Mucolipidosis III type C: first-trimester biochemical and molecular prenatal diagnosis

Objectives Mucolipidosis IIIC (MLIIIC) is a rare autosomal recessive lysosomal storage disease resulting from defective mannose 6‐phosphate‐dependent lysosomal enzyme trafficking; mutations of the γ subunit of N‐acetylglucosamine‐1 phosphotransferase (GINAcPT) were recently found to cause its pathogenesis. We report here for the first time prenatal diagnosis (PND) for MLIIIC by means of chorionic villous sampling (CVS). Methods and Results A fetus in a large Bedouin‐Moslem family was found to be homozygous for the founder haplotype and the mutational SSCP pattern of MLIIIC. The diagnosis was confirmed by markedly reduced lysosomal enzyme activities in cultured chorionic villi. The molecular identification of the disease‐causing mutation in this large Bedouin‐Moslem kindred permitted, for the first time, identification of carriers and couples at risk. Conclusions The feasibility of early PND for a progressive disabling disease is important for its prevention. Nevertheless, the feasibility of PND raises a serious dilemma since affected individuals might have a variable phenotype and the disease is progressive and non‐lethal. In addition, religious and social constraints are important factors to be taken into consideration in the genetic counseling of couples at risk. Copyright © 2003 John Wiley & Sons, Ltd.