Alström Syndrome (ALMS) is an ultra-rare multisystem genetic disorder caused by autosomal recessive variants in the ALMS1 gene, which is located on chromosome 2p13. ALMS is a multisystem, progressive disease characterised by visual disturbance, hearing impairment, cardiomyopathy, childhood obesity, extreme insulin resistance, accelerated non-alcoholic fatty liver disease (NAFLD), renal dysfunction, respiratory disease, endocrine and urologic disorders. Clinical symptoms first appear in infancy with great variability in age of onset and severity. ALMS has an estimated incidence of 1 case per 1,000,000 live births and ethnically or geographically isolated populations have a higher-than-average frequency. The rarity and complexity of the syndrome and the lack of expertise can lead to delayed diagnosis, misdiagnosis and inadequate care. Multidisciplinary and multiprofessional teams of experts are essential for the management of patients with ALMS, as early diagnosis and intervention can slow the progression of multi-organ dysfunctions and improve patient quality of life. These guidelines are intended to define standard of care for patients suspected or diagnosed with ALMS of any age. All information contained in this document has originated from a systematic review of the literature and the experiences of the authors in their care of patients with ALMS. The Appraisal of Guidelines for Research & Evaluation (AGREE II) system was adopted for the development of the guidelines and for defining the related levels of evidence and strengths of recommendations. These guidelines are addressed to: a) specialist centres, other hospital-based medical teams and staffs involved with the care of ALMS patients, b) family physicians and other primary caregivers and c) patients and their families.

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Background The medium and long-term effects of severe SARS-CoV-2 infection on survivors are unknown. Here we studied the medium term effects of COVID-19 on survivors of severe disease. Methods This is a retrospective, case series of 200 patients hospitalised across three large Birmingham hospitals with severe-to-critical COVID-19 infection 4-7 months from disease-onset. Patients underwent comprehensive clinical, laboratory, imaging, lung function test, quality of life and cognitive assessments. Results At 4-7 months from disease-onset, 63.2% of patients experienced persistent breathlessness, 53.5% complained of significant fatigue, 37.5% reduced mobility and 36.8% pain. Serum markers of inflammation and organ injuries that persisted at hospital discharge had normalised on follow-up indicating no sustained immune response causing chronic maladaptive inflammation. Chest radiographs showed a complete resolution in 82.8%; and significantly improved or no change in 17.2%. Lung function test (LFT) revealed gas transfer abnormalities in 80.0% and spirometry in 37.6% patients. Patients with breathlessness had significantly high incidence of comorbidities, abnormal residual chest X-ray and LFT (p<0.01 to all). In all parameters assessed and persisting symptoms there was no statically significant difference between patients managed on hospital wards and on ITU groups. All patients reported a significantly reduced quality of life in all domains of the EQ-5D-5L quality of life measures. Conclusions and Relevance A significant proportion of COVID-19 with severe illness experience ongoing symptoms of breathlessness, fatigue, pain, reduced mobility, depression and reduced quality of life at 4-7 months from disease-onset. Symptomatic patients tend to have more residual CXR and LFT abnormalities.

In untreated hypogonadal men with KS, lumbar and femoral BMD was reduced, and femoral bone quality was impaired. Adiposity seemed to have a detrimental effect on lumbar bone microarchitecture, as indirectly evaluated by TBS. However, TRT failed to remedy these negative effects on bone.

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KS and HGAs should be considered as two distinct conditions.

Most KS patients had average fluid intelligence. PD prevalence was higher than in the general population. Testosterone was not correlated with fluid intelligence, personality traits or PD, but a reduction in marital distress was observed in treated patients. This could suggest that testosterone therapy can improve physical symptoms and this effect could also improve relationship abilities and wellness awareness.

Klinefelter syndrome has been associated with thyroid abnormalities, the genesis of which is not yet fully clear. The aim of this study was to evaluate thyroid function in Klinefelter syndrome subjects during the pubertal period. Chemiluminescent microparticle immunoassay was used to analyze Thyroid-Stimulating Hormone, fT3 and fT4 concentration in serum samples from 40 Klinefelter syndrome pubertal boys with classic 47,XXY karyotype and 157 healthy age-matched controls. 13 Klinefelter syndrome patients also underwent Thyrotropin-Releasing Hormone testing to evaluate hypothalamic-pituitary function. fT3 levels were significantly lower in Klinefelter syndrome patients than in age-matched controls (p < 0.001). No significant differences were found for Thyroid-Stimulating Hormone (p = 0.138) or fT4 (p = 0.274), but the serum levels of Klinefelter syndrome patients tended to cluster around the lower part of the reference range for the assay. Three of the thirteen Klinefelter syndrome patients undergoing the Thyrotropin-Releasing Hormone test had an adequate response, one had a prolonged response at 60 min and nine responded inadequately. This study demonstrated for the first time that pubertal Klinefelter syndrome patients have significantly lower fT3 serum levels than do healthy age-matched boys, whereas Thyroid-Stimulating Hormone and fT4 are normal, albeit at the lower end of the reference range. Most patients showed an inadequate/prolonged response to pituitary stimulation with Thyrotropin-Releasing Hormone. These findings suggest a combined form of both central and peripheral hypothyroidism in Klinefelter syndrome boys during pubertal development.