Feasibility of prenatal diagnosis of lysinuric protein intolerance by linkage analysis: A case report

Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of cationic amino acid transport (CAA), relatively common in Finland and Ital y. After weaning, LPI patients present poor feeding, vomiting and failure t o thrive. A severe pulmonary complication and episodes of metabolic imbalan ce may lead to death. Prenatal diagnosis has not been available due to lack of either biochemical or molecular markers to be used in the fetal period. The LPI locus has recently been assigned to chromosome 14q12, very close t o the T-cell receptor alpha-chain (TCRA) locus. We carried out a prenatal d iagnosis for LPI by linkage analysis in one LPI Italian family after CVS. F or the haplotype analysis 11 DNA markers from the LPI critical region were used (D14S742, D14S50, D14S283, five TCRA intragenic polymorphic sites, D14 S990, MYH7 and D14S80). It was concluded that the haplotype analysis indica ted that the fetus was healthy as he had inherited the two wild alleles of the LPI locus. After birth, the clearances of CAA were measured and found t o be in the normal range, thus confirming the result of the prenatal diagno sis. The prenatal diagnosis of LPI can now be offered to families affected by LPI. Copyright (C) 1999 John Wiley & Sons, Ltd.