A Novel Variant in NR5A1 Presenting as 46,XY Difference of Sex Development.

Differences of sex development (DSDs) are a spectrum of congenital clinical conditions involving the development of gonadal, chromosomal, and anatomical sex. The physical presentation provides incomplete clues because underlying etiologies may present with similar findings. We describe an 8-year-old boy from the Dominican Republic originally diagnosed with congenital adrenal hyperplasia (CAH). He was prescribed oral hydrocortisone and fludrocortisone, with irregular adherence. During infancy, he had human chorionic gonadotropin injections to stimulate phallic growth. After migrating to the United States, medications became depleted but without adrenal crisis. Laboratory testing with high-dose adrenocorticotropin stimulation study ruled out CAH. Careful examination noted an underdeveloped bifid scrotum, bilaterally undescended testicles, a 2-cm phallus, severe penoscrotal hypospadias, and chordee. Subsequently, he had a 2-stage bilateral orchiopexy and surgical repair of penoscrotal hypospadias and chordee. Genetic testing for 46,XY DSD revealed a novel, dominant, heterozygous, likely pathogenic variant (c.102 + 1G > C) in the NR5A1 gene associated with severe phenotype of undervirilized male. This case illustrates the crucial role of molecular genetic testing for the diagnosis of 46,XY DSDs and a novel NR5A1 gene variant.

El impacto de la pandemia del COVID-19 en la educación médica: adaptabilidad y experiencia con enseñanza a distancia de la Sociedad Médica Peruano Americana

La pandemia del COVID-19 tuvo un impacto significativo en el cuidado y la educación médicos en el Perú. En respuesta, la Sociedad Médica Peruano Americana (PAMS), una organización médica benéfica con sede en los EE.UU., adoptó sus misiones médicas y educativas en Perú usando estrategias virtuales. Desarrollamos colaboración con varias facultades de medicina y la Asociación Peruana de Facultades de Medicina (ASPEFAM) y ofrecimos un panel de veinte y cuatro miembros para brindar conferencias y seminarios multidisciplinarios en español. Hicimos 19 seminarios, incluyendo temas relacionados y no relacionados al COVID-19, que en los últimos dos años atrajo a 14 489 participantes de 23 países. Ellas fueron la base de 20 publicaciones en revistas médicas peruanas. Nuestro concurso de investigaciones clínicas y nuestro proyecto piloto de mentoría de investigación fueron recibidos positivamente. La pandemia del COVID-19 tuvo un efecto positivo en la misión educativa de PAMS en Perú.

The COVID-19 pandemic had a significant impact on medical care and medical education in Peru. In response, the Peruvian American Medical Society (PAMS), a charitable medical organization based in the USA, pursued its medical and educational missions in Peru by adopting virtual learning technology. We developed closer collaborative relationships with several medical schools and the Peruvian Association of Medical Schools (ASPEFAM) while offering a faculty panel of twenty-four members to provide lectures and multidisciplinary webinars in Spanish. We conducted 19 webinars including COVID -19 and non-COVID-19 related topics that over the last two years attracted 14,489 participants from 23 countries. They were the foundation for twenty publications in Peruvian medical journals. Our clinical investigations competition was positively received as was our pilot project on research mentorship. The COVID -19 pandemic had a positive effect on the educational mission of PAMS in Peru.

The Coronavirus Disease 2019 Pandemic is Associated with a Substantial Rise in Frequency and Severity of Presentation of Youth-Onset Type 2 Diabetes.

OBJECTIVES: To evaluate the frequency and severity of new cases of youth-onset type 2 diabetes in the US during the first year of the pandemic compared with the mean of the previous 2 years. STUDY DESIGN: Multicenter (n = 24 centers), hospital-based, retrospective chart review. Youth aged ≤21 years with newly diagnosed type 2 diabetes between March 2018 and February 2021, body mass index ≥85th percentile, and negative pancreatic autoantibodies were included. Demographic and clinical data, including case numbers and frequency of metabolic decompensation, were compared between groups. RESULTS: A total of 3113 youth (mean [SD] 14.4 [2.4] years, 50.5% female, 40.4% Hispanic, 32.7% Black, 14.5% non-Hispanic White) were assessed. New cases of type 2 diabetes increased by 77.2% in the year during the pandemic (n = 1463) compared with the mean of the previous 2 years, 2019 (n = 886) and 2018 (n = 765). The likelihood of presenting with metabolic decompensation and severe diabetic ketoacidosis also increased significantly during the pandemic. CONCLUSIONS: The burden of newly diagnosed youth-onset type 2 diabetes increased significantly during the coronavirus disease 2019 pandemic, resulting in enormous strain on pediatric diabetes health care providers, patients, and families. Whether the increase was caused by coronavirus disease 2019 infection, or just associated with environmental changes and stressors during the pandemic is unclear. Further studies are needed to determine whether this rise is limited to the US and whether it will persist over time.

A centennial review of discoveries and advances in diabetes: Children and youth.

Diabetes is an increasingly common chronic metabolic disorder in children worldwide. The discovery of insulin in 1921 resulted in unprecedented advancements that improved the lives of children and youth with diabetes. The purpose of this article is to review the history of diabetes in children and youth over the last century and its implications for future developments in the field. We identified 68 relevant events between 1921 and 2021 through literature review and survey of pediatric endocrinologists. Basic research milestones led to the discovery of insulin and other regulatory hormones, established the normal physiology of carbohydrate metabolism and pathophysiology of diabetes, and provided insight into strategies for diabetes prevention. While landmark clinical studies were initially focused on adult diabetes populations, later studies assessed etiologic factors in birth cohort studies, evaluated technology use among children with diabetes, and investigated pharmacologic management of youth type 2 diabetes. Technological innovations culminated in the introduction of continuous glucose monitoring that enabled semi-automated insulin delivery systems. Finally, professional organizations collaborated with patient groups to advocate for the needs of children with diabetes and their families. Together, these advances transformed type 1 diabetes from a terminal illness to a manageable disease with near-normal life expectancy and increased our knowledge of type 2 diabetes and other forms of diabetes in the pediatric population. However, disparities in access to insulin, diabetes technology, education, and care support remain and disproportionately impact minority youth and communities with less resources. The overarching goal of diabetes management remains promoting a high quality of life and improving glycemic management without undermining the psychological health of children and youth living with diabetes.

Do Mindfulness Interventions Improve Obesity Rates in Children and Adolescents: A Review of the Evidence.

Mindfulness interventions have shown promise in improving self-regulation, depression, anxiety, and stress levels across all ages. Obesity rates in children are rising worldwide. It has been postulated that through improvements in self-regulation with mindfulness interventions, obesity rates can be improved in children and adolescents. In this review, we attempt to explain how mindfulness interventions may impact obesity rates and obesity-related complications and give the current state of evidence for the following mindfulness interventions: Mindful Eating, Mindfulness-Based Stress Reduction, Yoga, Spirituality, and Dialectical Behavior Therapy.

Use of glucagon-like peptide-1 receptor agonists for pediatric patients with obesity and diabetes: The providers' perspectives.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been widely used in adults with Type 2 diabetes (T2D) and obesity. We sought to evaluate the experience of pediatric endocrinology providers with GLP-1RA and factors that guide them on whether and how to prescribe these medications. METHODS: We surveyed the members of the Pediatric Endocrine Society regarding the use of GLP-1RA in their practice. RESULTS: The respondents (n = 102) were predominantly from academic centers (84%) and 75%reported using GLP-1RA in pediatric patients, mostly to treat T2D and obesity. Patient tolerance for the medication was reported to be the driving factor determining the duration of treatment. Gastrointestinal side effects were observed more commonly than local reactions or elevation of pancreatic enzymes. Lack of clinical experience was reported to be a major barrier for prescribing GLP-1RA, particularly among those with more than 5 years of clinical experience. Finally, liraglutide was used more often (93%) than other GLP-1RA. CONCLUSIONS: The use of GLP-1RA has increased in pediatric patients. Recent Food and Drug Administration approval of liraglutide for pediatric obesity will likely further increase its prescription rate. Providers should be vigilant about side effects and adjust the doses of GLP-1RA accordingly. More efforts should be made by professional societies to educate pediatric endocrinology providers about the proper use of GLP-1RA and enhance their confidence in prescribing these medications.

De Novo and Inherited Pathogenic Variants in KDM3B Cause Intellectual Disability, Short Stature, and Facial Dysmorphism.

By using exome sequencing and a gene matching approach, we identified de novo and inherited pathogenic variants in KDM3B in 14 unrelated individuals and three affected parents with varying degrees of intellectual disability (ID) or developmental delay (DD) and short stature. The individuals share additional phenotypic features that include feeding difficulties in infancy, joint hypermobility, and characteristic facial features such as a wide mouth, a pointed chin, long ears, and a low columella. Notably, two individuals developed cancer, acute myeloid leukemia and Hodgkin lymphoma, in childhood. KDM3B encodes for a histone demethylase and is involved in H3K9 demethylation, a crucial part of chromatin modification required for transcriptional regulation. We identified missense and truncating variants, suggesting that KDM3B haploinsufficiency is the underlying mechanism for this syndrome. By using a hybrid facial-recognition model, we show that individuals with a pathogenic variant in KDM3B have a facial gestalt, and that they show significant facial similarity compared to control individuals with ID. In conclusion, pathogenic variants in KDM3B cause a syndrome characterized by ID, short stature, and facial dysmorphism.

Challenging diagnosis of congenital hyperinsulinism in two infants of diabetic mothers with rare pathogenic KCNJ11 and HNF4A gene variants.

BACKGROUND: Congenital hyperinsulinism (CHI) is the leading cause of persistent hypoglycemia in infants. The infants of diabetic mothers (IDMs) very frequently present with neonatal hypoglycemia associated to transient hyperinsulinism however the incidence of CHI in IDMs is unknown. CASE PRESENTATION: Here we report 2 cases of CHI where the diagnoses were challenged and delayed because both patients were infants of diabetic mothers (IDMs) and had concomitant complicated medical conditions. Case 1 was heterozygous for a likely pathogenic variant in KCNJ11(p.Arg206Cys), and Case 2 was heterozygous for a pathogenic HNF4A variant, (p.Arg267Cys). HNF4A-associated CHI is very rare, and this particular case had a clinical phenotype quite different from that of previously described HNF4A-CHI cases. CONCLUSIONS: This case series is one of few reports in the medical literature describing two IDMs with persistent recurrent hypoglycemia secondary to CHI, and a different clinical phenotype for HNF4A-associated CHI. IDMs typically present with transient hyperinsulinism lasting no more than 2-3 days. Since being an IDM does not exclude CHI, this diagnosis should always be considered as the mostly likely etiology if neonatal hypoglycemia persists longer than the described time frame and genetic testing for CHI confirmation is highly suggested.

[National congenital hypothyroidism screening in Peru: a broken program]. / Tamizaje nacional unificado de hipotiroidismo congénito en el Perú: un programa inexistente.

Congenital hypothyroidism (CH) is the most important cause of preventable mental retardation. The prevalence of CH varies by geographic region, race and ethnicity. In the countries of the Northern hemisphere, the prevalence has been reported as 1:4,000 live newborns. The prevalence is remarkably different among the countries of Latin America not only because of their different races and ethnicities but also because of the heterogeneous social-economic development. The prevalence of CH in 1984 in Peru was reported as 1:1250. In 2007, the reported incidence by the Instituto Nacional Materno Perinatal was 1:1638. A recent retrospective study performed by the Instituto Nacional de Salud del Niño in Lima, Peru described the average age of diagnosis of CH as 5,9 months +/- 5,28. This late age of CH diagnosis certainly suggests the poor efficiency of the current neonatal CH screening programs in Peru. Every Peruvian infant deserves a timely newborn screening and treatment for CH. The Peruvian government is responsible for ensuring this mandatory goal is achieved promptly.

Tamizaje nacional unificado de hipotiroidismo congénito en el Perú: un programa inexistente / National congenital hypothyroidism screening in Peru: a broken program

El hipotiroidismo congénito (HC) es la principal causa prevenible de retardo mental. La prevalencia de HC varía de acuerdo con la región geográfica y la población racial. En el hemisferio norte, la incidencia es 1:4000 recién nacidos vivos. En Latinoamérica, la incidencia varía debido a la heterogeneidad racial/étnica y al nivel de desarrollo. En el Perú, un estudio realizado en 1984 describió esta prevalencia como 1:1250. En el 2007, esta prevalencia fue reportada como 1:1638 por el Instituto Nacional Materno Perinatal. Un reciente estudio del Instituto Nacional de Salud del Niño durante 1995û2005, describió la edad promedio de diagnóstico de HC como 5,9 meses +/- 5,28. Esta tardía edad de diagnóstico sugiere la poca eficiencia de los actuales programas de tamizaje. Todo niño peruano tiene derecho a recibir diagnóstico oportuno y tratamiento de HC y es el Estado Peruano, el responsable principal de asegurar que esta meta se cumpla...

Congenital hypothyroidism (CH) is the most important cause of preventable mental retardation. The prevalence of CH varies by geographic region, race and ethnicity. In the countries of the Northern hemisphere, the prevalence has been reported as 1:4,000 live newborns. The prevalence is remarkably different among the countries of Latin America not only because of their different races and ethnicities but also because of the heterogeneous social-economic development. The prevalence of CH in 1984 in Peru was reported as 1:1250. In 2007, the reported incidence by the Instituto Nacional Materno Perinatal was 1:1638. A recent retrospective study performed by the Instituto Nacional de Salud del Niño in Lima, Peru described the average age of diagnosis of CH as 5,9 months +/- 5,28. This late age of CH diagnosis certainly suggests the poor efficiency of the current neonatal CH screening programs in Peru. Every Peruvian infant deserves a timely newborn screening and treatment for CH. The Peruvian government is responsible for ensuring this mandatory goal is achieved promptly...

Gender Bias in U.S. Pediatric Growth Hormone Treatment.

Growth hormone (GH) treatment of idiopathic short stature (ISS), defined as height <-2.25 standard deviations (SD), is approved by U.S. FDA. This study determined the gender-specific prevalence of height <-2.25 SD in a pediatric primary care population, and compared it to demographics of U.S. pediatric GH recipients. Data were extracted from health records of all patients age 0.5-20 years with ≥ 1 recorded height measurement in 28 regional primary care practices and from the four U.S. GH registries. Height <-2.25 SD was modeled by multivariable logistic regression against gender and other characteristics. Of the 189,280 subjects, 2073 (1.1%) had height <-2.25 SD. No gender differences in prevalence of height <-2.25 SD or distribution of height Z-scores were found. In contrast, males comprised 74% of GH recipients for ISS and 66% for all indications. Short stature was associated (P < 0.0001) with history of prematurity, race/ethnicity, age and Medicaid insurance, and inversely related (P < 0.0001) with BMI Z-score. In conclusion, males outnumbered females almost 3:1 for ISS and 2:1 for all indications in U.S. pediatric GH registries despite no gender difference in height <-2.25 SD in a large primary care population. Treatment and/or referral bias was the likely cause of male predominance among GH recipients.

Tap or bottled water: drinking preferences among urban minority children and adolescents.

The last decade has seen an increasing trend in consumer preference of bottled water over tap water. Little is known what type of water children and adolescents prefer for drinking and what their parents think of their community tap water. The study objective was to assess drinking water preferences, perceptions of the qualities of tap water and bottled water, and fluoride knowledge in an urban pediatric population. We conducted an anonymous survey of a convenience sample of caretakers of children and adolescents at an urban clinic regarding their preferences for tap or bottled water, their perceptions of the quality of tap and bottled water and their knowledge of fluoride. Of the 208 participants (79% African American, 9% Latino), 59% drank tap water, 80% bottled water. Only 17% drank tap water exclusively, 38% drank bottled water exclusively, 42% drank both. We found no significant differences in water preferences across age groups, from infancy to adulthood, or among ethnic groups. Ratings for taste, clarity, purity and safety were significantly higher for bottled water than tap water (P < 0.001). Only 24% were aware of fluoride in drinking water. We conclude bottled water was preferred over tap water in an urban minority pediatric population. Perceptions of the qualities of water seemed to drive drinking preferences. Public health strategies are needed to increase public awareness of the impact of bottled water consumption on oral health, household budgets and the environment.