Parental consanguinity: a probable cause for the high incidence of permanent neonatal hypothyroidism

To assess the relationship between parental consanguinity and permanent congenital hypothyroidism (PCH). From February 1998 to August 2002, cord dried blood spot samples, viz. only live births, in eight hospitals and a rural birth center in Tehran and Damavand were collected on Whatman BFC 180 filter papers. Samples with cord TSH  20 mU/L (two-site IRMA) were recalled. Between 7-14 days of life or thereafter, congenital hypothyroidism (CH) was confirmed by serum TSH > 10 mU/L and T4 < 6.5 g/dL and L-T4 was immediately started. CH-affected newborns were followed-up until May 2003. Thyroid dysgenesis was determined using 99m technetium pertechnetate thyroid scanning and/or ultrasonography. In thyroid eutopic newborns, dyshormonogenesis was diagnosed by a 4-week discontinuation of L-T4 between 2-3 years of age followed by abnormal serum TSH and T4 values. Of 35067 specimens, 373 (1.06%) were recalled, 25 had PCH (1:1403 births), 18 had thyroid dysgenesis (1:1948 births), and 7 had thyroid dyshormonogenesis (1:5010 births). Twenty-one PCH cases were detected from July 2000 onwards and 6648 (28.6%) of 23227 neonates had parental consanguinity. The odds ratio of parental consanguinity in PCH was 2.75 (95%CI: 1.17-6.47 P=0.02) and in dysgenesis was 3.74 (95%CI: 1.33-10.52 P=0.01) and the odds ratio of first-cousin parental consanguinity in PCH was 2.96 (95%CI: 1.23-7.15 P=0.02) and in dysgenesis was 3.21 (95%CI: 1.14-9.02 P=0.03) compared to non-PCH and non-dysgenetic cases, respectively. Parental consanguinity can be considered as the possible causative factor for the high prevalence of PCH and dysgenesis in Tehran.