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 "bone mineral density" symptom

achondroplasia

adrenal incidentaloma

allergic bronchopulmonary aspergillosis

aromatase deficiency

congenital adrenal hyperplasia

cushing syndrome

dentinogenesis imperfecta

erythropoietic protoporphyria

fabry disease

familial hypocalciuric hypercalcemia

familial mediterranean fever

kallmann syndrome

lamellar ichthyosis

phenylketonuria

primary hyperoxaluria type 1

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