ESPE Abstracts (2014) 82 P-D-3-1-631

Homozygous c.923dupT Combined with Heterozygous c.334G[gt]A CYP21A2 Mutation: a Case Report from the Bulgarian CAH Screening Programme

Antoaneta Kostovaa, Iva Stoevaa, Andrey Kirovb,c, Ganka Dinevaa, Tihomir Todorovc, Albena Todorovab,c, Elissaveta Stefanovad, Krassimira Kazakovad, Ani Aroyoa & Vanio Mitevb


aUniversity Pediatric Hospital, ‘Screening and Functional Endocrine Diagnostics’, Medical University Sofia, Sofia, Bulgaria; bDepartment of Medical Chemistry and Biochemistry, Medical University Sofia, Sofia, Bulgaria; cGenetic Medico-Diagnostic Laboratory Genica, Sofia, Bulgaria; dUniversity Pediatric Hospital, Clinic of Pediatric Endocrinology and Genetics, Medical University Sofia, Sofia, Bulgaria


Background: This case underlines the importance of a newborn screening programme combined with genotyping for confirmation and prognosis of disease severity.

Objective and hypotheses: Case presentation of a girl with three CYP21A2 mutations.

Method: Girl, born from first uneventful pregnancy per vias naturalis. Birthweight 3200 g, birthlenght 50 cm. Intensive jaundice, start at d3, necessitating phototherapy. Discharged from the neonatal ward on the 7th day, clinically healthy, weight 2970 g. Breastfed. From the 9th day on begin to vomit a little after each feeding.

Results: 17-OH-progesterone from dried blood spot (taken on the 4th day) >285 (578.7) nmol/l. The excessively elevated 17-OH-progesterone was highly suspicious for CAH and necessitated immediate referral to the Screening Unit at the University Pediatric Hospital, Sofia. The evaluation at the 11th day revealed: delayed weight gain, jaundice, decreased skin elasticity, 2nd virilisation grade (Prader), hyperpigmented areoles and labia. Hyponatriemia (Na-129 mmol/l), hypokaliemia (K-8.1 mmol/l), a high hematocrit (64%), no metabolic acidosis, further increasing of 17-OHP levels (dried blood spot and serum), normal sized adrenals on ultrasound were evident. The girl was classified as salt wasting form of CAH and after informed consent blood for CYP21A2 molecular genetic studies of the family was drawn. Therapy started at day 11 (Urbason, Cortineff, iv rehydration); switch to oral hydrocortisone three times daily was performed later on with regular adaptations of the dosages according to 17-OHP profiles. Growth and development are according to that of healthy children, no new salt waste crisis occurred until 2 years of age. Sequencing of CYP21A2 revealed homozygous c.923dupT mutation and a heterozygous mutation c.334G>A.

Conclusion: The double mutated allele was inherited from the mother and it is most probably formed due to non-allelic homologous recombination between the CYP21A2 and its pseudogene. The c.923dupT mutation belongs to group Null CYP21A2 mutations.