Citations

Abstract Background In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. Methods Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. Results Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1,152 patients have been evaluated with an overall solve rate of 14.1% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. Conclusion Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.

Patient satisfaction (PS) surveying has become a commonly used measure of physician performance, but little is known about the impact on pediatricians. To investigate our hypothesis that PS surveys negatively impact pediatricians, we conducted a survey at an academic children’s medical center. Of 155 eligible physicians, 115 responded (response rate 74%). Two-thirds (68%) did not find the PS score report useful and 88% did not feel that PS scores accurately reflect the physician’s clinical ability. A third reported ordering tests, medications, or consultations due to pressure for higher PS scores. In addition, one-third agreed that PS surveys contribute to burnout and make it difficult to practice meaningful medicine. Overall, PS score reporting has a negative impact on pediatricians, especially those who are female, BIPOC (Black, Indigenous, and People of color), subspecialists, younger, and attended non-US medical schools. Further investigation into improved methods for providing feedback to pediatric physicians is warranted.

AbstractThe proper use of intravenous fluids has likely been responsible for saving more lives than any other group of substances. Proper use includes prescribing an appropriate electrolyte and carbohydrate solution, at a calculated rate or volume, for the right child, at the right time. Forming intravenous fluid plans for hospitalized children requires an understanding of water and electrolyte physiology in healthy children and how different pathology deviates from the norm. This review highlights fluid management in several disease types, including liver disease, diabetic ketoacidosis, syndrome of inappropriate antidiuretic hormone, diabetes insipidus, kidney disease, and intestinal failure as well as in those with nonphysiologic fluid losses. For each disease, the review discusses specific considerations, evaluations, and management strategies to consider when customizing intravenous fluid plans. Ultimately, all hospitalized children should receive an individualized fluid plan with recurrent evaluations and fluid modifications to provide optimal care.

AbstractBackgroundWe sought to evaluate the association between vitamin D deficiency and the severity of coronavirus disease 2019 (COVID‐19) infection.MethodsMultiple databases from 1 January 2019 to 3 December 2020 were searched for observational studies evaluating the association between vitamin D deficiency and severity of COVID‐19 infection. Independent reviewers selected studies and extracted data for the review. The main outcomes of interest were mortality, hospital admission, length of hospital stay and intensive care unit admission.ResultsSeventeen observational studies with 2756 patients were included in the analyses. Vitamin D deficiency was associated with significantly higher mortality (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.50–4.05; 12 studies; hazard ratio [HR]: 4.11, 95% CI: 2.40–7.04; 3 studies), higher rates of hospital admissions (OR: 2.18, 95% CI: 1.48–3.21; 3 studies) and longer hospital stays (0.52 days; 95% CI: 0.25–0.80; 2 studies) as compared to nonvitamin D deficient status. Subgroup analyses based on different cut‐offs for defining vitamin D deficiency, study geographic locations and latitude also showed similar trends.ConclusionsVitamin D deficiency is associated with greater severity of COVID‐19 infection. Further studies are warranted to determine if vitamin D supplementation can decrease the severity of COVID‐19.

Abstract Background: Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) is a rare condition of phosphate wasting due to variants in the SLC34A3 gene, encoding the sodium-phosphate cotransporter 2c (NaPi2c) at the brush border of proximal renal tubular cells (1). While labs are characterized by low serum phosphorus, high 1,25 dihydroxyvitamin D and inappropriately high levels of urine phosphate and calcium, the presenting symptoms can vary widely. Little remains known about specific phenotype-genotype correlations, especially in children. Clinical Cases: We report three new cases of HHRH in an unrelated 12 year-old male, 9 year-old female and 14 year-old male. All three patients were found to have low serum phosphorus for age (2.9-3.2 mg/dL), normocalcemia (9.4-9.9 mg/dL), low to low-normal parathyroid hormone (7-15 pg/mL), elevated 1,25 dihydroxyvitamin D (91-178 pg/mL), and hypercalciuria (4.5-7.6 mg/kg/day). Urine phosphorus was inappropriately elevated given the degree of their hypophosphatemia. Despite having similar lab findings, however, their clinical presentations were varied. The 12 year-old male presented with lower extremity pain, which was previously ascribed to patellofemoral pain syndrome. He had no history of renal symptoms, though a renal ultrasound later identified stones bilaterally. Conversely, the 9 year-old female and 14 year-old male presented with recurrent urinary stones and no bone symptoms. Genetic analyses identified 4 novel SLC34A3 gene mutations. Of interest, the 12 year-old male and 9 year-old female each shared a variant (c.575C-T (p.Ser192Leu)) despite having disparate symptoms. All three patients were treated with phosphorus supplementation and were advised to discontinue Vitamin D, if this had previously been prescribed. Conclusion: These three cases highlight the variability of presenting signs and symptoms among individuals with HHRH. Obtaining an accurate diagnosis is critical, as the addition of Vitamin D can seriously worsen symptoms in HHRH though it is a commonly used treatment for other disorders of phosphate wasting and bone demineralization. To aid in clinical decision making, we present a stepwise approach to the diagnosis of hypophosphatemic diseases. References: (1) Lorenz-Depiereux, B., Benet-Pages, A., Eckstein, G., Tenenbaum-Rakover, Y., Wagenstaller, J., Tiosano, D., Gershoni-Baruch, R., Albers, N., Lichtner, P., Schnabel, D., Hochberg, Z., Strom, T. Hereditary Hypophosphatemic Rickets with Hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. Am. J. Hum. Genetic. 2006;78:193-201.

AbstractBackgroundDiabetes is a risk factor for poor COVID‐19 outcomes, but pediatric patients with type 1 diabetes are poorly represented in current studies.MethodsT1D Exchange coordinated a US type 1 diabetes COVID‐19 registry. Forty‐six diabetes centers submitted pediatric cases for patients with laboratory confirmed COVID‐19. Associations between clinical factors and hospitalization were tested with Fisher's Exact Test. Logistic regression was used to calculate odds ratios for hospitalization.ResultsData from 266 patients with previously established type 1 diabetes aged <19 years with COVID‐19 were reported. Diabetic ketoacidosis (DKA) was the most common adverse outcome (n = 44, 72% of hospitalized patients). There were four hospitalizations for severe hypoglycemia, three hospitalizations requiring respiratory support (one of whom was intubated and mechanically ventilated), one case of multisystem inflammatory syndrome in children, and 10 patients who were hospitalized for reasons unrelated to COVID‐19 or diabetes. Hospitalized patients (n = 61) were more likely than nonhospitalized patients (n = 205) to have minority race/ethnicity (67% vs 39%, P < 0.001), public insurance (64% vs 41%, P < 0.001), higher A1c (11% [97 mmol/mol] vs 8.2% [66 mmol/mol], P < 0.001), and lower insulin pump and lower continuous glucose monitoring use (26% vs 54%, P < 0.001; 39% vs 75%, P < 0.001). Age and gender were not associated with risk of hospitalization. Higher A1c was significantly associated with hospitalization, with an odds ratio of 1.56 (1.34‐1.84) after adjusting for age, gender, insurance, and race/ethnicity.ConclusionsHigher A1c remained the only predictor for hospitalization with COVID‐19. Diabetic ketoacidosis is the primary concern among this group.