دانلود رایگان مقاله کمبود آروماتاز در یک بیمار مرد

Abstract

Objective: 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 de- ficiency. 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. Case report: The patient presented with low bone mass and delayed bone age after a finger fracture at age 25 years. FSH, LH and testosterone levels were normal, but estradiol and estrone levels were absent or barely detectable, raising suspicion for aromatase deficiency. A homozygous c.628GNA mutation in exon 5 was confirmed by direct sequencing. Unlike previously reported cases of aromatase deficiency, he did not display biochemical features of insulin resistance, dyslipidemia, or overweight/obese status. Therapy with estradiol led to the closure of growth plates and a dramatic increase in bone mass. Conclusions: Here we explore genotype/phenotype associations of this new case compared to cases reported previously. We conclude that the specific nature of mutation c.628GNA, 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.

4. Discussion

During the last two decades, we have learned a great deal about the complex role of estrogen in both male and female physiology. Studies of patients with monogenic diseases and genetically altered mice are particularly valuable to further our understanding of estrogen actions. That said, aromatase, or in other words estrogen, deficiency, especially in males, is an extremely rare condition with 10 male cases reported so far [8–13,18–21]. With such a rare disease, the detailed description of each new case within the context of the available literature is therefore a valuable resource.