Congenital adrenal hyperplasia (CAH) comprises a group of inherited autosomal recessive disorders characterised by defective
cortisol biosynthesis, compensatory increases in
corticotrophin secretion and adrenocortical
hyperplasia. The characteristics of the biochemical and clinical phenotype depend on the specific enzymatic defect.
21-hydroxylase deficiency is estimated to account for 90%-95% of all CAH cases. Although there are many variants of CAH, a new variant is found secondary to a mutation in the gene encoding the
protein P450
oxidoreductase (POR) in which the electron is granted to all microsomal
P450 enzymes type II. In 2004, it was discovered that this new CAH disease was attributable to the POR gene mutation. POR facilitates electron transfer from
Nicotinamide adenine dinucleotide phosphate (
NADPH) to key
enzymes involved in
steroid and
sterol synthesis and metabolism.
POR deficiency causes partial and combined impairment of the key
enzymes involved in steroidogenesis: P450c17 (17α-
hydroxylase/
17,20 lyase), P450c21 (21-hydroxylase) and P450aro (
aromatase). Clinically, mutant POR manifests with disordered sex development,
adrenal insufficiency and skeletal malformations. However, each
enzyme may be differently compromised in the same patient. This difference in the clinical manifestations secondary to the variability in enzymatic impairments ranges from
ambiguous genitalia in both sexes,
adrenal insufficiency associated or not to bone malformations, to abnormal laboratory results in the neonatal screening test of asymptomatic newborns. We report here a case of a 46, XY patient with normal male genitalia associated with
hypertension not related to
fludrocortisone in which genetic study showed that a homozygous mutation in the CYP21A2 also carries the heterozygous missense variant of unclear pathogenicity in the POR gene.Although there are many variants of CAH, a new variant is found secondary to a mutation in the gene encoding the
protein P450
oxidoreductase (POR) which therefore the electron is granted to all microsomal
P450 enzymes type II. In 2004, it was mentioned by Fluck and his colleagues that this new CAH disease was attributable to the POR gene mutation.POR facilitates electron transfer from
NADPH to key
enzymes involved in
steroid and
sterol synthesis and metabolism.
POR deficiency causes partial and combined impairment of the key
enzymes involved in steroidogenesis: P450c17 (17α-
hydroxylase/
17,20 lyase), P450c21 (21-hydroxylase) and P450aro (
aromatase).Clinically, Mutant POR manifests with disordered sex development,
adrenal insufficiency and skeletal malformations.However, each
enzyme may be differently compromised in the same patient. This difference in the clinical manifestations secondary to the variability in enzymatic impairments, it is ranging from
ambiguous genitalia in both sexes,
adrenal insufficiency associated or not to bone malformations, to abnormal laboratory results in the neonatal screening test of asymptomatic newborns.