PRENATAL-DIAGNOSIS OF MEDIUM-CHAIN ACYL-COA DEHYDROGENASE (MCAD) DEFICIENCY IN A FAMILY WITH A PREVIOUS FATAL CASE OF SUDDEN UNEXPECTED DEATH IN CHILDHOOD

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a potentially fatal inherited disease with a carrier frequency of approximately 1:1 00 in most Caucasian populations. The disease is implicated in sudden unexpected death in childhood. A prevalent disease-causing point mutat ion (A985G) in the MCAD gene has been characterized, thus rendering di agnosis easy in the majority of cases. Since the clinical spectrum of MCAD deficiency ranges from death in the first days of life to an asym ptomatic life, there are probably other genetic factors-in addition to MCAD mutations-involved in the expression of the disease. Thus, famil ies who have experienced the death of a child from MCAD deficiency mig ht have an increased risk of a seriously affected subsequent child. In such a family we have therefore performed a prenatal diagnosis on a c horionic villus sample by a highly specific and sensitive polymerase c hain reaction (PCR) assay for the G985 mutation. The analysis was posi tive and resulted in abortion. We verified the diagnosis by direct ana lysis on blood spots and other tissue material from the aborted fetus and from family members.