Aromatase Deficiency, a Rare Syndrome: Case Report

Abstract

Aromatase deficiency (AD) is a rare autosomal recessive inheritance syndrome. Its worldwide incidence is unknown, and there are few case reports in the literature. Aromatase dysfunction develops due to CYP19A1 gene mutation and a decrease in estrogen synthesis. Estrogen deficiency can induce delayed epiphyseal closure, eunuchoid body habitus, osteopenia, and osteoporosis in both genders. Our patient was a 27-year-old male who presented with bone pain, recurrent bone fractures associated with minimal trauma starting in puberty, and a progressive increase in height. Laboratory tests revealed that the blood levels of follicle-stimulating hormone and luteinizing hormone were above normal, testosterone level was normal, and estrogen was undetectable. Plain bone radiography of the left wrist and hand demonstrated that the epiphyses were still unfused. Lumbar osteoporosis was detected in bone densitometry. In the genetic analysis, homozygous R375H guanine-adenine (G-A) mutation was detected in the CYP19A1 gene, and a diagnosis of AD was reached. Treatment with 25 µg transdermal estradiol was started. All family members were examined. Homozygous R375H G-A mutation was detected in the patient’s younger brother. Heterozygous R375H G-A mutation was found in his mother, father, and older brother. In conclusion, this AD patient requires lifetime estrogen replacement in order to provide sufficient bone mineralization, to reduce the risk of bone fractures, and to lead a healthy life. The best method to prevent the possible complications is to diagnose the AD syndrome at early ages and to provide adequate estrogen replacement starting at puberty.Conflict of interest:None declared.

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

“…Metabolic syndrome-like phenotype has been described in adult male and female patients with aromatase deficiency. As shown in Table 2, we summarized a total of eight reported adult patients, including seven men and one woman (Baykan et al, 2013; Carani et al, 1997; Gagliardi et al, 2014; Herrmann et al, 2002; Lanfranco et al, 2008; Maffei et al, 2004, 2007; Morishima et al, 1995). The mean age is 27.6 years (range, 24–32).…”

MECHANISMS IN ENDOCRINOLOGY: Estradiol as a male hormone

“…In most cases, testicular size was normal (38,39,40,41,42,43,44,45), although a few men had low testicular volume (46,47,48,49), and cryptorchidism has been commonly reported (43,45,47,48). Where reported, sperm counts were normal (42,44) or reduced (39,46), commonly with altered sperm motility (44,46). A few men with aromatase deficiency have undergone testicular biopsy, showing varying degrees of impaired spermatogenesis including germ cell arrest (46,48,49).…”

“…Other human data support a role for E2 in limiting fat gain. Men with congenital aromatase deficiency are generally overweight or obese with excess abdominal adiposity (38,39,40,42,44,45,46,48,49). In one 9-month RCT randomizing abdominally obese men older than 40 years (n = 31) to transdermal DHT, transdermal testosterone or placebo, DHT treatment increased visceral adipose tissue (VAT) with no change in subcutaneous adipose tissue (SAT) or lean mass compared to testosterone-treated men (123).…”

Using three-point bending to evaluate tibia bone strength in ovariectomized young mice

“…Furthermore, individuals born with a deficiency of the cytochrome P450 gene for aromatase/estrogen synthase (CYP19 mutation), or estrogen insensitivity (estrogen receptor α gene mutation) lack the ability to produce adequate levels of estrogen or generate a normal in vivo response to estrogen, respectively [2,3]. The objective of this study is to determine how the depletion of gonadal estrogen affects bone strength in young females.…”