In humans, low peak bone mass is a significant risk factor for osteoporosis. We report that LRP5, encoding the low-density lipoprotein receptor-related protein 5, affects bone mass accrual during growth. Mutations in LRP5 cause the autosomal recessive disorder osteoporosis-pseudoglioma syndrome (OPPG). We find that OPPG carriers have reduced bone mass when compared to age- and gender-matched controls. We demonstrate LRP5 expression by osteoblasts in situ and show that LRP5 can transduce Wnt signaling in vitro via the canonical pathway. We further show that a mutant-secreted form of LRP5 can reduce bone thickness in mouse calvarial explant cultures. These data indicate that Wnt-mediated signaling via LRP5 affects bone accrual during growth and is important for the establishment of peak bone mass.

Cyclic vomiting syndrome (CVS) is a disorder noted for its unique intensity of vomiting, repeated emergency department visits and hospitalizations, and reduced quality of life. It is often misdiagnosed due to the unappreciated pattern of recurrence and lack of confirmatory testing. Because no accepted approach to management has been established, the task force was charged to develop a report on diagnosis and treatment of CVS based upon a review of the medical literature and expert opinion. The key issues addressed were the diagnostic criteria, the appropriate evaluation, the prophylactic therapy, and the therapy of acute attacks. The recommended diagnostic approach is to avoid "shotgun" testing and instead to use a strategy of targeted testing that varies with the presence of 4 red flags: abdominal signs (eg, bilious vomiting, tenderness), triggering events (eg, fasting, high protein meal), abnormal neurological examination (eg, altered mental status, papilledema), and progressive worsening or a changing pattern of vomiting episodes. Therapeutic recommendations include lifestyle changes, prophylactic therapy (eg, cyproheptadine in children 5 years or younger and amitriptyline for those older than 5), and acute therapy (eg, 5-hydroxytryptamine receptor agonists, termed triptans herein, as abortive therapy, and 10% dextrose and ondansetron for those requiring intravenous hydration). This document represents the official recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition for the diagnosis and treatment of CVS in children and adolescents.

Cyclic vomiting syndrome (CVS) was initially described in children but can occur in all age groups. Cyclic vomiting syndrome is increasingly recognized in adults. However, the lack of awareness of CVS in adults has led to small numbers of diagnosed patients and a paucity of published data on the causes, diagnosis and management of CVS in adults. This article is a state-of-knowledge overview on CVS in adults and is intended to provide a framework for management and further investigations into CVS in adults.

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Introduction-Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is a disorder of oxidation of long chain fat, and can present as cardiomyopathy or fasting intolerance in the first months to years of life, or as myopathy in later childhood to adulthood. Expanded newborn screening has identified a relatively high incidence of this disorder (1:31,500), but there is a dearth of evidence-based outcomes data to guide the development of clinical practice protocols. This consensus protocol is intended to assist clinicians in the diagnosis and management of screenpositive newborns for VLCAD deficiency until evidence-based guidelines are available.