Aromatase deficiency in a Chinese adult man caused by novel compound heterozygous CYP19A1 mutations: Effects of estrogen replacement therapy on the bone, lipid, liver and glucose metabolism.

[aromatase deficiency]

Aromatase deficiency is a rare disorder resulting in estrogen insufficiency in humans . It has been reported in remarkably few men with loss -of-function mutations in the CYP 19 A 1 gene encoding the aromatase , a cytochrome P 450 enzyme that plays a crucial role in the biosynthesis of estrogens from androgens . We investigated a non-consanguineous family including an adult man with clinical features of aromatase deficiency , and studied the effects of estrogen replacement in the man .We investigated the clinical and biochemical phenotype , performed CYP 19 A 1 mutational analysis in the family and 50 unrelated persons , studied the effects of CYP 19 A 1 mutations on aromatase protein structure , functionally characterized the mutations by cell-based aromatase activity assays , and studied the effects of estrogen replacement on the bone , lipid , liver and glucose metabolism .The man with clinical features of aromatase deficiency had novel compound heterozygous CYP 19 A 1 mutations (Y 81 C and L 451 P ) that were not found in 50 unrelated persons . Three -dimensional modeling predicted that Y 81 C and L 451 P mutants disrupted protein structure . Functional studies on the basis of in vitro expression showed that Y 81 C and L 45 P mutants significantly decreased the aromatase activity and catalytic efficiency . Estrogen replacement in the man increased bone mineral density , accelerated bone maturation , improved lipid profile and liver steatosis , and improved glucose levels but not insulin resistance .We have identified two novel CYP 19 A 1 missense mutations in an aromatase-deficient man . Estrogen replacement in the man shows great impact on recovering the impairments in the bone , lipid , liver and glucose metabolism , but fails to improve insulin resistance .

Diseases
Validation

Diseases presenting "mutations in the cyp19a1 gene" symptom

aromatase deficiency

You can validate or delete this automatically detected symptom