The impact of craniofacial and dental osteogenesis imperfecta manifestations on oral health-related quality of life of children and adolescents.

OBJECTIVE: Craniofacial and oral manifestations of Osteogenesis Imperfecta (OI) can affect the functioning of the stomatognathic system and impact the patient's quality of life. The objective of the study was to evaluate the relationship between craniofacial and oral manifestations and the Oral Health-related Quality of Life (OHRQoL) of OI children and adolescents. MATERIAL AND METHODS: A total of 30 OI patients aged eight to fourteen years old followed up at the Oral Care Center for Inherited Diseases were enrolled in the research. OHRQoL was assessed using the short form of the Child Perceptions Questionnaire (CPQ) for eight to ten-year-olds (CPQ8-10) and 11 to 14-year-olds (CPQ11-14). The relationship between the OHRQoL index and its assessment domains, OI types, and the presence of dentinogenesis imperfecta (DI), class III malocclusion, and dental agenesis were evaluated. RESULTS: The median CPQ score of patients was 5, and there was no significant difference in OHRQoL between children and adolescents, nor associated with the disease severity or the presence of DI. The oral manifestations evaluated did not directly impact the patients' OHRQoL. CONCLUSIONS: The study demonstrated that the perception of OHRQoL is similar for both adolescents and children. The oral symptom was the most relevant domain for the index among patients aged eight to fourteen years while the emotional well-being was the most impacted. CLINICAL RELEVANCE: this study makes contributions by indicating that addressing dental care for children and adolescents with OI is important in clinical management and better OHRQoL for this population.

Pamidronate Therapy Increases Trabecular Bone Complexity of Mandibular Condyles in Individuals with Osteogenesis Imperfecta.

Patients with Osteogenesis Imperfecta (OI) present extra-skeletal manifestations, including important orodental and craniofacial features as dentinogenesis imperfecta, dental agenesis, failure of maxilla growth and hypotonia of masticatory muscles. These features may compromise vital functions speech and mastication. Studies have demonstrated that cyclic pamidronate infusion, the standard therapy for patients with moderate to severe OI, influences the histomorphometric pattern of different body bones. The present study aimed to investigate the condyle trabecular bone pattern in OI patients. We used fractal dimension (FD) analysis on dental panoramic radiographic images to characterize the mandibular condyle trabecular bone in adolescents diagnosed with OI and treated with pamidronate. Imaging exam of 33 adolescents of both sexes, aged between 12 and 17 years, were analyzed and compared with 99 age- and sex-matched healthy adolescents. FD in patients was significantly lower (1.23 ± 0.15) than in healthy controls (1.29 ± 0.11; p < 0.01). Type of OI, age at treatment onset, and the duration of therapy were variables that showed a statistically significant effect on the FD results. This study demonstrated that the bone architecture of mandibular condyles may be altered in pediatric patients with moderate and severe forms of OI. Also, pamidronate treatment seems to have a positive effect on condyle trabecular bone in these patients. This is supported by our finding that FD values were positively influenced by the length of cyclic pamidronate treatment at the time of imaging, as well as by the age of the individual at treatment onset.

SHORT syndrome in an adult Brazilian patient.

We report an individual from Brazil with SHORT syndrome. The term SHORT stands for its common characteristics: short stature (S), hyperextensibility of joints, and/or inguinal hernia (H), ocular depression (O), Rieger anomaly (R), and teething delay (T). In addition to most of the clinical signs previously described in SHORT syndrome, the patient presented here also shows microcephaly and intellectual disability. Diagnosis was confirmed by exome sequencing revealing a novel heterozygous variant c.1456G>A (p.Ala486Thr) at PIK3R1. Human recombinant growth hormone (r-hGH) therapy was administered prior to diagnosis; however, the use of r-hGH may have had a role in anticipating and worsening the glucose metabolic profile in the patient, as previously described. This article contributes to providing a better understanding of the SHORT syndrome genotype and its correlation with the phenotype, by comparing with it other reported cases.

Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused by CLDN19 gene mutations.

BACKGROUND: Amelogenesis imperfecta (AI) is a group of genetic diseases characterised by tooth enamel defects. AI was recently described in patients with familial hypercalciuria and hypomagnesaemia with nephrocalcinosis (FHHNC) caused by CLDN16 mutations. In the kidney, claudin-16 interacts with claudin-19 to control the paracellular passage of calcium and magnesium. FHHNC can be linked to mutations in both genes. Claudin-16 was shown to be expressed during amelogenesis; however, no data are available on claudin-19. Moreover, the enamel phenotype of patients with CLDN19 mutations has never been described. In this study, we describe the clinical and genetic features of nine patients with FHHNC carrying CLDN19 mutations and the claudin-19 expression profile in rat ameloblasts. METHODS: Six FHHNC Brazilian patients were subjected to mutational analysis. Three additional French patients were recruited for orodental characterisation. The expression profile of claudin-19 was evaluated by RT-qPCR and immunofluorescence using enamel epithelium from rat incisors. RESULTS: All patients presented AI at different degrees of severity. Two new likely pathogenic variations in CLDN19 were found: p.Arg200Gln and p.Leu90Arg. RT-qPCR revealed low Cldn19 expression in ameloblasts. Confocal analysis indicated that claudin-19 was immunolocalised at the distal poles of secretory and maturing ameloblasts. CONCLUSIONS: For the first time, it was demonstrated that AI is associated with FHHNC in patients carrying CLDN19 mutations. The data suggest claudin-19 as an additional determinant in enamel formation. Indeed, the coexistence of hypoplastic and hypomineralised AI in the patients was consistent with claudin-19 expression in both secretory and maturation stages. Additional indirect systemic effects cannot be excluded.

NPHS1 gene mutations confirm congenital nephrotic syndrome in four Brazilian cases: A novel mutation is described.

AIM: Autosomal recessive mutations in NPHS1 gene are a common cause of congenital nephrotic syndrome (CNS). The disorder is characterized by massive proteinuria that manifests in utero or in the neonatal period during the first 3 months of life. NPHS1 encodes nephrin, a member of the immunoglobulin family of cell adhesion molecules and the main protein expressed at the renal slit diaphragm. Currently, there are approximately 250 mutations described in the NPHS1 gene distributed among all nephrin domains. The main objective of this study was to perform the analysis of the NPHS1 gene in patients with congenital nephrotic syndrome in order to determine the molecular cause of the disease. METHODS: Direct sequencing of NPHS1 gene in four children was performed. RESULTS: Each patient was heterozygous for two pathogenic mutations disclosing the molecular cause of the disease in 100% of the cases. We identified six different mutations, consisting of one in-frame deletion, one frameshift, and four missense substitutions. The p.Val736Met mutation that is described here for the first time was considered pathogenic by different mutation predictive algorithms. Regardless of the type of mutation, three patients had a bad outcome and died CONCLUSIONS: Despite the small size of the cohort, this study contributed to the increasing number of deleterious mutations in the NPHS1 gene by describing a new mutation. Also, since we identified NPHS1 pathogenic mutations as the cause of the disease in all cases analyzed, it might be a frequent cause of CNS in the South Eastern region of Brazil, although the analysis of a larger sample is required to obtain more indicative epidemiological data.

Variability of systemic and oro-dental phenotype in two families with non-lethal Raine syndrome with FAM20C mutations.

BACKGROUND: Raine syndrome (RS) is a rare autosomal recessive bone dysplasia typified by osteosclerosis and dysmorphic facies due to FAM20C mutations. Initially reported as lethal in infancy, survival is possible into adulthood. We describe the molecular analysis and clinical phenotypes of five individuals from two consanguineous Brazilian families with attenuated Raine Syndrome with previously unreported features. METHODS: The medical and dental clinical records were reviewed. Extracted deciduous and permanent teeth as well as oral soft tissues were analysed. Whole exome sequencing was undertaken and FAM20C cDNA sequenced in family 1. RESULTS: Family 1 included 3 siblings with hypoplastic Amelogenesis Imperfecta (AI) (inherited abnormal dental enamel formation). Mild facial dysmorphism was noted in the absence of other obvious skeletal or growth abnormalities. A mild hypophosphataemia and soft tissue ectopic mineralization were present. A homozygous FAM20C donor splice site mutation (c.784 + 5 g > c) was identified which led to abnormal cDNA sequence. Family 2 included 2 siblings with hypoplastic AI and tooth dentine abnormalities as part of a more obvious syndrome with facial dysmorphism. There was hypophosphataemia, soft tissue ectopic mineralization, but no osteosclerosis. A homozygous missense mutation in FAM20C (c.1487C > T; p.P496L) was identified. CONCLUSIONS: The clinical phenotype of non-lethal Raine Syndrome is more variable, including between affected siblings, than previously described and an adverse impact on bone growth and health may not be a prominent feature. By contrast, a profound failure of dental enamel formation leading to a distinctive hypoplastic AI in all teeth should alert clinicians to the possibility of FAM20C mutations.

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study.

Introduction: SARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators. Methods: A sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array. Results: In the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester. Discussion and conclusion: From an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women.

Evaluation of 25-hydroxy-vitamin D and parathyroid hormone in Callithrix penicillata primates living in their natural habitat in Brazil.

BACKGROUND: Vitamin D is a secosteroid hormone with important roles in the control of bone and mineral metabolism of vertebrates and in the maintenance of systemic homeostasis. This study aimed (i) to evaluate the serum concentrations of 25-hydroxy-vitamin D levels [25(OH)D], parathyroid hormone (PTH) and ionized calcium (iCa) of wild Callithrix penicillata (black-tufted marmosets) and (ii) to propose reference ranges for those analytes for free-living marmosets. METHODS: Blood samples were collected from 15 wild animals and analyzed for 25(OH)D, PTH and iCa. Reference values were calculated following standard analytical criteria. RESULTS: The observed mean serum levels (±standard deviation) were 25(OH)D, 61.7 (±20.8) ng/ml; PTH, 275.2 (±34.1) pg/ml; iCai 4.0 (±0.6) mg/dl. CONCLUSIONS: For free-living marmosets, the proposed physiological range for 25(OH)D is 20.1-103.3 ng/ml and for PTH is 207.0-343.3 pg/dl, with a confidence interval of 95%.

Official Position of the Brazilian Association of Bone Assessment and Metabolism (ABRASSO) on the evaluation of body composition by densitometry-part II (clinical aspects): interpretation, reporting, and special situations.

OBJECTIVE: To present an updated and evidence-based guideline for the use of dual-energy x-ray absorptiometry (DXA) to assess body composition in clinical practice. MATERIALS AND METHODS: This Official Position was developed by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism (Associação Brasileira de Avaliação Óssea e Osteometabolismo, ABRASSO) and experts in the field who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications in the area of body composition assessment. In this second part of the Official Position, the authors discuss the interpretation and reporting of body composition parameters assessed by DXA and the use of DXA for body composition evaluation in special situations, including evaluation of children, persons with HIV, and animals. CONCLUSION: This document offers recommendations for the use of DXA in body composition evaluation, including indications, interpretation, and applications, to serve as a guiding tool in clinical practice and research for health care professionals in Brazil.

Postural balance, handgrip strength and mobility in Brazilian children and adolescents with osteogenesis imperfecta.

OBJECTIVE: To describe postural balance, handgrip strength and mobility in children and adolescents with different types of osteogenesis imperfecta. METHODS: Cross-sectional study. Fifty selected subjects diagnosed with types I (n=11), III (n=21), and IV (n=18), followed up at Brazilian reference center for osteogenesis imperfecta in the Midwest region, aged 2-21 years (9.2±5.0), were enrolled in this study. Children and adolescents were evaluated for postural balance in the upright position with eyes-open and eyes-closed conditions, handgrip strength and the mobility domain (Pediatric Dysfunction Assessment Inventory). Data normality and difference between groups was verified. RESULTS: Handgrip strength was significantly lower in people with type III of osteogenesis imperfecta when compared to the osteogenesis imperfecta types I and IV, and to the age-specific reference data. Center of pressure length and mean velocity in the condition with eyes closed were worse compared to the open-eyes condition for children and adolescents with type I of osteogenesis imperfecta. There were worse results in the mobility domain for the participants classified with the most severe type of osteogenesis imperfecta. CONCLUSIONS: It was observed that the severity of the osteogenesis imperfecta disease affected handgrip strength and locomotor function assessed by the mobility domain. Comparing osteogenesis imperfecta types, the higher the severity of osteogenesis imperfecta, the lower the handgrip strength. These results can contribute to new strategies of treatment focused on improving functional capacity and quality of life in people with osteogenesis imperfecta.

Clinical and biochemical parameters of COVID-19 patients with prior or active dengue fever.

Originated in Wuhan, China, the coronavirus 19 disease (COVID-19) has quickly spread worldwide, reaching countries that already faced other endemics and epidemics. In Brazil, such a concerning situation includes arboviruses, among which the dengue virus stands out. Here, we determined the rate of SARS-CoV-2/dengue virus co-infection in a total of 178 patients with COVID-19 symtoms admitted into a large public hospital of the Federal District of Brazil. Furthermore, we evaluated whether prior or active dengue virus infection influenced hematological, biochemical, and clinical parameters of such patients. One hundred and twelve (63%) individuals tested positive for COVID-19, of which 43 (38.4%) were co-infected with dengue virus, and 50 (44.6%) had antibodies indicative of previous dengue infection. Co-infected patients showed lower numbers of circulating lymphocytes and monocytes, higher glucose rates, and a worse pulmonary condition. Of note, prior infections with dengue virus did not influence clinical parameters, but active dengue fever resulted in higher hospitalization rate. In conclusion, amid the current complex epidemiological scenario in Brazil, our data support the notion that SARS-CoV-2 and dengue co-infection affects an important percentage of COVID-19 patients and leads to worse clinical parameters, requiring greater attention from health authorities.

Do Molecular Profiles of Primary Versus Metastatic Radioiodine Refractory Differentiated Thyroid Cancer Differ?

Management of metastatic radioiodine refractory differentiated thyroid cancer (DTC) can be a therapeutic challenge. Generally, little is known about the paired molecular profile of the primary tumor and the metastases and whether they harbor the same genetic abnormalities. The present study compared the molecular profile of paired tumor specimens (primary tumor/metastatic sites) from patients with radioiodine refractory DTC in order to gain insight into a possible basis for resistance to radioiodine. Twelve patients with radioiodine refractory metastases were studied; median age at diagnosis of 61 years (range, 25-82). Nine patients had papillary TC (PTC), one had follicular TC (FTC), and two had Hürthle cell TC (HTC). Distant metastases were present in the lungs (n = 10), bones (n = 4), and liver (n = 1). The molecular profiling of paired tumors was performed with a panel of 592 genes for Next Generation Sequencing, RNA-sequencing, and immunohistochemistry. Digital microfluidic PCR was used to investigate TERT promoter mutations. The genetic landscape of all paired sites comprised BRAF, NRAS, HRAS, TP53, ATM, MUTYH, POLE, and NTRK genes, including BRAF and NTRK fusions. BRAF V600E was the most common point mutation in the paired specimens (5/12). TERT promoter mutation C228T was detected in one case. PD-L1 expression at metastatic sites was highly positive (95%) for one patient with HTC. All specimens were stable for microsatellite instability testing, and the tumor mutation burden was low to intermediate. Therefore, the molecular profile of DTC primary and metastatic lesions can show heterogeneity, which may help explain some altered responses to therapeutic intervention.

Pregnancy Outcomes and Child Development Effects of SARS-CoV-2 Infection (PROUDEST Trial): Protocol for a Multicenter, Prospective Cohort Study.

BACKGROUND: A growing body of evidence suggests that SARS-COV-2 infection during pregnancy may affect maternal-fetal outcomes and possibly result in implications for the long-term development of SARS-CoV-2-exposed children. OBJECTIVE: The PROUDEST (Pregnancy Outcomes and Child Development Effects of SARS-CoV-2 Infection Study) is a multicenter, prospective cohort study designed to elucidate the repercussions of COVID-19 for the global health of mothers and their children. METHODS: The PROUDEST trial comprises 2 prospective, sequential substudies. The PREGNANT substudy will clinically assess the effects of SARS-CoV-2 infection on pregnancy, childbirth, and puerperium from a mechanistic standpoint to elucidate the pregnancy-related inflammatory and immunological phenomena underlying COVID-19. Pregnant women aged 18-40 years who have been exposed (proven with laboratory tests) to SARS-CoV-2 (group A; n=300) will be compared to control subjects with no laboratory evidence of in-pregnancy exposure to the virus (group B; n=300). Subjects exposed to other infections during pregnancy will be excluded. The BORN substudy is a long-term follow-up study that will assess the offspring of women who enrolled in the prior substudy. It will describe the effects of SARS-CoV-2 exposure during pregnancy on children's growth, neurodevelopment, and metabolism from birth up to 5 years of age. It includes two comparison groups; group A (exposed; n=300) comprises children born from SARS-CoV-2-exposed pregnancies, and group B (controls; n=300) comprises children born from nonexposed mothers. RESULTS: Recruitment began in July 2020, and as of January 2021, 260 pregnant women who were infected with SARS-CoV-2 during pregnancy and 160 newborns have been included in the study. Data analysis is scheduled to start after all data are collected. CONCLUSIONS: Upon completion of the study, we expect to have comprehensive data that will provide a better understanding of the effects of SARS-CoV-2 infection and related inflammatory and immunological processes on pregnancy, puerperium, and infancy. Our findings will inform clinical decisions regarding the care of SARS-CoV-2-exposed mothers and children and support the development of evidence-based public health policies. TRIAL REGISTRATION: Brazilian Register of Clinical Trials RBR65QXS2; https://ensaiosclinicos.gov.br/rg/RBR-65qxs2. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26477.

25-hydroxy-vitamin D levels among Callithrix penicillata primate species raised in captivity.

BACKGROUND: Animals in captivity should receive adequate sunlight exposure for sufficient generation of vitamin D [25(OH)D]. In the present study, 25(OH)D serum levels of 84 Callithrix penicillata primates were evaluated. OBJECTIVES: To determine 25(OH)D levels of those animals; to evaluate the influence of gender and period of sunlight exposure on their 25(OH)D levels. METHODS: Three groups were evaluated: group 1 (n = 29) on free sunlight exposure; group 2 (n = 34) on partial sunlight exposure; group 3 (n = 21) without sunlight exposure. RESULTS: The obtained 25(OH)D values were: group 1, 121.2 +/- 33.3 ng/ml; group 2, 115.2 +/- 32.2 ng/ml; group 3, 53.3 +/- 10.4 ng/ml. Significant statistical differences were obtained between groups 1 and 3 (p < 0.001) and groups 2 and 3 (p < 0.001); no statistical difference was found between genders. CONCLUSION: Direct sunlight exposure is essential for 25(OH)D sufficiency and it is proposed that the 25(OH)D normal range for captive Callithrix penicillata would be from 104.8 to 137.1 ng/ml (CI = 95%).

Repercussion of COVID-19 Pandemic on Brazilians' Quality of Life: A Nationwide Cross-Sectional Study.

The COVID-19 outbreak, caused by Sars-Cov-2, was officially declared a global pandemic in February 2020, after an unexpected increase in hospitalization and mortality. When faced with this new disease, social and physical distancing and quarantine emerged as solutions to reduce virus transmission. This article examines the quality of life (QoL) of the Brazilian population's during this period of isolation, due to the COVID-19 pandemic by analyzing; physical, psychological, social, and economic aspects. An online survey was distributed from 27 May to 14 August of 2020. A total of 1859 surveys were completed. Our results indicate that Brazilians were more affected by economic and social aspects than psychological and physical. Unemployed participants and individuals who tested positive for COVID-19 presented the lowest QoL. Females showed worst QoL scores than males, but having children did not influence the score. Higher educational level was associated with a better perception of QoL. Not following social distancing guidelines presented better scores in the psychological domain than the ones following restrict or partial social distancing rules. This study is the first to evaluate adults' QoL related to the Sars-Cov-2 pandemic in Brazil at a national level. Our data may help health authorities identify the main factors affecting the QoL of the Brazilian population, thereby orientating them to recover after the pandemic.

MKRN3 Mutations in Central Precocious Puberty: A Systematic Review and Meta-Analysis.

MKRN3 mutations represent the most common genetic cause of central precocious puberty (CPP) but associations between genotype and clinical features have not been extensively explored. This systematic review and meta-analysis investigated genotype-phenotype associations and prevalence of MKRN3 mutations in CPP. The search was conducted in seven electronic databases (Cochrane, EMBASE, LILACS, LIVIVO, PubMed, Scopus, and Web of Science) for articles published until 4 September 2018. Studies evaluating MKRN3 mutations in patients with CPP were considered eligible. A total of 22 studies, studying 880 subjects with CPP, fulfilled the inclusion criteria. Eighty-nine subjects (76 girls) were identified as harboring MKRN3 mutations. Girls, compared with boys, exhibited earlier age at pubertal onset (median, 6.0 years; range, 3.0 to 7.0 vs 8.5 years; range, 5.9 to 9.0; P < 0.001), and higher basal FSH levels (median, 4.3 IU/L; range, 0.7 to 13.94 IU/L vs 2.45 IU/L; range, 0.8 to 13.70 IU/L; P = 0.003), and bone age advancement (ΔBA; median, 2.3 years; range, -0.9 to 5.2 vs 1.2 years; range, 0.0 to 2.3; P = 0.01). Additional dysmorphisms were uncommon. A total of 14 studies evaluating 857 patients were included for quantitative analysis, with a pooled overall mutation prevalence of 9.0% (95% CI, 0.04 to 0.15). Subgroup analysis showed that prevalence estimates were higher in males, familial cases, and in non-Asian countries. In conclusion, MKRN3 mutations are associated with nonsyndromic CPP and manifest in a sex-dimorphic manner, with girls being affected earlier. They represent a common cause of CPP in western countries, especially in boys and familial cases.

Insights on the phenotypic heterogenity of 11ß-hydroxylase deficiency: clinical and genetic studies in two novel families.

PURPOSE: 11ß-hydroxylase deficiency accounts for 5% of congenital adrenal hyperplasia cases. Diagnosis suspiction is classically based on the association between abnormal virilization, precocious puberty, and hypertension in 46XX or 46XY subjects. We investigated two families with siblings presenting with opposed clinical features, and provided a review of the mechanisms involved in mineralocorticoid-dependent phenotypic heterogeneity. METHODS: The coding region of the CYP11B1 gene of 4 patients was sequenced and familial segregation was confirmed. Clinical characterization and blood steroid profile were performed. RESULTS: Family 1 comprised a female and a male siblings who presented in middle childhood with genital ambiguity (Prader II) and precocious puberty, respectively, associated with hypertension. In the second decade of life, the woman had three full-term pregnancies, and then evolved normotensive with no treatment over a 5-year follow up. On the other hand, her brother had hypertensive end-organ damage at age 24. In family 2, a 2.9 year-old boy presented with precocious puberty and hypertension, whereas his 21 days-old sister had genital ambiguity (Prader III) and salt wasting. A homozygous exon 4 splice site mutation was identified (IVS4ds-1G > A; c.799 G > A) in family 1, while a nonsense mutation in exon 6 (p. Q356X; c.1066 C > T) was found in family 2. CONCLUSION: CYP11B1 mutations were associated with highly variable phenotypes, from mild to severe virilization, and early-onset hypertension or salt wasting. Further analysis of variants in other hypertension-related genes, steroid synthesis and metabolism compensatory pathways, and/or the investigation of chimeric CYP11B genes are needed to clarify the phenotypic heterogeneity in 11ß-hydroxylase deficiency.

Official Position of the Brazilian Association of Bone Assessment and Metabolism (ABRASSO) on the evaluation of body composition by densitometry—part II (clinical aspects): interpretation, reporting, and special situations

Abstract Objective: To present an updated and evidence-based guideline for the use of dual-energy x-ray absorptiometry (DXA) to assess body composition in clinical practice. Materials and methods: This Official Position was developed by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism ( Associação Brasileira de Avaliação Óssea e Osteometabolismo , ABRASSO) and experts in the field who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications in the area of body composition assessment. In this second part of the Official Position, the authors discuss the interpretation and reporting of body composition parameters assessed by DXA and the use of DXA for body composition evaluation in special situations, including evaluation of children, persons with HIV, and animals. Conclusion: This document offers recommendations for the use of DXA in body composition evaluation, including indications, interpretation, and applications, to serve as a guiding tool in clinical practice and research for health care professionals in Brazil.

Hypophosphatemic rickets and osteomalacia.

The hypophosphatemic conditions that interfere in bone mineralization comprise many hereditary or acquired diseases, all of them sharing the same pathophysiologic mechanism: reduction in the phosphate reabsorption by the renal tubuli. This process leads to chronic hyperphosphaturia and hypophosphatemia, associated with inappropriately normal or low levels of calcitriol, causing osteomalacia or rickets in children and osteomalacia in adults. X-linked hypophosphatemic rickets, autosomal-dominant hypophosphatemic rickets, and tumor-induced osteomalacia are the main syndromes involved in the hypophosphatemic rickets. Although these conditions exhibit different etiologies, there is a common link among them: increased activity of a phosphaturic factor, being the fibroblast growth factor 23 (FGF-23) the most studied one and to which is attributed a central role in the pathophysiology of the hyperphosphaturic disturbances. Activating mutations of FGF-23 and inactivating mutations in the PHEX gene (a gene on the X chromosome that codes for a Zn-metaloendopeptidase proteolytic enzyme which regulates the phosphate) involved in the regulation of FGF-23 have been identified and have been implicated in the pathogenesis of these disturbances. Genetic studies tend to show that the phosphorus homeostasis depends on a complex osteo-renal metabolic axis, whose mechanisms of interaction have been poorly understood so far. This paper reviews the current knowledge status concerning the pathophysiology of phosphate metabolism regulation and the pathophysiologic basis of hypophosphatemic rickets. It also analyzes the clinical picture and the therapeutic aspects of these conditions as well.

Postural balance, handgrip strength and mobility in Brazilian children and adolescents with osteogenesis imperfecta

Abstract Objective To describe postural balance, handgrip strength and mobility in children and adolescents with different types of osteogenesis imperfecta. Methods Cross-sectional study. Fifty selected subjects diagnosed with types I (n = 11), III (n = 21), and IV (n = 18), followed up at Brazilian reference center for osteogenesis imperfecta in the Midwest region, aged 2-21 years (9.2 ± 5.0), were enrolled in this study. Children and adolescents were evaluated for postural balance in the upright position with eyes-open and eyes-closed conditions, handgrip strength and the mobility domain (Pediatric Dysfunction Assessment Inventory). Data normality and difference between groups was verified. Results Handgrip strength was significantly lower in people with type III of osteogenesis imperfecta when compared to the osteogenesis imperfecta types I and IV, and to the age-specific reference data. Center of pressure length and mean velocity in the condition with eyes closed were worse compared to the open-eyes condition for children and adolescents with type I of osteogenesis imperfecta. There were worse results in the mobility domain for the participants classified with the most severe type of osteogenesis imperfecta. Conclusions It was observed that the severity of the osteogenesis imperfecta disease affected handgrip strength and locomotor function assessed by the mobility domain. Comparing osteogenesis imperfecta types, the higher the severity of osteogenesis imperfecta, the lower the handgrip strength. These results can contribute to new strategies of treatment focused on improving functional capacity and quality of life in people with osteogenesis imperfecta.