A novel compound heterozygous mutation of the aromatase gene in an adult man: reinforced evidence on the relationship between congenital oestrogen deficiency, adiposity and the metabolic syndrome.

[aromatase deficiency]

Descriptions of new cases of human aromatase deficiency are useful for a better understanding of male oestrogen pathophysiology , as some aspects remain controversial .To present a new case of an adult man affected by aromatase deficiency , along with a description of clinical phenotype , and hormonal and genetic analysis .Case report study .A 25 -year -old man with continuing linear growth , eunuchoid body habitus and diffuse bone pain .Amplification and sequencing of all coding exons with their flanking intronic sequences of the CYP 19 A 1 gene . Aromatase expression of the mutant human cDNAs was compared with wild type . Serum LH , FSH , testosterone , oestradiol , insulin , glucose , glycosylated haemoglobin (HbA 1 c ), serum lipids and liver enzymes were measured . Histological analysis of liver and testis biopsies was performed .Two novel heterozygous compound inactivating mutations of the CYP 19 A 1 gene were disclosed . The first mutation is at bp 380 (T -->G ) in exon IV and the second one at bp 1124 (G-->A ) in exon IX . LH and testosterone were normal , FSH was slightly elevated , and serum oestradiol undetectable . The subject showed a metabolic syndrome characterized by abdominal obesity , hyperinsulinaemia , acanthosis nigricans and nonalcoholic fatty liver disease .These novel mutations improve our knowledge on genetics of the CYP 19 A 1 gene . This new case of aromatase deficiency sheds new light on the heterogeneity of mutations in the CYP 19 A 1 gene causing loss of function of the aromatase enzyme . The evidence of metabolic syndrome and of obesity associated with congenital oestrogen deprivation emphasizes the role of oestrogens in fat accumulation and distribution in men , a role that has long been partially overlooked in these patients .

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aromatase deficiency

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