Prenatal diagnosis of beta-thalassemia: 12 years' experience at a single laboratory in Pakistan

OBJECTIVE: To evaluate the service for prenatal diagnosis of beta-thalassemia in Pakistan. METHODS: All prenatal diagnoses (PNDs) for beta-thalassemia since the introduction of the service in 1994 were studied. PND was done by the Amplification Refractory Mutation System (ARMS), or linkage analysis, when required. The reported errors in PND were investigated for clerical mistakes, technical problems with PCR, maternal contamination and nonpaternity. RESULTS: In the 12 years 2174 PNDs were done for beta-thalassemia at the country's main referral center. The use of PND has increased from 26 in 1994 to 381 in 2006. Over 97% of the couples who requested PND already had an affected child. In over 97% of the cases PND was done by direct mutation analysis. The reported rate of misdiagnosis was 0.37%. The causes of misdiagnoses included one clerical mistake, three false positive PCR results, and two maternal contaminations in the chorionic villus sampling (CVS). CONCLUSION: PND for beta-thalassemia is technically feasible by direct mutation analysis in most cases in Pakistan. The procedure is quick and cost effective. Strict quality assurance can achieve an acceptably low error rate.