Paroxysmal hyperthermia, dysautonomia and rhabdomyolysis in a patient with Lesch-Nyhan syndrome.

Lesch-Nyhan syndrome is an x-linked genetic disorder of purine metabolism that results in the overproduction of uric acid and neurologic deficits manifesting as intellectual disability, dystonia, other movement disorders and self-mutilation. We describe a 12-year-old patient with a history of Lesch-Nyhan syndrome, G6PD deficiency and central diabetes insipidus and multiple admissions for fever, acute kidney injury and transaminitis in the setting of rhabdomyolysis. The patient's temperature dysregulation and dysautonomia is likely attributable to abnormal neurotransmitter release, particularly that of dopamine, in the central nervous system. Our patient presented similarly to that of a patient with neuroleptic malignant syndrome (NMS), with symptoms including altered mental status, fever, dysautonomia and renal failure, and laboratory findings including elevated serum creatinine kinase, leukocytosis, transaminitis, hypernatremia and metabolic acidosis. Similar to NMS, disruption of dopamine neurotransmission results in dysregulated sympathetic activity and hyperthermia.

Social Determinants of Health and the Role of Routine Pediatric Care in a Medically Complex Toddler.

CASE: Late on a Friday afternoon, a new family presents to your practice for urgent care. They come with their youngest child Mai, a 2-year-old girl, who, although born in the United States at 36 weeks gestation, has resided in Laos with her grandparents for the past 16 months. Your triage nurse tells you that she has a fever and was found to have profound anemia while at the WIC (Special Supplemental Nutrition Program for Women, Infants, and Children) office earlier today.On walking into the room, you describe Mai as "listless" and "sickly." Her vitals were notable for fever (102°F), tachycardia (140 beats per minute), and tachypnea (35 breaths per minute). On physical examination, she was grunting with a systolic ejection murmur and without hepatosplenomegaly. Laboratory test results revealed hemoglobin of 2.2 g/dL, hematocrit of 12%, mean corpuscular volume of 50 fL, red cell distribution width of 27%, reticulocyte count of 3%, ferritin of <2 ng/mL, iron of 15 µg/dL, total iron binding count of 420 µg/dL, white blood cell count of 13.5 K/µL, and platelets of 605 K/µL. Her evaluation was consistent with severe iron deficiency anemia (IDA), which was further supported by reported restrictive diet and excessive cow milk intake of 35 ounces daily. She was admitted to the Pediatric Intensive Care Unit in high-output cardiac failure and was slowly transfused with 15 mL/kg of packed red blood cells over 2 days with careful monitoring. Once stabilized, she was transferred to the inpatient floor for further nutritional evaluation and supplementation. Additional workup, including hemoglobin electrophoresis, fecal occult blood test, celiac studies, and stool parasite testing were normal. The clinical picture was consistent with a viral infection in the setting of profound IDA and malnutrition.Although her clinical status had improved, she remained inpatient for nutritional optimization. Her height was at the 54th percentile (z-score: 0.11), weight was at the first percentile (z-score: -2.25), and body mass index was below the first percentile (z-score: -3.18), diagnostic of severe protein-calorie malnutrition. She was evaluated by an interdisciplinary growth and nutrition team, received multivitamin and mineral supplements, and was monitored for refeeding syndrome. She was noted to be "difficult to engage," "resistant to new faces," and made little progress on expanding her dietary choices. Concerns about a possible diagnosis of autism spectrum disorder were raised by her treating team. What would you do next? REFERENCE: 1. Bouma S. Diagnosing pediatric malnutrition: paradigm shifts of etiology-related definitions and appraisal of the indicators. Nutr Clin Pract. 2017;32:52-67.

A Primary Care-Based Quality Improvement Initiative to Increase Identification of Pediatric International Travelers.

Children who travel internationally to visit friends and relatives (VFRs) are at risk for travel-related illness, but underuse pretravel health services. Although primary care clinics can identify travelers and address pretravel health needs, to date, there are few published reports on effective primary care-based pretravel interventions. We developed a quality improvement initiative to increase traveler identification at a primary care clinic serving families that frequently travel to VFRs. Interventions included a screening question asked at all clinic visits, provider and staff training, travel fliers, and health recommendation sheets for families. Interventions were implemented during 2017 and 2018 peak travel seasons. Travel visit rates and characteristics during the intervention period were compared with pre-intervention baseline periods (April-August, 2015-16). Surveys with providers were conducted to assess disruptiveness of the interventions, and rates of duplicate travel visits were assessed. A total of 738 unique travel events were identified during peak travel seasons from 2015 to 2018, encompassing travel to 29 countries across five continents. Overall, there were 428 unique travel events (3.0% of all clinic visits) during peak seasons 2017-18, compared with 310 unique travel events (2.2% of all clinic visits) during peak seasons 2015-16 (rate ratio 1.34 [95% CI: 1.16-1.56], P < 0.001). None of the 18 healthcare providers or staff surveyed found new travel screening processes to be disruptive or bothersome. Implementation of a primary care-based multimodal travel screening and education initiative was associated with a significantly increased rate of travel visits.

Applying rigor and reproducibility standards to assay donor-derived cell-free DNA as a non-invasive method for detection of acute rejection and graft injury after heart transplantation.

BACKGROUND: Use of new genomic techniques in clinical settings requires that such methods are rigorous and reproducible. Previous studies have shown that quantitation of donor-derived cell-free DNA (%ddcfDNA) by unbiased shotgun sequencing is a sensitive, non-invasive marker of acute rejection after heart transplantation. The primary goal of this study was to assess the reproducibility of %ddcfDNA measurements across technical replicates, manual vs automated platforms, and rejection phenotypes in distinct patient cohorts. METHODS: After developing and validating the %ddcfDNA assay, we subjected the method to a rigorous test of its reproducibility. We measured %ddcfDNA in technical replicates performed by 2 independent laboratories and verified the reproducibility of %ddcfDNA patterns of 2 rejection phenotypes: acute cellular rejection and antibody-mediated rejection in distinct patient cohorts. RESULTS: We observed strong concordance of technical-replicate %ddcfDNA measurements across 2 independent laboratories (slope = 1.02, R2 > 0.99, p < 10-6), as well as across manual and automated platforms (slope = 0.80, R2 = 0.92, p < 0.001). The %ddcfDNA measurements in distinct heart transplant cohorts had similar baselines and error rates. The %ddcfDNA temporal patterns associated with rejection phenotypes were similar in both patient cohorts; however, the quantity of ddcfDNA was significantly higher in samples with severe vs mild histologic rejection grade (2.73% vs 0.14%, respectively; p < 0.001). CONCLUSIONS: The %ddcfDNA assay is precise and reproducible across laboratories and in samples from 2 distinct types of heart transplant rejection. These findings pave the way for larger studies to assess the clinical utility of %ddcfDNA as a marker of acute rejection after heart transplantation.