The Turkish Journal of Pediatrics
2012 , Vol 54 , Num 4
Association between genotype, clinical presentation, and severity of congenital adrenal hyperplasia: a review
1Department of Pediatrics, King Abdul-Aziz University Hospital, Faculty of Medicine, Jeddah and 2 Department of Internal
Medicine, North West Armed Forces Hospital, Tabuk, Kingdom of Saudi Arabia. E-mail: aagha@kau.edu.sa
Congenital adrenal hyperplasia (CAH) applies to a family of inherited disorders
of steroidogenesis caused by an abnormality in one of the five enzymatic steps
necessary in the conversion of cholesterol to cortisol. The enzyme defects are
transmitted as an autosomal recessive trait. Patients with a “classical” form
of CAH usually present during the neonatal and early infancy period with
adrenal insufficiency, which could be associated with a salt- losing pathology.
Females usually have genital ambiguity. Approximately 67% of classical CAH
patients are classified as “salt-losing”, while 33% have “non-salt-losing” or
the “simple-virilizing” form, reflecting the degree of aldosterone deficiency.
Non-classic 21-hydroxylase deficiency (NC 21-OHD) refers to the condition
in which partial deficiencies of 21-hydroxylation produce less extreme
hyperandrogenemia and milder symptoms. Females do not demonstrate genital
ambiguity at birth. The gene for adrenal 21-hydroxylase, CYP21, is located on
chromosome 6p in the area of human leukocyte antigen (HLA) genes. Specific
mutations may be associated with a certain degree of enzymatic compromise
and the clinical form of 21-hydroxylase deficiency (21-OHD). NC 21-OHD
patients are predicted to have mild mutations on both alleles and one severe
or one mild mutation of the 21-OH locus (compound heterozygote). This
review aims to describe the association between the genotype and clinical
presentations and severity of CAH.
Keywords :
congenital adrenal hyperplasia, adrenal insufficiency, genital ambiguity,
genetic mutation.