Metabolic Contributions to Pathobiology of Asthma.

Asthma is a heterogenous disorder driven by inflammatory mechanisms that result in multiple phenotypes. Given the complex nature of this condition, metabolomics is being used to delineate the pathobiology of asthma. Metabolomics is the study of metabolites in biology, which includes biofluids, cells, and tissues.

The past, present, and future of child growth monitoring: A review and primer for clinical genetics.

Child growth measurements are critical vital signs to track, with every individual child growth curve potentially revealing a story about a child's health and well-being. Simply put, every baby born requires basic building blocks to grow and thrive: proper nutrition, love and care, and medical health. To ensure that every child who is missing one of these vital aspects is identified, growth is traditionally measured at birth and each well-child visit.

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.

Context: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy.

Objective: To evaluate safety and efficacy of intranasal carbetocin in PWS.

Pediatric medical genetics house call: Telemedicine for the next generation of patients and providers.

In an era of increasing technology and interaction with the patient bedside, we explore the role of relocating the bedside from the hospital to the home using telemedicine. The COVID-19 pandemic pushed telemedicine from small and pilot programs to widespread practice at an unprecedented rate. With the rapid implementation of telemedicine, it is important to consider how to create a telehealth system that provides both good care for patients and families while maintaining an excellent education environment for trainees of all levels.

The natural history of type 2 Gaucher disease in the 21st century: A retrospective study.

Objective: To gather natural history data to better understand the changing course of type 2 Gaucher disease (GD2) in order to guide future interventional protocols.

Methods: A structured interview was conducted with parents of living or deceased patients with GD2. Retrospective information obtained included disease presentation, progression, medical and surgical history, medications, family history, management, complications, and cause of death, as well as the impact of disease on families.

Variation in cognitive function over time in Gaucher disease type 3.

Objective: To identify relevant efficacy parameters essential in designing clinical trials for brain-penetrant therapies for Gaucher disease, we evaluated cognitive function longitudinally in 34 patients with Gaucher disease type 3 seen at the NIH Clinical Center.

Methods: Individuals were tested with age-appropriate Wechsler Intelligence Scales administered between 1 and 18 times over 29 years. Variation in all IQ domains was not linear with time and was best characterized with the coefficient of variation (SD/mean) for each individual.

Five-parameter evaluation of dysphagia: A novel prognostic scale for assessing neurological decline in Gaucher disease type 2.

Background: Gaucher disease type 2 (GD2) is defined by acute neurological decline, failure to thrive, and early demise. Currently, there is no clear standard for evaluating, staging, and counseling regarding neurological decline in GD2. Due to the high prevalence of progressive dysphagia secondary to acute neurological involvement, we aimed to identify key components of swallow function which could serve as markers of disease progression in GD2.

Type 2 Gaucher disease in an infant despite a normal maternal glucocerebrosidase gene.

Gaucher disease (GD) is a recessively inherited autosomal lysosomal storage disease, the most severe of which is type 2, an acute neuronopathic form. We report an affected infant who inherited one mutant allele, Arg257Gln (c.887G>A; p.

The Spectrum of Neurological Manifestations Associated with Gaucher Disease.

Gaucher disease, the most common lysosomal storage disorder, is due to a deficiency in the enzyme glucocerebrosidase. This leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages, affecting the hematological, visceral, bone and neurologic systems. Gaucher disease is classified into three broad phenotypes based upon the presence or absence of neurological involvement: type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (subacute neuronopathic).

Induced pluripotent stem cell models of lysosomal storage disorders.

Induced pluripotent stem cells (iPSCs) have provided new opportunities to explore the cell biology and pathophysiology of human diseases, and the lysosomal storage disorder research community has been quick to adopt this technology. Patient-derived iPSC models have been generated for a number of lysosomal storage disorders, including Gaucher disease, Pompe disease, Fabry disease, metachromatic leukodystrophy, the neuronal ceroid lipofuscinoses, Niemann-Pick types A and C1, and several of the mucopolysaccharidoses. Here, we review the strategies employed for reprogramming and differentiation, as well as insights into disease etiology gleaned from the currently available models.

Cornelia de Lange syndrome: Correlation of brain MRI findings with behavioral assessment.

Neurobehavioral and developmental issues with a broad range of deficits are prominent features of Cornelia de Lange syndrome (CdLS), a disorder due to disruption of the cohesin protein complex. The etiologic relationship of these clinical findings to anatomic abnormalities on neuro-imaging studies has not, however, been established. Anatomic abnormalities in the brain and central nervous system specific to CdLS have been observed, including changes in the white matter, brainstem, and cerebellum.