Emerging Role for Tandem Mass Spectrometry in Detecting Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by a deficiency of one of five enzymes required for the synthesis of cortisol and aldosterone. The most common type of CAH is 21-hydroxylase deficiency (21OHD), which is attributable to mutations in the gene CYP21 and a pseudogene, CYP21P , located on the short arm of chromosome 6. As with other genetic disorders, genotype does not always predict phenotype. The phenotypic spectrum associated with 21OHD ranges from asymptomatic to early onset (as early as the fourth day of life) of severe salt-wasting crisis characterized by hypotension and electrolyte abnormalities that, if uncorrected, lead to death. Increased androgenic steroids, attributable to accumulated precursors proximal to the enzyme defect, cause ambiguous genitalia in female infants, leading to earlier clinical evaluation in girls. Virilized infant boys, however, are not always recognized, and many will present with acute catastrophic symptoms. Approximately 70% of infants with classic 21OHD have the salt-wasting form. All newborns in the US are offered medical screening that uses blood collected shortly after birth on filter-paper cards, but the disorders screened for vary from state to state. All US states screen for phenylketonuria (PKU) and congenital hypothyroidism, and 36 states screen for CAH (1). A filter-paper immunoassay to screen for CAH has been available since 1977 (2). This approach relies on measurement of 17-hydroxyprogesterone (17OHP), which is normally converted to 11-deoxycortisol by …