HLA‐A,B,C,DR typing and 17‐OHP determination for second trimester prenatal diagnosis of 21‐hydroxylase deficient CAH

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Abstract
In 18 families at risk for the HLA‐linked, 21‐hydroxylase deficient form of autosomal recessive congenital adrenal hyperplasia (CAH), prenatal diagnosis (PD) was performed using two methods: (1) HLA‐A,B,C typing and in the latter 11 cases also DR typing of cultured amniotic fluid cells (AFC) using the standard microcytotoxicity assay, and (2) measurement of second trimester amniotic fluid 17‐hydroxyprogesterone (17‐OHP) concentration using gel chromatography and radioimmunoassay. The accuracy of the prenatal predictions was confirmed by postnatal HLA typing of umbilical cord blood lymphocytes and by clinical evaluation.In 16/18 families, both HLA typing of AFC and 17‐OHP measurements proved informative for PD. The predictions of both methods were concordant in 14/16 families (88 per cent). In ten of these families, a normal fetus was predicted, and in four, an affected fetus; all pregnancies were carried to term and all predictions were confirmed postnatally. In 2/16 cases (12 per cent), however, the predictions were discordant: the prenatal HLA typing indicated an affected fetus, whereas the 17‐OHP values predicted a normal fetus. Both pregnancies were continued and two healthy boys were delivered. The discordance proved to be due to a ‘missed’ HLA antigen in one case and to serologically cross‐reactive HLA antigens in the second.Finally, in 2/18 cases, prenatal assessment of fetal genotype had to rely on HLA typing alone as 17‐OHP measurement was not performed in one family and in the second family the 17‐OHP values obtained were not informative due to inadvertent continuation of hormone therapy to the date of amniocentesis. In both cases, the HLA typing data accurately predicted a normal fetus.In conclusion, a combination of HLA typing of cultured AFC and 17‐OHP measurements of amniotic fluid permits accurate prenatal diagnosis of CAH in most cases (88 per cent). In addition, the supplementary use of HLA‐DR typing of AFC as presented here for the first time proved helpful in families with HLA‐A.B homozygosity due to parental sharing of antigens and can be informative for identifying HLA‐B/21‐OH recombinant haplotypes.

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