ECE2019 Poster Presentations Adrenal and Neuroendocrine Tumours 1 (60 abstracts)
A novel CYP11B1 mutation presenting as a classical congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency
Isabel Mazarico 1 , Olga Giménez-Palop 1 , Lara Albert 1 , Luchtenberg Florencia 1 , Laia Casamitjana 1 , Ismael Capel 1 , David Subías 1 , Albert Cano 1 , Miriam Guitart 2 , Assumpta Caixàs 1 & Mercedes Rigla 1
1Endocrinology and Nutrition Department, Parc Taulí Hospital Universitari. Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain; 2Genetics Laboratory, UDIAT-Centre Diagnòstic, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain.
Background: Congenital adrenal hyperplasia (CAH) is a rare autosomal recessive disorder, of which 21-hydroxylase deficiency (21OHD) is the most frequent form. 11 beta-hydroxylase deficiency (11bOHD) is the second most common type of CAH. This pathology results from inactivating mutations in CYP11B1 gene.
Case presentation: We describe a case of a 48-year-old woman with 11bOHD, presented with hypokalemia hypertension, early adrenarche and mild virilization at age of 11 years. She was referred to our department at age of 46, after presenting an adrenal crisis, while suffering a pneumonia process, which was resolved with high dose corticoids. She had received over-replacement with glucocorticoids (hydrocortisone 40 mg/day) since she was 11 and developed long-term complications such as osteopenia and poorly controlled hypertension in spite of use of 4 drugs. Physical examination showed cushingoid appearance, with excessive hair growth, short adult stature (145 cm) and central obesity (BMI 38 kg/m2). She had neither obvious abnormalities in external genitalia at birth nor menstrual disorders. She presented mild left ventricular hypertrophy and hypertensive nephropathy as end-organ damage secondary to hypertension. The biochemical results of the diagnosis during childhood were not available and genetic study was not previously performed. Laboratory examination, under glucocorticoid treatment, revealed low ACTH levels, low androgen levels, normal serum aldosterone and rennin activity and high deoxycorticosterone (DOC) levels. A molecular analysis by sequencing CYP11B1 gene exome identified a homozygous splicing mutation, c.596-2A>G, not previously reported. This modification in the splice site consensus sequence affects the acceptor critical site in the intron 3- exon 4 boundary. The mutation will most likely lead to a loss of enzymatic activity. Therefore, we confirmed the diagnosis of CAH due to 11bOHD. Following the diagnosis, the patient was advised to reduce the dosage of hydrocortisone to 20 mg day (10 mg in the morning, 5 mg in midday and 5 mg in the afternoon). After dose adjustment of glucocorticoid, blood pressure improved, she lost weight and clinical parameters ameliorated. We did not prescribe treatment with spironolactone because she had high concentration of potassium and her hirsutism disappeared only with glucocorticoid treatment.
Conclusions: We have identified a novel mutation of CYP11B1 causing CAH. Recognition of novel mutations is clinically significant and would contribute to the knowledge of the phenotype-genotype relationship of CAH in the future.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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