No abstract

Rat bite fever (RBF), a systemic infection of Streptobacillus moniliformis or Spirillum minus characterized by fever, arthralgias and petechial-purpuric rash on the extremities, carries a mortality rate of 7% to 10% if untreated. In Canada, one adult and two paediatric cases of RBF have been reported since 2000. In recent years, pet rats have become quite popular among children, placing them at an increased risk for RBF. Thus, paediatricians need to be more wary of the potential for RBF in their patients. In the present report, a culture-confirmed case of RBF and two additional cases of suspected infection are described.

BACKGROUND AND OBJECTIVES Puberty onset and development contribute substantially to adolescents’ bone mass and body composition. Our objective with this study was to examine the effects of gonadotropin-releasing hormone agonists (GnRHa) on these puberty-induced changes among youth with gender dysphoria (GD). METHODS Medical records of the endocrine diversity clinic in an academic children’s hospital were reviewed for youth with GD seen from January 2006 to April 2017 with at least 1 baseline dual-energy radiograph absorptiometry measurement. RESULTS At baseline, transgender females had lower lumbar spine (LS) and left total hip (LTH) areal bone mineral density (aBMD) and LS bone mineral apparent density (BMAD) z scores. Only 44.7% of transgender youth were vitamin D sufficient. Baseline vitamin D status was associated with LS, LTH aBMD, and LS BMAD z scores. Post-GnRHa assessments revealed a significant drop in LS and LTH aBMD z scores (transgender males and transgender females) without fractures and LS BMAD (transgender males), an increase in gynoid (fat percentage), and android (fat percentage) (transgender males and transgender females), and no changes in BMI z score. CONCLUSIONS GnRHa monotherapy negatively affected bone mineral density of youth with GD without evidence of fractures or changes in BMI z score. Transgender youth body fat redistribution (android versus gynoid) were in keeping with their affirmed gender. The majority of transgender youth had vitamin D insufficiency or deficiency with baseline status associated with bone mineral density. Vitamin D supplementation should be considered for all youth with GD.

We present the investigation and management of a premature, hypotensive neonate born after a pregnancy complicated by anhydramnios to highlight the impact of early and informed management for rare kidney disease. Vasopressin was used to successfully treat refractory hypotension and anuria in the neonate born at 27 weeks of gestation. Next generation sequencing of a targeted panel of genes was then performed in the neonate and parents. Subsequently, two compound heterozygous deletions leading to frameshift mutations were identified in the angiotensin 1-converting enzyme gene ACE; exon 5:c.820_821delAG (p.Arg274Glyfs*117) and exon24: c.3521delG (p.Gly1174Alafs*12), consistent with a diagnosis of renal tubular dysgenesis. In light of the molecular diagnosis, identification, and treatment of associated low aldosterone level resulted in further improvement in renal function and only mild residual chronic renal failure is present at 14 months of age. Truncating alterations in ACE most often result in fetal demise during gestation or in the first days of life and typically as a result of the Potter sequence. The premature delivery, and serendipitous early treatment with vasopressin, and then later fludrocortisone, resulted in an optimal outcome in an otherwise lethal condition.

Yunis-Varón syndrome (YVS) is an autosomal recessive disorder comprising skeletal anomalies, dysmorphism, global developmental delay and intracytoplasmic vacuolation in brain and other tissues. All hitherto-reported pathogenic variants affect FIG4, a lipid phosphatase involved in phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P] metabolism. FIG4 interacts with PIKfyve, a lipid kinase, via the adapter protein VAC14; all subunits of the resulting complex are essential for PtdIns(3,5)P synthesis in the endolysosomal membrane compartment. Here, we present the case of a female neonate with clinical features of YVS and normal FIG4 sequencing; exome sequencing identified biallelic rare coding variants in VAC14. Cultured patient fibroblasts exhibited a YVS-like vacuolation phenotype ameliorated in a dose-dependent fashion by ML-SA1, a pharmacological activator of the lysosomal PtdIns(3,5)P effector TRPML1. The patient developed a diffuse leukoencephalopathy with loss of the normal N-acetylaspartate spectrographic peak and presence of a large abnormal peak consistent with myoinositol. We report that VAC14 is a second gene for Yunis-Varón syndrome.

Huntingtin interacting protein 1 (HIP1) is an endocytic adaptor protein with clathrin assembly activity that binds to cytoplasmic proteins, such as F-actin, tubulin, and huntingtin (htt). To gain insight into diverse functions of HIP1, we characterized the male reproductive defect of HIP1(-/-) mice from 7 to 30 weeks of age. High levels of HIP1 protein were expressed in the testis of wild-type mice as seen by Western blots and as a reaction over Sertoli cells and elongating spermatids as visualized by immunocytochemistry. Accordingly, major structural abnormalities were evident in HIP1(-/-) mice with vacuolation of seminiferous tubules caused by an apparent loss of postmeiotic spermatids and a significant reduction in mean profile area. Remaining spermatids revealed deformations of their heads, flagella, and/or acrosomes. In some Sertoli cells, ectoplasmic specializations (ES) were absent or altered in appearance accounting for the presence of spherical germ cells in the epididymal lumen. Quantitative analyses of sperm counts from the cauda epididymidis demonstrated a significant decrease in HIP1(-/-) mice compared to wild-type littermates. In addition, computer-assisted sperm analyses indicated that velocities, amplitude of lateral head displacements (ALH), and numbers and percentages of sperm in the motile, rapid, and progressive categories were all significantly reduced in HIP1(-/-) mice, while the numbers and percentages of sperm in the static category were greatly increased. Taken together, these various abnormalities corroborate reduced fertility levels in HIP1(-/-) mice and suggest a role for HIP1 in stabilizing actin and microtubules, which are important cytoskeletal elements enabling normal spermatid and Sertoli cell morphology and function.

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Background/Aims: To evaluate factors contributing to the decision to initiate treatment with growth hormone (GH) in patients with Turner syndrome (TS). Methods: Data collected included ethnicity, parents’ education and work status, mid-parental height, age at diagnosis, karyotype, pubertal development, clinical severity score, bone age, height SDS and ages when GH was proposed and initiated. Results: GH was proposed to 59 of 72 patients >6 years (82%), and of these 46 (78%) accepted. Reasons for not proposing GH included late diagnosis, good growth and loss to follow-up. GH-treated and untreated girls differed by age at diagnosis (mean ± SD: 6.8 ± 4.7 vs. 4.3 ± 5.1 years; p = 0.04), TS-specific height SDS (0.08 ± 0.81 vs. 066 ± 0.87; p = 0.01) and spontaneous puberty (5/46 vs. 4/26, p = 0.024). Mean age at which it was suggested to begin GH was 9.2 ± 2.9 years. Reasons for parental refusal of GH were not related to reimbursement issues since GH treatment is covered fully by our insurance plan but included concern with other medical issues, mental health problems and fear of injections or unknown side effects. Conclusion: GH treatment was not acceptable to all patients with TS.