ESPE2023 Poster Category 1 Adrenals and HPA Axis (40 abstracts)
Congenital adrenal hyperplasia due to 11 β-hydroxylase deficiency: Clinical, Biochemical and Genetic characteristics
Asmahane Ladjouze 1,2 , kahina Mohammedi 3,2 , Mohamed Demdoum 4 , Kamelia Boulesnane 1,2 , Rawda Aboura 1,2 , Souhila Melzi 1,2 , Nadjet Bouhafs 1,2 , Malcolm Donaldson 5 , Clément Janot 6 , Delphine Mallet 6 , Zair Bouzerar 1,2 & Florence Roucher-Boulez 6
1Service de Pédiatrie, CHU Bab EL Oued, Algiers, Algeria. 2Faculté de Médecine d'Alger, Algiers, Algeria. 3Service de Pédiatrie, EPH Ain Taya, Algiers, Algeria. 4Cabinet Libéral, El Oued, Algeria. 53 Section of Child Health, School of Medicine, Queen Elizabeth University Hospital, Glasgow, United Kingdom. 6Molecular endocrinology and rare diseases, Hospices Civils de Lyon, Université Lyon1, Lyon, France
Background: Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1 (gene encoding 11β-hydroxylase), is a rare autosomal recessive disorder due to an impairment of the last steroidogenesis step. Consequences are a decreased cortisol secretion, elevated plasma levels of ACTH, and accumulation of steroid precursors responsible of hyperandrogenism and hypertension. It is the second most frequent cause of CAH after 21-Hydroxylase deficiency. Its incidence is estimated at 1:100 000 live births in non-consanguineous populations but may be as high as 1: 5000 in some specific populations.
Study aim: To estimate the prevalence, clinical and hormonal features, genetic findings and outcomes of patients with 11β-hydroxylase deficiency (11β-OHD) in our population.
Methods: Clinical and hormonal data were collected from the medical records of patients attending two centers in Algeria between 2007 and 2023. Genetic analysis of CYP11B1 was performed using Sanger sequencing after obtaining written informed consent from patients and parents.
Results: From a cohort of 290 patients with classic CAH, 11β-OHD was confirmed in 29 (10%) patients from 18 families with a high level of consanguinity (82.75%), M:F ratio 1:1.23. Molecular studies revealed different mutations in CYP11B1. The most frequent mutations in our population were: mutation c.650delinsTT (p.(Ser271Ilefs*42)) (3 families, 8 patients). c.1136G>T (1 family, 3 patients) and c.1066c>T (p.Gln356*) (3 families). One patient had a short intragenic inversion in CYP11B1. Age at diagnosis ranged from 20 days to 13 years. Male patients were diagnosed later than female patients (Mean age in boys 40.5 +/- 46 Months vs 16.7 +/-21.4 Months in girls). All males presented with pseudo-precocious puberty while females presented with virilization (Prader score 3-5), leading to wrong sex assignment at birth in 5 patients. Sex reassignment was refused by the parents of three patients. Hypertension was observed in 13 patients at a median age 4 years ([1.5-13.8 years]. One of the males presented TART (Age 9 years). Biochemistry showed mildly elevated 17OHprogesterone (Mean 43.81 nmol/l+/-39.35) and Δ4-androstenedione (mean 9.66 nmol/l +/-10.76; while 11-deoxycortisol was very high when measured (n=20: Mean 234 nmol/l+/- 150.27)
Conclusion: 11β-OHD appears more frequent in Algeria than reported elsewhere. The spectrum of genetic mutations is wider than in 3βHSD, c.650 delG insTT being the most common mutation. With late diagnosis, patient outcomes show a high prevalence of hypertension. Since 11β-OHD cannot be detected on CAH screening, timely diagnosis relies on careful neonatal examination, and early detection of advanced growth and sexual development.
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