ABSTRACT.We describe the complex presentation of a patient with renal medullary carcinoma, a newly described entity primarily affecting young patients with sickle cell trait. Renal medullary carcinoma is an aggressive, rapidly destructive tumor associated with a delayed diagnosis and a poor outcome. The most common presenting signs and symptoms include hematuria, abdominal or flank pain, and weight loss. Sickle cell trait as the sole cause of hematuria in young black patients is a diagnosis of exclusion. Hemoglobin electrophoresis, intravenous pyelography, and computed tomography scans should be the minimal studies performed in young black patients with hematuria. Pediatrics 1999;103(2). URL: http://www.pediatrics.org/cgi/content/full/103/2/e22; sickle cell trait, hematuria, renal medullary carcinoma, renal tumors.ABBREVIATION. CT, computed tomography. R enal tumors represent 7.8% of all pediatric malignancies in the United States.1 Most of these are Wilms' tumors affecting children Ͻ5 years of age. Recently, a new entity, renal medullary carcinoma, has been described in young people, including children, with sickle cell disorders.2 Many of the reported cases have been diagnostic challenges with poor prognoses. It is unclear whether earlier diagnosis and earlier treatment will result in a better prognosis, but awareness of this newly described entity is most important. We describe an 18-year-old female with sickle cell trait who was diagnosed with renal medullary carcinoma after a complex presentation. CASE PRESENTATIONW.B. was an 18-year-old black female with known sickle trait, who was in good health until 6 months before admission when she developed swelling and stiffness in her metacarpophalangeal and knee joints. Her initial evaluation was significant for microscopic hematuria and a positive antinuclear antibody test with a titer of 1:640 and a diffuse pattern. She was treated with oral salicylates and naproxen sodium in the 2 months before this admission, but she took them infrequently.Two months after her initial presentation, she developed daily nausea and bilious vomiting, resulting in a 20-lb weight loss (15% of total body weight) over a 3-week period. She sought medical care when she developed worsening right-sided flank pain and gross hematuria. She was admitted with a presumptive diagnosis of papillary necrosis. Her review of systems at the time of admission was also significant for fever, sharp intermittent periumbilical pain, midline back pain, right scapular pain, urinary frequency with nocturia, gross hematuria with clots, loose stools, and night sweats. She denied dysuria. The patient had a past medical history of hypertension of unknown cause (untreated), epistaxis, easy bruising, and vaginal yeast infections. She had been sexually active for 4 years.At the time of physical examination, the patient was well developed and appeared well nourished despite her weight loss. She was bent over, secondary to pain. Her vital signs were significant for a blood pressure of 158/87 mm Hg. She had two café ...

for Practice Non-invasive hemoglobin testing with the Masimo Pronto device may be a useful screening tool for anemia in infants that avoids invasive testing.

CDAR (ClinicalTrials.gov Identifier: NCT02964494), a registry for patients with Congenital Dyserythropoietic Anemia (CDA) in North America, has been created with the goal to provide a longitudinal database and associated biorepository to facilitate natural history studies and research on the molecular pathways involved in the pathogenesis of CDAs. A 1 y.o. female patient with non-immune hemolytic anemia with suboptimal reticulocytosis, requiring frequent transfusions, and with the pathologic diagnosis of CDA was enrolled in CDAR. Her father had a similar phenotypical presentation in early childhood and underwent splenectomy at 3 years of age. Since then, he has rarely required transfusions but he continues to have a mild anemia at baseline with characteristics of hemolysis and with suboptimal reticulocytosis; at the time of enrollment, he had hemoglobin of 9.3 g/dL with absolute reticulocyte count of 115 x 106 cells/µl. Next Generation sequencing and deletion/duplication assay for the known CDA-associated genes (CDAN1, C15ORF41, SEC23B, KIF23, GATA1) identified no mutations. Whole-exome sequencing for the patient and her parents (family-trio design) revealed a novel PRDX2 missense variant (c.154C>T; p.Pro52Ser) present in heterozygous state in both proband and her father; no mutation in this gene was present in the asymptomatic mother. In silico prediction programs suggest that this variant is probably damaging and deleterious, causing a non-conservative substitution of a phylogenetically highly-conserved amino acid (down to Baker's yeast), and located in an enzymatically active protein domain, adjacent to the active Cys51, with the potential to change its conformation. Peroxiredoxin II is highly expressed during terminal erythropoiesis and is one of the most abundant proteins after hemoglobin in erythroblasts and mature erythrocytes. It is an antioxidant enzyme that reduces the reactive oxygen species (ROS), like hydrogen peroxide and alkyl hydroperoxides readily produced within the erythroid cells due to the presence of heme iron and oxygen. In addition, PRDX2 has been implicated in intracellular signaling, cellular proliferation and differentiation, and as a regulator of iron homeostasis. PRDX2-/- mice were found to have hemolytic anemia with evidence of oxidative damage of the erythrocyte proteins resulting to decreased red blood cell (RBC) survival. The aim of this work is to validate the pathogenetic role of the PRDX2 variant found in this family as the molecular cause of this dominantly-inherited CDA and further investigate the role of PRDX2 in human terminal erythropoiesis. Central review of the patient's bone marrow aspirate and biopsy slides, according to the CDAR protocol, revealed erythroid hyperplasia with dyserythropoiesis, including megaloblastoid changes, nuclear lobation and fragmentation, and binucleated erythroblasts (less than 10%), compatible with atypical CDA. There were rare erythroids with cytoplasmic bridging but no nuclear bridges. Review of the peripheral blood smear showed significant poikilocytosis, mild polychromasia, and the presence of blister and ghost cells reminiscent of G6PD deficiency, pointing to RBC damage by oxidative stress. Induced pluripotent stem cells (iPSCs) and EBV-immortalized lymphocytes were generated from the patients' peripheral blood mononuclear cells after informed consent per CDAR protocol, to allow further in vitro studies of the peroxiredoxin II-deficiency. Flow cytometry confirmed significantly increased ROS in the patients' derived versus control EBV-immortalized lymphocytes as well as in the reticulocytes and mature erythrocytes of the proband and her father, indicating that their PRDX2 variant is causing loss-of-function of the enzyme and increased oxidative stress. Further work is ongoing to explore the mechanisms of pathogenicity of peroxiredoxin II deficiency towards human dyserythropoiesis and decreased erythrocyte lifespan. To our knowledge, this is the first case of anemia described in humans associated with PRDX2 mutation implicating this gene as a novel candidate gene for atypical, dominantly-inherited CDA. Disclosures No relevant conflicts of interest to declare.

Based on national data, 1/3rd of all Honduran children under age 5 suffer from anemia. No studies to date have mapped the prevalence of anemia within rural Honduras. Objectives were to 1) determine and map the prevalence of anemia within children ages 6 to 60 months and 2) determine socioeconomic, growth, nutrition, and health factors associated with anemia. Randomized household surveys were conducted in collaboration with the Honduran Ministry of Health. Hemoglobin was obtained from 851 children living within 16 health centers. Altitude, latitude, and longitude were obtained at each household using a handheld global positioning system. Anemia was defined as hemoglobin < 11.0 g/dL (altitude adjusted). Overall prevalence of anemia was 29.8%. Anemia prevalence in one health center was <20%, 20–30% in 7 health centers, 31–40% in 6 health centers, and 40–50% in 2 health centers. Mapping data shows the prevalence of anemia in each health center. Risk factors associated with anemia included living at elevations >5,000 feet, (p=.012), mother was anemic (p=.005), weight‐for‐age z‐scores < −2 (p=.049), clinic distance > 1hour from home (p=.004), consumed meat < 2 times per month (p=.029), > 7 people living in household (p=.019), house constructed from material other than brick (p=.030), mother attended school < 3 years (p=.015), and child breastfed > 24 months (p=.000). By targeting health centers at highest risk for anemia, the Honduran Ministry of Heath can use this data to implement prevention measures as a means of reducing childhood morbidity. Supported by Henry M. Jackson Foundation for Advancement of Military Medicine.

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