Genotype, Mortality, Morbidity, and Outcomes of 3β-Hydroxysteroid Dehydrogenase Deficiency in Algeria
Background3β-hydroxysteroid dehydrogenase 2 (3βHSD2) deficiency is a rare form of congenital adrenal hyperplasia (CAH), with fewer than 200 cases reported in the world literature and few data on outcomes.Patients and MethodsWe report a mixed longitudinal and cross-sectional study from a single Alger...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.867073/full |
| _version_ | 1811248167131283456 |
|---|---|
| author | Asmahane Ladjouze Malcolm Donaldson Ingrid Plotton Nacima Djenane Kahina Mohammedi Véronique Tardy-Guidollet Delphine Mallet Kamélia Boulesnane Zair Bouzerar Yves Morel Florence Roucher-Boulez |
| author_facet | Asmahane Ladjouze Malcolm Donaldson Ingrid Plotton Nacima Djenane Kahina Mohammedi Véronique Tardy-Guidollet Delphine Mallet Kamélia Boulesnane Zair Bouzerar Yves Morel Florence Roucher-Boulez |
| author_sort | Asmahane Ladjouze |
| collection | DOAJ |
| description | Background3β-hydroxysteroid dehydrogenase 2 (3βHSD2) deficiency is a rare form of congenital adrenal hyperplasia (CAH), with fewer than 200 cases reported in the world literature and few data on outcomes.Patients and MethodsWe report a mixed longitudinal and cross-sectional study from a single Algerian center between 2007 and 2021. Virilization and under-masculinization were assessed using Prader staging and the external masculinization score (EMS), pubertal development staged according to the system of Tanner. Adrenal steroids were measured using mass spectrophotometry (LC-MS/MS). A genetic analysis of HSD3B2 was performed using Sanger sequencing.ResultsA 3βHSD2 defect was confirmed in 6 males and 8 females from 10 families (8 consanguineous), with p.Pro222Gln mutation in all but two siblings with a novel deletion: c.453_464del or p.(Thr152_Pro155del). Probable 3βHSD2 deficiency was diagnosed retrospectively in a further 6 siblings who died, and in two patients from two other centers. In the genetically confirmed patients, the median (range) age at presentation was 20 (0–390) days, with salt-wasting (n = 14) and genital anomaly (n = 10). The Prader stage for female patients was 2 (1–2) with no posterior fusion of the labia. The EMS for males was 6 (3–9). Median (range) values at diagnosis for 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEA-S), and 17-hydroxypregnenolone (17OHPreg) were elevated: 73.7 (0.37–164.3) nmol/L; 501.2(9.4–5441.3) nmol/L, and 139.7 (10.9–1500) nmol/l (NB >90 nmol/L diagnostic of 3βHSD2 defect). Premature pubarche was observed in four patients (3F:1M). Six patients (5F:1M) entered puberty spontaneously, aged 11 (5–13) years in 5 girls and 11.5 years in one boy. Testicular adrenal rest tumors were found in three boys. Four girls reached menarche at 14.3 (11–14.5) years, with three developing adrenal masses (surgically excised in two) and polycystic ovary syndrome (PCOS), with radiological evidence of ovarian adrenal rest tumor in one. The median IQ was 90 (43–105), >100 in only two patients and <70 in three.ConclusionsThe prevalence of 3βHSD2 deficiency in Algeria appears high, with p.Pro222Gln being the most frequent mutation. Mortality is also high, with significant morbidity from adrenal tumors and PCOS in adolescence and an increased risk of learning disability. The finding of adrenal tumors in older patients with 3βHSD2 indicates under-replacement, requiring effective hydrocortisone and fludrocortisone treatment rather than surgical removal. |
| first_indexed | 2024-04-12T15:22:16Z |
| format | Article |
| id | doaj.art-f02b49e95a504f2db237a481c5202d46 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-12T15:22:16Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-f02b49e95a504f2db237a481c5202d462022-12-22T03:27:24ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-06-011310.3389/fendo.2022.867073867073Genotype, Mortality, Morbidity, and Outcomes of 3β-Hydroxysteroid Dehydrogenase Deficiency in AlgeriaAsmahane Ladjouze0Malcolm Donaldson1Ingrid Plotton2Nacima Djenane3Kahina Mohammedi4Véronique Tardy-Guidollet5Delphine Mallet6Kamélia Boulesnane7Zair Bouzerar8Yves Morel9Florence Roucher-Boulez10Department of Paediatrics, Centre Hospitalo-Universitaire Bab El Oued, Algiers, AlgeriaSection of Child Health, School of Medicine, Queen Elizabeth University Hospital, Glasgow, United KingdomMolecular Endocrinology and Rare Diseases, Hospices Civils de Lyon, Lyon University Hospital, Bron-Lyon, FranceDepartment of Pathological Anatomy, Centre Hospitalo-Universitaire Bab El Oued, Algiers, AlgeriaDepartment of Paediatrics, Centre Hospitalo-Universitaire Bab El Oued, Algiers, AlgeriaMolecular Endocrinology and Rare Diseases, Hospices Civils de Lyon, Lyon University Hospital, Bron-Lyon, FranceMolecular Endocrinology and Rare Diseases, Hospices Civils de Lyon, Lyon University Hospital, Bron-Lyon, FranceDepartment of Paediatrics, Centre Hospitalo-Universitaire Bab El Oued, Algiers, AlgeriaDepartment of Paediatrics, Centre Hospitalo-Universitaire Bab El Oued, Algiers, AlgeriaMolecular Endocrinology and Rare Diseases, Hospices Civils de Lyon, Lyon University Hospital, Bron-Lyon, FranceMolecular Endocrinology and Rare Diseases, Hospices Civils de Lyon, Lyon University Hospital, Bron-Lyon, FranceBackground3β-hydroxysteroid dehydrogenase 2 (3βHSD2) deficiency is a rare form of congenital adrenal hyperplasia (CAH), with fewer than 200 cases reported in the world literature and few data on outcomes.Patients and MethodsWe report a mixed longitudinal and cross-sectional study from a single Algerian center between 2007 and 2021. Virilization and under-masculinization were assessed using Prader staging and the external masculinization score (EMS), pubertal development staged according to the system of Tanner. Adrenal steroids were measured using mass spectrophotometry (LC-MS/MS). A genetic analysis of HSD3B2 was performed using Sanger sequencing.ResultsA 3βHSD2 defect was confirmed in 6 males and 8 females from 10 families (8 consanguineous), with p.Pro222Gln mutation in all but two siblings with a novel deletion: c.453_464del or p.(Thr152_Pro155del). Probable 3βHSD2 deficiency was diagnosed retrospectively in a further 6 siblings who died, and in two patients from two other centers. In the genetically confirmed patients, the median (range) age at presentation was 20 (0–390) days, with salt-wasting (n = 14) and genital anomaly (n = 10). The Prader stage for female patients was 2 (1–2) with no posterior fusion of the labia. The EMS for males was 6 (3–9). Median (range) values at diagnosis for 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEA-S), and 17-hydroxypregnenolone (17OHPreg) were elevated: 73.7 (0.37–164.3) nmol/L; 501.2(9.4–5441.3) nmol/L, and 139.7 (10.9–1500) nmol/l (NB >90 nmol/L diagnostic of 3βHSD2 defect). Premature pubarche was observed in four patients (3F:1M). Six patients (5F:1M) entered puberty spontaneously, aged 11 (5–13) years in 5 girls and 11.5 years in one boy. Testicular adrenal rest tumors were found in three boys. Four girls reached menarche at 14.3 (11–14.5) years, with three developing adrenal masses (surgically excised in two) and polycystic ovary syndrome (PCOS), with radiological evidence of ovarian adrenal rest tumor in one. The median IQ was 90 (43–105), >100 in only two patients and <70 in three.ConclusionsThe prevalence of 3βHSD2 deficiency in Algeria appears high, with p.Pro222Gln being the most frequent mutation. Mortality is also high, with significant morbidity from adrenal tumors and PCOS in adolescence and an increased risk of learning disability. The finding of adrenal tumors in older patients with 3βHSD2 indicates under-replacement, requiring effective hydrocortisone and fludrocortisone treatment rather than surgical removal.https://www.frontiersin.org/articles/10.3389/fendo.2022.867073/full3-β hydroxysteroid dehydrogenase deficiency3βHSD2HSD3B2congenital adrenal hyperplasianewborn screeningadrenal rest tumors |
| spellingShingle | Asmahane Ladjouze Malcolm Donaldson Ingrid Plotton Nacima Djenane Kahina Mohammedi Véronique Tardy-Guidollet Delphine Mallet Kamélia Boulesnane Zair Bouzerar Yves Morel Florence Roucher-Boulez Genotype, Mortality, Morbidity, and Outcomes of 3β-Hydroxysteroid Dehydrogenase Deficiency in Algeria Frontiers in Endocrinology 3-β hydroxysteroid dehydrogenase deficiency 3βHSD2 HSD3B2 congenital adrenal hyperplasia newborn screening adrenal rest tumors |
| title | Genotype, Mortality, Morbidity, and Outcomes of 3β-Hydroxysteroid Dehydrogenase Deficiency in Algeria |
| title_full | Genotype, Mortality, Morbidity, and Outcomes of 3β-Hydroxysteroid Dehydrogenase Deficiency in Algeria |
| title_fullStr | Genotype, Mortality, Morbidity, and Outcomes of 3β-Hydroxysteroid Dehydrogenase Deficiency in Algeria |
| title_full_unstemmed | Genotype, Mortality, Morbidity, and Outcomes of 3β-Hydroxysteroid Dehydrogenase Deficiency in Algeria |
| title_short | Genotype, Mortality, Morbidity, and Outcomes of 3β-Hydroxysteroid Dehydrogenase Deficiency in Algeria |
| title_sort | genotype mortality morbidity and outcomes of 3β hydroxysteroid dehydrogenase deficiency in algeria |
| topic | 3-β hydroxysteroid dehydrogenase deficiency 3βHSD2 HSD3B2 congenital adrenal hyperplasia newborn screening adrenal rest tumors |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.867073/full |
| work_keys_str_mv | AT asmahaneladjouze genotypemortalitymorbidityandoutcomesof3bhydroxysteroiddehydrogenasedeficiencyinalgeria AT malcolmdonaldson genotypemortalitymorbidityandoutcomesof3bhydroxysteroiddehydrogenasedeficiencyinalgeria AT ingridplotton genotypemortalitymorbidityandoutcomesof3bhydroxysteroiddehydrogenasedeficiencyinalgeria AT nacimadjenane genotypemortalitymorbidityandoutcomesof3bhydroxysteroiddehydrogenasedeficiencyinalgeria AT kahinamohammedi genotypemortalitymorbidityandoutcomesof3bhydroxysteroiddehydrogenasedeficiencyinalgeria AT veroniquetardyguidollet genotypemortalitymorbidityandoutcomesof3bhydroxysteroiddehydrogenasedeficiencyinalgeria AT delphinemallet genotypemortalitymorbidityandoutcomesof3bhydroxysteroiddehydrogenasedeficiencyinalgeria AT kameliaboulesnane genotypemortalitymorbidityandoutcomesof3bhydroxysteroiddehydrogenasedeficiencyinalgeria AT zairbouzerar genotypemortalitymorbidityandoutcomesof3bhydroxysteroiddehydrogenasedeficiencyinalgeria AT yvesmorel genotypemortalitymorbidityandoutcomesof3bhydroxysteroiddehydrogenasedeficiencyinalgeria AT florenceroucherboulez genotypemortalitymorbidityandoutcomesof3bhydroxysteroiddehydrogenasedeficiencyinalgeria |