Spring 2008 Newsletter

CARES Foundation, Inc.

P450 Oxidoreductase Deficiency: Another Nonclassic CAH

A recently recognized abnormality in steroid biosynthesis, P450 oxidoreductase (POR) deficiency, is discussed in Genetic and Clinical Features of P450 Oxidoreductase Deficiency by Rachel R. Scott, MD &, Walter L. Miller, MD (Horm Res 2008; 69:266-275). This disorder is a distant relative of the much more common form of CAH, 21 hydroxylase (21OH) deficiency and is clinically far more devastating.

POR affects the production of a number of enzymes important for steroid synthesis (21 OH included) and results in a high serum concentration of 17-hydroxy progesterone, low serum androgen concentrations and poor cortisol response to ACTH stimulation. In addition, over 80% of the 50 recognized patients have skeletal abnormalities known as the Antley-Bixler Syndrome. The most serious of the bony abnormalities is coanal atresia a condition where the nasal passages are obstructed. This is serious for newborn babies because they will suffocate if they can’t breathe through the nose. Coanal atresia can prove fatal if not recognized and treated soon after birth. The remainder of the skeletal abnormalities are serious but not life-threatening and include midface hypoplasia, craniosynostosis, fusion of the radius and ulna, femoral bowing and femoral fractures. The manifestations of the abnormal steroid metabolism include female virilization (clitoromegaly and hypoplastic labia majora), male undervirilization (penile hypoplasia and crytorchidism), increased risk for adrenal crisis and, theoretically, abnormal drug metabolism by the liver.

Not everyone with Antley-Bixler Syndrome has POR. However, if a newborn baby has these skeletal abnormalities and a high serum 17-hydroxyprogesterone concentration on the newborn screening test, POR is a possible diagnosis. In addition, an older child with a number of skeletal problems fitting the Antley-Bixler Syndrome should be tested for POR.