Glucose-6-Phosphate Dehydrogenase Deficiency, Chlorproguanil-Dapsone with Artesunate and Post-treatment Haemolysis in African children treated for uncomplicated Malaria

Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The objective of the study was to assess whether CDA treatment and G6PD deficiency are risk factors for a post-treatment haemoglobin drop in African children<5 years of age with uncomplicated malaria

The Number of X Chromosomes Causes Sex Differences in Adiposity in Mice

Sexual dimorphism in body weight, fat distribution, and metabolic disease has been attributed largely to differential effects of male and female gonadal hormones. Here, we report that the number of X chromosomes within cells also contributes to these sex differences. We employed a unique mouse model, known as the “four core genotypes,” to distinguish between effects of gonadal sex (testes or ovaries) and sex chromosomes (XX or XY). With this model, we produced gonadal male and female mice carrying XX or XY sex chromosome complements. Mice were gonadectomized to remove the acute effects of gonadal hormones and to uncover effects of sex chromosome complement on obesity. Mice with XX sex chromosomes (relative to XY), regardless of their type of gonad, had up to 2-fold increased adiposity and greater food intake during daylight hours, when mice are normally inactive. Mice with two X chromosomes also had accelerated weight gain on a high fat diet and developed fatty liver and elevated lipid and insulin levels. Further genetic studies with mice carrying XO and XXY chromosome complements revealed that the differences between XX and XY mice are attributable to dosage of the X chromosome, rather than effects of the Y chromosome. A subset of genes that escape X chromosome inactivation exhibited higher expression levels in adipose tissue and liver of XX compared to XY mice, and may contribute to the sex differences in obesity. Overall, our study is the first to identify sex chromosome complement, a factor distinguishing all male and female cells, as a cause of sex differences in obesity and metabolism

Different karyotypes, same disease?

High grade aneuploidies of the sex chromosomes (HGA) presenting with a male phenotype comprise a vast and heterogenous group of very rare conditions, once considered as “variants” of Klinefelter syndrome (KS). This association with KS was mainly based on the presence of at least one supernumerary X chromosome, high stature and hypergonadotropic hypogonadism with severe testicular hypotrophy. However, many of the shared features show elevated severity in HGA compared to KS, while many others are unique to HGA. Different karyotypes arise from mechanisms peculiar to each HGA syndrome. Age at diagnosis ranges from pre-natal to early adulthood and an increased mortality ratio has been reported in these patients, mostly from respiratory diseases and congenital abnormalities. Among physical features the most common include: facial dysmorphisms, radioulnar synostosis, clinodactyly, impaired genital development (e.g. micropenis, cryptorchidism) renal dysplasia, cardiac malformations and taurodontism. Almost all patients show learning disabilities and intellectual deficits are common, with full scale IQs as low as 20-40, with verbal performances being the most affected. Behaviorally attention deficit-hyperactivity disorder (ADHD) and autism spectrum disorders are common, and patients’ temper can range from shyness to aggressiveness. Androgen replacement therapy is often necessary to start or complete pubertal development and is effective in ameliorating neuropsychiatric symptoms to some extent. Fertility is severely impaired, with all HGA patients being azoospermic and is often not a concern given the concurrent intellectual disability, although access to assisted reproduction techniques can be evaluated on a case-by-case basis