plete coding region of the ALD gene was amplified and sequenced using DNA i solated from both AFC and maternal leukocytes as templates. Sequencing of t he mother's DNA revealed the heterozygous pattern of a 2 bp deletion in exo n 5, the most frequent individual mutation leading to X-ALD. It has previou sly been described to result ina complete loss of protein. This deletion wa s excluded in the fetus. Accordingly, ALDP was readily detected in AFC by i mmunofluorescence. We conclude that under circumstances of incomplete data about the index case the combination of methods, namely DNA analysis of the heterozygous mother, and biochemical, immunocytochemical and DNA analyses in fetal cells can secure a reliable prenatal diagnosis of X-ALD. Copyright (C) 1999 John Wiley & Sons, Ltd.