aromatase deficiency in a male patient - case report and review of the literature

What is aromatase enzyme?

Aromatase, or CYP19A1, is a type II cytochrome CYP450 enzyme that catalyzes the conversion of C19 androgens to C18 estrogens. Its crucial role in both female and male physiology has been deduced from human and animal studies using aromatase inhibitors, genetically altered mice, and patients with aromatase deficiency. The latter is an extremely rare disorder. Its diagnosis is particularly difficult in males, who go through puberty normally and therefore usually present as adults with elevated testosterone, bone abnormalities (e.g., delayed bone age and low bone mass), and metabolic syndrome. In this report, we describe a new case of a male patient with aromatase deficiency harboring a known mutation who presented with less severe clinical and biochemical features.

Where is aromatase located?

Aromatase, or CYP19A1, is a type II cytochrome P450 enzyme located in the endoplasmic reticulum [1]. It catalyzes the conversion of C19 steroids testosterone, 16alpha-hydroxytestosterone, and androstenedione to C18 steroids 17beta-estradiol, estriol, and estrone respectively [1]. The CYP19A1 gene is located on chromosome 15q21.2 and encodes a roughly 500 amino acid long protein that is expressed throughout the body, including the placenta, gonads, adipose tissue, bone, cartilage, skin, brain and vascular smooth muscle [1], [2]. The distinct phenotypes of patients with aromatase deficiency as well as aromatase knockout mice have confirmed a crucial role of aromatase in both female but also male physiology. While the first publications of aromatase expression and its regulation date back to the 1970s, the first case of a patient with aromatase deficiency was only reported in 1991 in a female infant who exhibited signs of a 46, XX disorder of sexual development. In addition, the patient's mother showed increased signs of virilization, elevated androgen levels, and low serum and urinary estrogen levels during the third trimester of her pregnancy [3].

What is the specific nature of mutation c.628G > A?

We conclude that the specific nature of mutation c.628G > A, which can potentially result in several different forms of the aromatase enzyme, may lend an explanation to the variable phenotypes associated with this particular genotype.

What is aromatase enzyme?

Aromatase, or CYP19A1, is a type II cytochrome CYP450 enzyme that catalyzes the conversion of C19 androgens to C18 estrogens. Its crucial role in both female and male physiology has been deduced from human and animal studies using aromatase inhibitors, genetically altered mice, and patients with aromatase deficiency. The latter is an extremely rare disorder. Its diagnosis is particularly difficult in males, who go through puberty normally and therefore usually present as adults with elevated testosterone, bone abnormalities (e.g., delayed bone age and low bone mass), and metabolic syndrome. In this report, we describe a new case of a male patient with aromatase deficiency harboring a known mutation who presented with less severe clinical and biochemical features.

What is the specific nature of mutation c.628G > A?

We conclude that the specific nature of mutation c.628G > A, which can potentially result in several different forms of the aromatase enzyme, may lend an explanation to the variable phenotypes associated with this particular genotype.