Gonadal Hormone Substitution in People with Prader-Labhart-Willi Syndrome: An International Prader-Willi Syndrome Organisation Survey.

BACKGROUND: Prader-Labhart-Willi syndrome (PWS) is a rare genetic disorder characterized by intellectual disability, behavioural problems, hypothalamic dysfunction, and specific dysmorphisms. Hypothalamic dysfunction causes growth hormone deficiency, dysregulation of energy balance, and hypogonadism. Although hypogonadism is prevalent in PWS, there are no clear guidelines for diagnosis and treatment. In particular, gonadal hormone substitution is a matter of debate due to concerns associated with the potentially induced aggressive behaviour, foremost in males, by sex steroids. METHODS: In 2019, a workshop dedicated to hypogonadism was held prior to the 10th International PWS Organization Conference. In this context, we designed a questionnaire to assess "the current standard of care" of hypogonadism in children and adults with PWS, which was sent out to physicians caring for people with PWS worldwide. RESULTS: Responses were received from a total of 24 centres located in 19 countries. Participating centres treat a total number of at least 1,000 children and adults with PWS. Responses showed limited consensus on who should be treated or at what age treatment should commence. Remarkably, very few behavioural problems were attributed to hormone substitution. CONCLUSION: Based on our findings, we make recommendations to progress the knowledge on hypogonadism in PWS and improve daily practice.

Contemporary height, weight and body mass index references for children aged 0 to adulthood in Switzerland compared to the Prader reference, WHO and neighbouring countries.

Background: In 2011, WHO growth curves replaced those of Prader and colleagues (First Zurich longitudinal study) in Switzerland.Aim: To present contemporary height-, weight- and body mass index (BMI)-for-age references reflecting children's growth in modern Switzerland.Subjects and methods: Cross-sectional sample comprising 30,141 boys and girls aged 0-20 years measured between 2012 and 2019. Height, weight and BMI reference curves were created using the LMS method. Derived percentiles were compared with those of Prader, WHO and neighbouring countries.Results: Growth in the first 5 years is almost identical with Prader curves. Thereafter children are taller, yet their final height is only about 1 cm higher. Today's children, in particular boys, are considerably heavier. In comparison with WHO growth references, Swiss children are taller from the second year until adulthood; the WHO 3rd percentiles lie about 4 cm below those of our updated references. Weight and BMI median percentiles from our sample are similar to those of WHO and higher than the Prader curves. However, the course of the 97th BMI percentile WHO curves extends well below the 97th percentile of the updated Swiss curves.Conclusion: This study provides contemporary reference data for assessing individual growth based on height, weight and BMI of Swiss children.

A novel DAX-1 (NR0B1) mutation in a boy with X-linked adrenal hypoplasia congenita.

BACKGROUND: X-linked adrenal hypoplasia congenita (AHC) is caused by mutations in DAX-1 (NR0B1) playing a key role in adrenal and reproductive development. CASE PRESENTATION: Herein we report a 2.5-year-old boy who presented with acute adrenal failure. Family history revealed unexplained death in three brothers of the patient's mother during infancy. Molecular analysis of the DAX-1 gene revealed the presence of a novel hemizygous mutation, c.870C>A in exon 1, leading to the formation of a premature stop codon. The same mutation was identified in the patient's mother. The truncated mutant protein is most likely misfolded, sequestered in the endoplasmic reticulum and therefore cannot bind to and activate its target DNA sequences in the nucleus. CONCLUSIONS: DAX-1 mutation must be considered when diagnosis of primary adrenocortical insufficiency is made, especially if there is a history of unexplained death of maternal male relatives.

The Aldosterone/Renin Ratio as a Diagnostic Tool for the Diagnosis of Primary Hypoaldosteronism in Newborns and Infants.

BACKGROUND/AIMS: Primary hypoaldosteronism is a rare inborn disorder with life-threatening symptoms in newborns and infants due to an aldosterone synthase defect. Diagnosis is often difficult as the plasma aldosterone concentration (PAC) can remain within the normal range and thus lead to misinterpretation and delayed initiation of life-saving therapy. We aimed to test the eligibility of the PAC/plasma renin concentration (PRC) ratio as a tool for the diagnosis of primary hypoaldosteronism in newborns and infants. Meth ods: Data of 9 patients aged 15 days to 12 months at the time of diagnosis were collected. The diagnosis of primary hypoaldosteronism was based on clinical and laboratory findings over a period of 12 years in 3 different centers in Switzerland. To enable a valid comparison, the values of PAC and PRC were correlated to reference methods. RESULTS: In 6 patients, the PAC/PRC ratio could be determined and showed constantly decreased values <1 (pmol/l)/(mU/l). In 2 patients, renin was noted as plasma renin activity (PRA). PAC/PRA ratios were also clearly decreased. The diagnosis was subsequently genetically confirmed in 8 patients. CONCLUSION: A PAC/PRC ratio <1 pmol/mU and a PAC/PRA ratio <28 (pmol/l)/(ng/ml × h) are reliable tools to identify primary hypoaldosteronism in newborns and infants and help to diagnose this life-threatening disease faster.

Apheresis affects bone and mineral metabolism.

BACKGROUND: Apheresis is a procedure to selectively obtain blood components. For the collection process citrate is routinely used. It inhibits coagulation by binding to ionized calcium and leads to metabolic alkalosis. OBJECTIVE: Whether regular apheresis affects bone and mineral metabolism is unknown. The intention of this study was to investigate 1) the acute effects of apheresis on acid-base balance, bone and mineral metabolism and 2) to compare bone mineral density (BMD) at the lumbar spine and hip of donors to matched control subjects. DESIGN: In this open, observational, single-center, cross-sectional study we enrolled 102 regular plasma and thrombocyte donors to pursue objective 1) and compared those to 102 matched controls (CTR) for objective 2). RESULTS: Platelet donation led to significant decreases in serum ionized calcium (-17%) and phosphate (-18%), to marked increases in base excess (57%) and PTH levels (192%) during apheresis. Baseline biochemical comparisons between donors and CTR revealed significantly lower values for donors for serum calcium, albumin, and 25-hydroxyvitamin D levels. Mean Z-score at the lumbar spine adjusted for BMI, average physical activity and daily calcium intake was lower for donors (-0.28+/-0.11) when compared to CTR subjects (0.06+/-0.11, P<0.05). Total and neck femoral BMD was also lower in the donor group, however, this difference was not significant. CONCLUSIONS: Exposure to citrate during the apheresis procedure acutely affects mineral and bone metabolism. Regular donations of blood components compromised BMD at the lumbar spine. If confirmed, strategies to prevent long-term effects on bone need to be formulated.