Endocrine Abstracts (2013) 32 P19 | DOI: 10.1530/endoabs.32.P19

Genetic analysis does not confirm NCCAH in almost half of the women who had received this diagnosis: preliminary results of an audit

Valeria Alcántara1, Diana Tundidor1, Susan Webb1,2, Gemma Carreras1, Juan Jose Espinos1, Ana Isabel Chico1, Silvia Martínez1, Francisco Blanco1 & Rosa Corcoy1

1Hospital de la Santa Creu I Sant Pau, Barcelona, Spain; 2CIBERER 747, Barcelona, Spain.

Introduction: Non-classical congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency is one of the most frequent autosomal recessive diseases. Genetic analysis performed for genetic counselling revealed a miscorrelation with the clinical diagnosis in several patients at our centre.

Aim: Confirm the genetic diagnosis of NCCAH in women attended for this condition.

Materials and methods: Consecutive patients attended at our centre are to be included. So far 26 patients have undergone medical record study collecting clinical, hormonal, and therapeutic information at diagnosis and follow-up into a standardized database. Analysis of the 21-hydroxylase gene has been performed through polymerase chain reaction, sequencing, and family genetic testing when possible.

Statistics: Descriptive analysis; data are expressed as percentages and medians(P25, P75).

Results: 84.6% of the patients were index cases. Age at first symptom was 16 years (9.23) and the number of symptoms was 2 (1–3). The most common manifestations were hirsutism (66.7%), oligomenorrhea (50.0%), infertility (15.4%), acne (11.5%), and alopecia (11.5%). At diagnosis, basal 17-hydroxyprogesterone(17OHP) was available in 73% of patients (21.6 nmol/l (6.97, 41)) and ACTH stimulation for 17OHP in 23% (141.9 (52, 175.2)). Genetic analysis revealed that 11.5% of the patients had no mutations, 30.8% were heterozygous for a single mild mutation, 30.7% homozygous for a mild mutation, and 26.9% compound heterozygotes for one mild and one severe mutation. The most common mutation was mild Val281Leu. Globally 42.3% of the patients’ genetic results did not confirm their clinical diagnosis.

Conclusion: In a substantial subset of patients in follow-up for NCCAH, hormonal work-up at diagnosis was inadequate. In almost half of the patients the genotype did not confirm the diagnosis. The diagnosis was confirmed in 81.3% of those with a sufficient hormonal diagnosis and in 20% of those with an insufficient one. These results compel us to reconsider the diagnostic and therapeutic requirements of these patients.