Additional evidence for the role of chromosomal imbalances and SOX8, ZNRF3 and HHAT gene variants in early human testis development.

BACKGROUND: Forty-six ,XY Differences/Disorders of Sex Development (DSD) are characterized by a broad phenotypic spectrum ranging from typical female to male with undervirilized external genitalia, or more rarely testicular regression with a typical male phenotype. Despite progress in the genetic diagnosis of DSD, most 46,XY DSD cases remain idiopathic. METHODS: To determine the genetic causes of 46,XY DSD, we studied 165 patients of Tunisian ancestry, who presented a wide range of DSD phenotypes. Karyotyping, candidate gene sequencing, and whole-exome sequencing (WES) were performed. RESULTS: Cytogenetic abnormalities, including a high frequency of sex chromosomal anomalies (85.4%), explained the phenotype in 30.9% (51/165) of the cohort. Sanger sequencing of candidate genes identified a novel pathogenic variant in the SRY gene in a patient with 46,XY gonadal dysgenesis. An exome screen of a sub-group of 44 patients with 46,XY DSD revealed pathogenic or likely pathogenic variants in 38.6% (17/44) of patients. CONCLUSION: Rare or novel pathogenic variants were identified in the AR, SRD5A2, ZNRF3, SOX8, SOX9 and HHAT genes. Overall our data indicate a genetic diagnosis rate of 41.2% (68/165) in the group of 46,XY DSD.

Birth registration coverage according to the sex of the head of household: an analysis of national surveys from 93 low- and middle-income countries.

BACKGROUND: Within-country inequalities in birth registration coverage (BRC) have been documented according to wealth, place of residence and other household characteristics. We investigated whether sex of the head of household was associated with BRC. METHODS: Using data from nationally-representative surveys (Demographic and Health Survey or Multiple Indicator Cluster Survey) from 93 low and middle-income countries (LMICs) carried out in 2010 or later, we developed a typology including three main types of households: male-headed (MHH) and female-led with or without an adult male resident. Using Poisson regression, we compared BRC for children aged less than 12 months living the three types of households within each country, and then pooled results for all countries. Analyses were also adjusted for household wealth quintiles, maternal education and urban-rural residence. RESULTS: BRC ranged from 2.2% Ethiopia to 100% in Thailand (median 79%) while the proportion of MHH ranged from 52.1% in Ukraine to 98.3% in Afghanistan (median 72.9%). In most countries the proportion of poor families was highest in FHH (no male) and lowest in FHH (any male), with MHH occupying an intermediate position. Of the 93 countries, in the adjusted analyses, FHH (no male) had significantly higher BRC than MHH in 13 countries, while in eight countries the opposite trend was observed. The pooled analyses showed t BRC ratios of 1.01 (95% CI: 1.00; 1.01) for FHH (any male) relative to MHH, and also 1.01 (95% CI: 1.00; 1.01) for FHH (no male) relative to MHH. These analyses also showed a high degree of heterogeneity among countries. CONCLUSION: Sex of the head of household was not consistently associated with BRC in the pooled analyses but noteworthy differences in different directions were found in specific countries. Formal and informal benefits to FHH (no male), as well as women's ability to allocate household resources to their children in FHH, may explain why this vulnerable group has managed to offset a potential disadvantage to their children.

Inequalities in antenatal care coverage and quality: an analysis from 63 low and middle-income countries using the ANCq content-qualified coverage indicator.

BACKGROUND: Antenatal care (ANC) is an essential intervention associated with a reduction of maternal and new-born morbidity and mortality. However, evidence suggested substantial inequalities in maternal and child health, mainly in low- and middle-income countries (LMICs). We aimed to conduct a global analysis of socioeconomic inequalities in ANC using national surveys from LMICs. METHODS: ANC was measured using the ANCq, a novel content-qualified ANC coverage indicator, created and validated using national surveys, based upon contact with the health services and content of care received. We performed stratified analysis to explore the socioeconomic inequalities in ANCq. We also estimated the slope index of inequality, which measures the difference in coverage along the wealth spectrum. RESULTS: We analyzed 63 national surveys carried out from 2010 to 2017. There were large inequalities between and within countries. Higher ANCq scores were observed among women living in urban areas, with secondary or more level of education, belonging to wealthier families and with higher empowerment in nearly all countries. Countries with higher ANCq mean presented lower inequalities; while countries with average ANCq scores presented wide range of inequality, with some managing to achieve very low inequality. CONCLUSIONS: Despite all efforts in ANC programs, important inequalities in coverage and quality of ANC services persist. If maternal and child mortality Sustainable Development Goals are to be achieved, those gaps we documented must be bridged.

Pituitary apoplexy of a giant prolactinoma during pregnancy.

AIMS AND METHODS: Prolactinomas are a common cause of sexual dysfunction and infertility. We aimed, through this case report, to illustrate the difficulties of management of women with giant prolactinoma, especially in cases of desire of pregnancy. RESULTS: A 30-year-old woman was referred to our department for secondary amenorrhea. Investigations showed a prolactin level of 5168 ng/mL and giant pituitary adenoma of 4 cm in diameter. Cytoreductive surgery was performed after failure to normalize prolactin levels during three years with medical treatment by cabergoline. After seven months, menstrual cycles have resumed, and after 13 months, the patient became pregnant. At 22nd week of gestation, she was admitted in our hospital for pituitary apoplexy. Medical treatment with bromocriptine was chosen. The vaginal premature delivery at 28 weeks gave birth to twins weighing 1 Kg each who died on the 7th day of life. CONCLUSION: This is a relevant clinical case that illustrates the efficacy of cytoreductive surgery in case of insufficient response to dopamine agonists to restore gonadal function. The possibility of a pregnancy should be considered in these patients since it can be associated with high maternal and fetal risks.

Comparative analysis of the diagnostic performance of adult, cercarial and egg antigens assessed by ELISA, in the diagnosis of chronic human Schistosoma mansoni infection.

Total IgG ELISA was assessed comparing soluble adult worm (SWA), cercarial (SCA), and egg antigens (SEA) using sera of chronic schistosomiasis patients in two different concentrations (1/50 and 1/100). This response showed reactivity against all antigens. Concerning 1/100 serum concentration the SWA gave the best sensitivity (100%) followed by SCA (86.6%) and SEA (80%). The best specificity was obtained from SCA (94.11%) with an equivalent result from the SWA and SEA (76.47%). Concerning the 1/50 serum concentration, the SWA gave the best sensitivity (100%) with an equivalent result from the SCA and SEA (80%). The best specificity was obtained from SEA (82.35%) followed by SCA (76.47%) then SWA (64.7%). The best AUC value (0.992) was that for SWA indicating its high ability to predict the disease in comparison to (0.914) for SCA and 0.871 for SEA in serum dilution 1/100. The highest AUC value (0.955) was that for SWA in comparison to (0.914) for SEA and (0.88) for SCA in serum dilution 1/50. Comparison between the AUCs from the three mentioned antigens revealed highly significant differences when the data were analyzed by ROC. Each antigen showed a highly statistically significant correlation within its optical density values at both concentrations; 1/100 and 1/50. Comparing the two concentrations in each antigen revealed a non significant correlation obtained from the SWA which signifies a near outcome from both concentrations while the SCA and SEA showed a highly significant difference between the two concentrations. In conclusion, for the diagnosis of chronic schistosomiasis mansoni, total IgG reactivity revealed the best sensitivity by SWA. There was a difference in the type of antigen showing best specificity results between SCA and SEA according to serum concentration used.

Pituitary gland metastasis of breast cancer presenting as diabetes insipidus: A case report.

Metastasis to pituitary gland is a rare condition, and patients are usually asymptomatic. Diabetes insipidus (DI) is the most common presenting symptom, and breast cancer is the most common source of pituitary metastasis (PM). We report a case of PM of breast cancer presenting as DI. A 45-year-old female patient presented to our department with complaints of polyuria and polydipsia. She had a medical history of metastatic breast adenocarcinoma. Laboratory data showed normal fasting plasma glucose level and hypotonic urine. Brain magnetic resonance imaging (MRI) showed infiltration of the pituitary stalk and the absence of the posterior pituitary bright spot consistent with metastasis to the pituitary gland. The water deprivation and vasopressin challenge tests confirmed central DI. Pituitary function tests revealed disconnection hyperprolactinemia with a menopausal profile. The patient was treated with vasopressin with great clinical results. Pituitary metastases are rare but should be suspected in patients with metastatic cancer who present with DI.

Dot-blot immunoassay of Fasciola gigantica infection using 27 kDa and adult worm regurge antigens in Egyptian patients.

The purpose of the present study was to evaluate the potential role of the 27-Kilodalton (KDa) antigen versus Fasciola gigantica adult worm regurge antigens in a DOT-Blot assay and to assess this assay as a practical tool for diagnosis fascioliasis in Egyptian patients. Fasciola gigantica antigen of an approximate molecular mass 27-(KDa) was obtained from adult worms by a simple elution SDS-PAGE. A Dot-Blot was developed comparatively to adult worm regurge antigens for the detection of specific antibodies from patients infected with F. gigantica in Egypt. Control sera were obtained from patients with other parasitic infections and healthy volunteers to assess the test and compare between the antigens. The sensitivity, specificity, positive and negative predictive values of Dot-Blot using the adult worm regurge were 80%, 90%, 94.1%, and 69.2% respectively, while those using 27-KDa were 100% which confirms the diagnostic potential of this antigen. All patients infected with Fasciola were positive, with cross reactivity reported with Schistosoma mansoni serum samples. This 27-KDa Dot-Blot assay showed to be a promising test which can be used for serodiagnosis of fascioliasis in Egyptian patients especially, those presenting with hepatic disease. It is specific, sensitive and easy to perform method for the rapid diagnosis particularly when more complex laboratory tests are unavailable.

Permeation enhancers loaded bilosomes for improved intestinal absorption and cytotoxic activity of doxorubicin.

The clinical utility of doxorubicin is compromised due to dose related toxic side effects and limited oral bioavailability with no oral formulation being marketed. Enhancement of intestinal absorption and magnification of cytotoxicity can overcome these limitations. Accordingly, the objective was to probe penetration enhancers, bilosomes and their combinations for enhanced intestinal absorption and improved cytotoxicity of doxorubicin. Piperine and dipyridamole were tested as enhancers alone or encapsulated in bilosomes comprising Span60, cholesterol and bile salts. Bilosomes were nanosized spherical vesicles with negative zeta potential and were able to entrap doxorubicin with efficiency ranging from 45.3 % to 53 %. Intestinal absorption studies utilized in-situ rabbit intestinal perfusion which revealed site dependent doxorubicin absorption correlating with regional distribution of efflux transporters. Co-perfusion with the enhancer increased intestinal absorption with further augmentation after bilosomal encapsulation. The latter increased the % fraction absorbed by 4.5-6 and 1.8-2.5-fold from jejuno-ileum and colon, respectively, depending on bilosomes composition. Additionally, doxorubicin cytotoxicity against breast cancer cells (MCF-7) was significantly improved after bilosomal encapsulation and the recorded doxorubicin IC50 value was reduced from 13.3 µM to 0.1 µM for the best formulation. The study introduced bilosomes encapsulating absorption enhancers as promising carriers for enhanced cytotoxicity and oral absorption of doxorubicin.

Women's marital status and use of family planning services across male- and female-headed households in low- and middle-income countries.

Background: As more households are being led by women, who are often seen as disadvantaged, more attention is being given to the potential association of female household headship with health. We aimed to assess how demand for family planning satisfied by modern methods (mDFPS) is associated with residence in female or male headed households and how this intersects with marital status and sexual activity. Methods: We used data from national health surveys carried out in 59 low- and middle-income countries between 2010 and 2020. We included all women aged 15 to 49 years in our analysis, regardless of their relationship with the household head. We explored mDFPS according to household headship and its intersectionality with the women's marital status. We identified households as male-headed households (MHH) or female-headed households (FHH), and classified marital status as not married/in a union, married with the partner living in the household, and married with the partner living elsewhere. Other descriptive variables were time since the last sexual intercourse and reason for not using contraceptives. Results: We found statistically significant differences in mDFPS by household headship among reproductive age women in 32 of the 59 countries, with higher mDFPS among women living in MHH in 27 of these 32 countries. We also found large gaps in Bangladesh (FHH = 38%, MHH = 75%), Afghanistan (FHH = 14%, MHH = 40%) and Egypt (FHH = 56%, MHH = 80%). mDFPS was lower among married women with the partner living elsewhere, a common situation in FHH. The proportions of women with no sexual activity in the last six months and who did not use contraception due to infrequent sex were higher in FHH. Conclusions: Our findings indicate that a relationship exists between household headship, marital status, sexual activity, and mDFPS. The lower mDFPS we observed among women from FHH seems to be primarily associated with their lower risk of pregnancy; although women from FHH are married, their partners frequently do not live with them, and they are less sexually active than women in MHH.

Measures of women's empowerment based on individual-level data: a literature review with a focus on the methodological approaches.

Background: Quantifying women's empowerment has become the focus of attention of many international organizations and scholars. We aimed to describe quantitative indicators of women's empowerment that are based on individual-level data. Methods: In this scoping review, we searched PubMed, Scopus, Web of Science, Science Direct, Google, and Google Scholar for publications describing the operationalization of measures of women's empowerment. Results: We identified 36 studies published since 2004, half of them since 2019, and most from low- and middle-income countries. Twelve studies were based on data from the Demographic and Health Surveys and used 56 different variables from the questionnaires (ranging from one to 25 per study) to measure the overall empowerment of women 15-49 years. One study focused on rural women, two included married and unmarried women, and one analyzed the couple's responses. Factor analysis and principal component analysis were the most common approaches used. Among the 24 studies based on other surveys, ten analyzed overall empowerment, while the others addressed sexual and reproductive health (4 studies), agriculture (3) and livestock (1), water and sanitation (2), nutrition (2), agency (1), and psychological empowerment (1). These measures were mainly based on data from single countries and factor analysis was the most frequently analytical method used. We observed a diversity of indicator definitions and domains and a lack of consensus in terms of what the proposed indicators measure. Conclusion: The proposed women's empowerment indicators represent an advance in the field of gender and development monitoring. However, the empowerment definitions used vary widely in concept and in the domains/dimensions considered, which, in turn influence or are influenced by the adopted methodologies. It remains a challenge to find a balance between the need for a measure suitable for comparisons across populations and over time and the incorporation of country-specific elements.

Esthesioneuroblastoma presenting as syndrome of inappropriate antidiuretic hormone secretion.

Hyponatremia is the most common fluid electrolyte disorder in hospitalized patients. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the main cause of normovolemic hyponatremia, it can be caused by diverse etiologies: malignant tumors are the most feared cause that clinician persists in finding. Exceptionally, SIADH can complicate Esthesioneuroblastoma (ENB) or olfactory neuroblastoma, a rare tumor of the nasal sinus cavities. We report the case of a 26-year-old female patient admitted for recurrent headaches and vomiting, with a profound normovolemic hyponatremia at the initial assessment. Biological explorations have concluded in a SIADH. Imaging showed a mass of the left nasal cavity with extensions to the ipsilateral paranasal sinuses. The biopsy of the lesion, under endoscopic control, was inconclusive. The anatomopathological study, after surgical removal, concluded in ENB. The postoperative evolution was marked by the normalization of the natremia.

Positive myositis-specific autoantibodies during COVID-19: a case report.

Viral infection is known to be a trigger of autoimmune diseases. Numerous cases of coronavirus disease 2019 (COVID-19) with autoimmune manifestations have been reported and several authors have highlighted the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and autoimmune diseases. Autoimmune myopathies being one of these manifestations. A 27-year-old diabetic woman was admitted for management of acido-ketosis decompensation of her diabetes secondary to SARS-CoV-2 infection. During hospitalization, she developed muscle weakness and increased creatine kinase levels, which led us to assay the autoimmunity pattern which became positive for myositis-specific autoantibodies against single recognition particle (anti-SRP). The patient was treated with intense hydration with clinical and biological improvement and anti-SRP disappeared two months later. Positive myositis auto-antibodies are one of the autoimmune complications that could be seen during and after the SARS-CoV-2 infection.

Paving the way to understanding female-headed households: Variation in household composition across 103 low- and middle-income countries.

Background: Female-headed households (FHHs) are regarded as disadvantaged. There are multiple social trajectories that can lead to women heading households. It is important to distinguish between these trajectories, as well as societal norms and contextual factors, to understand how and when are FHHs represented as a dimension of gender inequity. Our analysis defines and describes a typology of 16 FHH types (FHH16) based on demographic characteristics. Methods: This cross-sectional study used national Demographic Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) in 103 low- and middle-income countries (LMICs) to identify a typology of FHHs based on the family composition and additional household members. We performed descriptive analyses at the household level to generate median proportions of the FHH16 types and selected household characteristics. We conducted cluster analyses to explore FHH16 patterns across naturally grouped clusters of countries and described selected social and economic indicators at the ecological level. Results: The most common FHH16 types were those where the women household heads lived with children only, were alone, or lived with men, women, and children, but without a husband. In Africa and South Asia, the most common FHH was one where women heads resided with children only. In East Asia and the Pacific, the highest proportion of FHHs were those with men, women, and children. In MENA and Eastern Europe & Central Asia, households with women heads living alone were the most prevalent. Latin America had more FHHs with husbands, comparatively, and the most common FHHs were those with heads living alone or with children. Our exploratory cluster analysis generated five clusters with unique FHH16 patterns. The clusters had distinct geographic, contextual and economic characteristics. Conclusions: Our typology showed that FHHs are heterogeneous within and between countries. The ecological analysis emphasized further variation created by different societal and cultural factors. Research around their vulnerabilities and strengths needs to consider these factors and their influence on socioeconomic status and health-related outcomes within households headed by women.

Safety Assessment and Potential Risks of the Glucagon Stimulation Test in the Diagnosis of Secondary Adrenal Insufficiency.

BACKGROUND: Although it takes more time, the Glucagon Stimulation Test (GST) is a reliable measure for assessing growth hormone (GH) and Adrenocorticotropic Hormone (ACTH) secretion. The GST is considered to be a safe test; however, it still has mild side effects and potential risks. OBJECTIVES: The objective of this study was to analyze the side effects of the GST while testing adrenal-insufficient patients. METHODS: This was a prospective study in which GST was performed in eighty-one patients (44 men, 37 women, mean age: 35.83A9.62 years) with the pituitary disorder. The GST consisted of an intramuscular injection of 1 mg of glucagon. Blood samples were collected at baseline, and 30, 60, 90, 120, 150, 180, and 210 min after glucagon injection for cortisol measurements. All patients were asked to report side effects associated with this test. RESULTS: The mean peak blood glucose level under GST was 9.01A.03 mmol/L, and the mean glycemic nadir was 4.34A.75 mmol/L most frequently found during the 30th minute (p <10-3). During the test, 35 subjects (43.2%) had side effects with a mean age of 42.89 A19.75 years. Frequent side effects included: nausea (29.62%), vomiting (27.16%), abdominal cramps (18.51%) and hunger (13.58%). All patients tolerated the test until the end. Adverse effects were significantly more prevalent in patients older than 50 years (p=0.012). CONCLUSIONS: The GST is a reliable alternative to assess the hypothalamic pituitary adrenal axis but should be cautiously used especially in the elderly, despite minor side effects.

A new content-qualified antenatal care coverage indicator: Development and validation of a score using national health surveys in low- and middle-income countries.

BACKGROUND: Good quality antenatal care (ANC) helps reduce adverse maternal and newborn outcomes, especially in low and middle-income countries (LMICs). Most of the currently used ANC indicators only measure contact with services. We aimed to create and validate a new indicator measured as a score, considering both contact and content, that can be used for monitoring. METHODS: We used data from national surveys conducted in LMICs. Information on ANC was used to build an adequacy score (ANCq) that would be applicable to all women in need of ANC. Cronbach's alpha and factor analysis were used to assess the proposed indicator. We also used a convergent validation approach, exploring the association of our proposed indicator with neonatal mortality. RESULTS: The ANCq score was derived from seven variables related to contact with services and content of care ranging from zero to ten. Surveys from 63 countries with all variables were used. The validity assessment showed satisfactory results based on Cronbach's alpha (0.82) and factor analysis. The overall mean of ANCq was 6.7, ranging from 3.5 in Afghanistan to 9.3 in Cuba and the Dominican Republic. In most countries, the ANCq was inversely associated with neonatal mortality and the pooled for all surveys Odds Ratio was 0.90 (95% CI = 0.88-0.92). CONCLUSIONS: ANCq allows the assessment of ANC in LMICs considering contact with services and content of care. It also presented good validity properties, being a useful tool for assessing ANC coverage and adequacy of care in monitoring and accountability exercises.

Association of an empty sella and grave´s disease in a patient with acromegaly: a case report.

Acromegaly is, in most cases, caused by growth hormone secreting pituitary adenomas. Those patients often develop different pathologies of the thyroid gland, however, the occurrence of Grave´s disease is quite a rare situation. We report a case of a 64-year-old female patient who presented with signs of hyperthyroidism and imbalance of her diabetes mellitus. On physical examination, she had facial features of acromegaly. Biochemical testing confirmed the suspicion of acromegaly and Grave´s disease, with an elevated insulin-like growth factor-1 and a suppressed thyroid stimulation hormone (TSH) with positive TSH-receptor antibodies. A pituitary Magnetic Resonance Imaging (MRI) was performed, revealing a macro-adenoma and an empty sella. The patient successfully underwent a transsphenoidal surgery and obtained a remission of her hyperthyroidism under anti-thyroid drugs.

Are children in female-headed households at a disadvantage? An analysis of immunization coverage and stunting prevalence: in 95 low- and middle-income countries.

Studies of inequalities in child health have given limited attention to household structure and headship. The few existing reports on child outcomes in male and female-headed households have produced inconsistent results. The aim of our analyses was to provide a global view of the influence of sex of the household head on child health in cross-sectional surveys from up to 95 LMICs. Studied outcomes were full immunization coverage in children aged 12-23 months and stunting prevalence in under-five children. We analyzed the most recent nationally-representative surveys for each country (since 2010) with available data. After initial exploratory analyses, we focused on three types of households: a) male-headed household (MHH) comprised 73.1% of all households in the pooled analyses; b) female Headed Household (FHH) with at least one adult male represented 9.8% of households; and c) FHH without an adult male accounted for 15.0% of households. Our analyses also included the following covariates: wealth index, education of the child's mother and urban/rural residence. Meta-analytic approaches were used to calculate pooled effects across the countries with MHH as the reference category. Regarding full immunization, the pooled prevalence ratio for FHH (any male) was 0.99 (0.97; 1.01) and that for FHH (no male) was 0.99 (0.97; 1.02). For stunting prevalence, the pooled prevalence ratio for FHH (any male) was 1.00 (0.98; 1.02) and for FHH (no male) was 1.00 (0.98; 1.02). Adjustment for covariates did not lead to any noteworthy change in the results. No particular patterns were found among different world regions. A few countries presented significant inequalities with different directions of association, indicating the diversity of FHH and how complex the meaning and measurement of household headship may be. Further research is warranted to understand context, examine mediating factors, and exploring alternative definitions of household headship in countries with some association.

Prostatic tissue in 46XX congenital adrenal hyperplasia: Case report and literature review.

The presence of prostatic tissue, in addition to uterus and adrenal tumors, is possible in 46XX patients with CAH. Lesions of these organs are usually benign. However, complications including prostate and adrenal cancer were also reported.

Disorders of sodium balance in COVID-19 patients: two Tunisian patients report.

Coronavirus disease 2019 (COVID-19) was first reported in December 2019. The disease is caused by severe acute respiratory syndrome virus corona virus 2 (SARS-CoV-2). Mild respiratory symptoms are the most common manifestations of SARS-CoV-2, but new signs are constantly being discovered as it spreads. Disorders of sodium balance are increasingly described in patients with SARS-CoV-2. We report, here, the cases of two patients presented with COVID-19 and in whom we discovered sodium disorders. The first patient is a 74-year-old man who presented with fatal hypernatremia. The second patient is a 66-years-old man presented with COVID-19 and euvolemic hyponatremia attributed to syndrome of inappropriate anti-diuretic hormone secretion (SIADH). This hyponatremia persisted long after the respiratory signs disappeared. Sodium balance disorders are increasingly described in the literature; special attention should be paid to the electrolyte status of COVID-19 patients. Pathophysiological mechanisms associating SARS-CoV-2 with these disorders are being studied.

Congenital adrenal hyperplasia due to 11-Beta-hydroxylase deficiency in a Tunisian family.

Congenital adrenal hyperplasia refers to a group of rare genetic disorders affecting the adrenal glands. 21-hydroxylase deficiency is the most prevalent and the most studied cause while the remaining enzymatic defects are less common, accounting for less than 10% of cases. We herein described the clinical, biological and molecular characteristics and outcome of patients of the same family diagnosed with 11-Beta-hydroxylase deficiency. The disorder was revealed by peripheral precocious puberty between the age of 2-3 years in males and by the virilization of the external genitalia in females. Genetics finding a homozygous p.Gly379Val mutation in the CYP11B1 gene. All patients received hydrocortisone supplementation therapy and mineralocorticoid-receptor antagonist. The females underwent a surgical correction of the ambiguous genitalia at the neonatal age. Long term follow-up revealed metabolic syndrome, obesity and hypertension in the first two patients, an impaired final height in the two females and hypokalemia in three patients.