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The various mutations taking place in the PPIB genes that lead to the onset of osteogenesis imperfecta (OI) disorder are discussed. The results prove that a dysfunctional complex is more likely to lead to OI, in comparison with the lack of a single proline residue.

Objectives X-Linked hypophosphataemic rickets (XLH) is a rare multi-systemic disease of mineral homeostasis that has a prominent skeletal phenotype. The aim of this study was to describe additional comorbidities in XLH patients compared with general population controls. Methods The Clinical Practice Research Datalink (CPRD) GOLD was used to identify a cohort of XLH patients (1995–2016), along with a non-XLH cohort matched (1 : 4) on age, sex and GP practice. Using the CALIBER portal, phenotyping algorithms were used to identify the first diagnosis (and associated age) of 273 comorbid conditions during patient follow-up. Fifteen major disease categories were used and the proportion of patients having ≥1 diagnosis was compared between cohorts for each category and condition. Main analyses were repeated according to the Index of Multiple Deprivation (IMD). Results There were 64 and 256 patients in the XLH and non-XLH cohorts, respectively. There was increased prevalence of endocrine [OR 3.46 (95% CI: 1.44, 8.31)] and neurological [OR 3.01 (95% CI: 1.41, 6.44)] disorders among XLH patients. Across all specific comorbidities, four were at least twice as likely to be present in XLH cases, but only depression met the Bonferroni threshold: OR 2.95 (95% CI: 1.47, 5.92). Distribution of IMD among XLH cases indicated greater deprivation than the general population. Conclusion We describe a higher risk of mental illness in XLH patients compared with matched controls, and greater than expected deprivation. These findings may have implications for clinical practice guidelines and decisions around health and social care provision for these patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Klinefelter’s syndrome is characterized by progressive testicular failure causing aspermatogenesis and androgen deficiency. Klinefelter patients classically have complete male sex differentiation, and genital anomalies are generally not recognized as associated features of the syndrome. Methods: We reviewed the cases of Klinefelter’s syndrome with genitalia abnormalities from the Cambridge Disorders of Sex Development Database, and also reviewed previous case reports of genital anomalies associated with Klinefelter’s syndrome and its variants. Results: We present seven Klinefelter patients with abnormalities of the genitalia, ranging from mild anomalies (chordee) to moderate undervirilisation (bifid scrotum and perineal hypospadias). Two cases were true hermaphrodites with karyotypes 47,XXY and 47,XXY/46,XX respectively. Though androgen insensitivity has been postulated previously as a possible pathogenic mechanism, we demonstrated normal androgen binding in 3 cases in which this was studied. Review of other case reports revealed a range of mild-to-severe abnormalities as well as cases reported as sex reversal, testicular feminization, and true hermaphroditism. Conclusion: Genital anomalies are not commonly observed in Klinefelter’s syndrome. However, it is important to acknowledge the association, and recognize Klinefelter’s syndrome as one of the causes of abnormal genitalia at birth. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: X-linked hypophosphatemia (XLH) is a rare multisystemic disease with a prominent musculoskeletal phenotype. We aim here to improve understanding of the prevalence of XLH across the life course and of overall survival among people with XLH., Methods: This was a population-based cohort study using a large primary care database in the United Kingdom (UK) from 1995 to 2016. XLH cases were matched by age, gender, and practice to up to 4 controls. Trends in prevalence over the study period were estimated (stratified by age) and survival among cases was compared with that of controls., Findings: From 522 potential cases, 122 (23.4%) were scored as at least possible XLH, while 62 (11.9%) were classified as highly likely or likely (conservative definition). In main analyses, prevalence (95% CI) increased from 3.1 (1.5-6.7) per million in 1995-1999 to 14.0 (10.8-18.1) per million in 2012-2016. Corresponding estimates using the conservative definition were 3.0 (1.4-6.5) to 8.1 (5.8-11.4). Nine (7.4%) of the possible cases died during follow-up, at median age of 64 years. Fourteen (2.9%) of the controls died at median age of 72.5 years. Mortality was significantly increased in those with possible XLH compared with controls (hazard ratio [HR] 2.93; 95% CI, 1.24-6.91). Likewise, among those with likely or highly likely XLH (HR 6.65; 1.44-30.72)., Conclusions: We provide conservative estimates of the prevalence of XLH in children and adults within the UK. There was an unexpected increase in mortality in later life, which may have implications for other fibroblast growth factor 23-related disorders., (© Endocrine Society 2019.)

Reduction of bone density and its associated morbidity is recognized in young adults with beta-thalassaemia major, but the aetiology is not clear. This study used dual X-ray absorptiometry (DXA) to look at bone mineral apparent density (BMAD) in children and young adults with thalassaemia in a predominantly Asian population, in the context of sexual maturation. Fifty-five patients were scanned (mean age 13.8 years, range 5.9-37.5) and BMAD z-scores were calculated using normal data from locally recruited control subjects. Eighteen patients had undergone bone marrow transplantation (BMT) and the remainder were on a transfusion/chelation regimen. BMAD z-scores ranged from -3.3-1.6 with a mean of -0.92. No difference in BMAD was found between those patients treated conventionally and those who had undergone BMT. When comparing mean BMAD z-score according to sexual maturation, there was a highly significant difference (P < 0.0001) between those whose pubertal maturation was age appropriate (mean z-score -0.22), when compared with those who had disordered puberty (mean z-score -1.82). We have shown that failure to progress normally through puberty is highly significant in the failure of adequate bone mineralization and achievement of peak bone mass in thalassaemic patients. The management of these patients should therefore be pro-active to anticipate problems and facilitate normal sexual maturation.