The germline p53 activation syndrome: A new patient further refines the clinical phenotype.

The tumor suppressor p53 has well known roles in cancer development and germline cancer predisposition disorders, but increasing evidence supports the role of activation of this transcription factor in the pathogenesis of inherited bone marrow failure and chromosomal instability disorders. Here we report a patient with red cell aplasia, which was steroid responsive, as well as intellectual disability, seizures, microcephaly, short stature, cellular radiosensitivity, and normal telomere lengths, who had a germline heterozygous C-terminal frameshift variant in TP53 similar to others that activate the transcription factor. This is the third reported individual with a germline p53 activation syndrome, with several unique features that refine the clinical disease associated with these variants.

Hospital Use and Mortality in Transition-Aged Patients With Sickle Cell Disease.

Objectives: Childhood mortality in sickle cell disease (SCD) has decreased, but the transition period is associated with poor outcomes and higher mortality rates. We analyzed recent US hospitalizations and mortality trends in the transition-aged population and evaluated for differences between patients with and without SCD.

Methods: Nationwide Inpatient Sample database was used to analyze hospitalizations among individuals aged 16 to 24 years from 2003 to 2017.

Case Report: Post-Partum Complications of Deficiency Underscore a Need to Better Understand Primary Immunodeficiency Management During Pregnancy.

Nuclear factor κappa-B (NFκB) is a family of transcription factors involved in regulating inflammation and immunity. Mutations in the pathway are associated with primary immune defects and underlie the most common monogenic etiology of common variable immunodeficiency (CVID). However, little is known about how defects or primary immunodeficiency (PID) complicate pregnancy.

Expansion of the clinical phenotype of GALE deficiency.

Congenital disorders of glycosylation are a group of rare monogenic inborn errors of metabolism caused by defective glycoprotein and glycolipid glycan synthesis and attachment. Here, we present a patient with galactose epimerase deficiency, also known as GALE deficiency, accompanied by pancytopenia and immune dysregulation. She was first identified by an abnormal newborn screen for galactosemia with subsequent genetic evaluation due to pancytopenia and immune dysregulation.

Effective hemostasis in children with Von Willebrand factor defects undergoing adenotonsillar procedures.

Introduction: Children with low von Willebrand factor (VWF) activity or type 1 von Willebrand disease (VWD) have increased risk of bleeding after adenotonsillar procedures and the optimal perioperative management to minimize bleeding is unknown.

Aim: To report the effectiveness and safety of an institutional protocol in minimizing postoperative bleeding in children with type 1 VWD or low VWF activity.

Methods: We conducted a retrospective chart review in children with type 1 VWD or low VWF activity treated via an institutional protocol that utilizes repeated doses of Desmopressin acetate (DDAVP, 1-deamino 8-D arginine- vasopressin) or VWF concentrate, brief hospitalization for observation and extended use of oral epsilon aminocaproic acid (EACA).

Barriers to and Facilitators of Iron Therapy in Children with Iron Deficiency Anemia.

Objective: To characterize barriers to and facilitators of successful iron therapy in young children with iron deficiency anemia (IDA) from an in-depth parental perspective.

Study Design: Prospective, mixed methods study of children age 9 months to 4 years with a diagnosis of nutritional IDA by clinical history and laboratory criteria and their parents. Clinical data were obtained from the electronic health record.

A Critical Evaluation of Enoxaparin Dose Adjustment Guidelines in Children.

Objectives: The purposes of this study are to perform a large-scale evaluation of the standardized dosage adjustment nomogram recommended by the American College of Chest Physicians (CHEST) for the management of enoxaparin in hospitalized pediatric patients and to determine the necessity of routine and repeated anti-factor Xa (anti-Xa) levels.

Methods: A retrospective cohort study was designed, and charts were reviewed in a single tertiary care institution for all patients who received enoxaparin between October 1, 2010, through September 30, 2016. Patients were included if they were receiving treatment doses of enoxaparin according to the pediatric CHEST guidelines, had a subtherapeutic or supratherapeutic anti-Xa level drawn at 3.

Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features.

Shwachman-Diamond syndrome (SDS) (OMIM #260400) is a rare inherited bone marrow failure syndrome (IBMFS) that is primarily characterized by neutropenia and exocrine pancreatic insufficiency. Seventy-five to ninety percent of patients have compound heterozygous loss-of-function mutations in the Shwachman-Bodian-Diamond syndrome (sbds) gene. Using trio whole-exome sequencing (WES) in an sbds-negative SDS family and candidate gene sequencing in additional SBDS-negative SDS cases or molecularly undiagnosed IBMFS cases, we identified 3 independent patients, each of whom carried a de novo missense variant in srp54 (encoding signal recognition particle 54 kDa).

Population Pharmacokinetics of Enoxaparin in Pediatric Patients.

Background: There are no studies evaluating the pharmacokinetics of enoxaparin in the hospitalized pediatric patient population.

Objective: To characterize the pharmacokinetics of enoxaparin in pediatric patients.

Methods: A retrospective review of inpatients 1 to 18 years of age admitted to our institution who received enoxaparin with anti-factor Xa activity level monitoring was performed.

Enoxaparin Population Pharmacokinetics in the First Year of Life.

Aims: Enoxaparin dosing requirements in the first year of life can be highly variable. Characterization of pharmacokinetics in this patient population can assist in dosing.

Methods: Patients less than 1 year postnatal age who received enoxaparin and had an anti-factor Xa activity level drawn as inpatients were identified through the pharmacy database over a 5-year period.

Novel mechanisms of PIEZO1 dysfunction in hereditary xerocytosis.

Mutations in PIEZO1 are the primary cause of hereditary xerocytosis, a clinically heterogeneous, dominantly inherited disorder of erythrocyte dehydration. We used next-generation sequencing-based techniques to identify mutations in individuals from 9 kindreds referred with suspected hereditary xerocytosis (HX) and/or undiagnosed congenital hemolytic anemia. Mutations were primarily found in the highly conserved, COOH-terminal pore-region domain.

Population pharmacokinetics of human antithrombin concentrate in paediatric patients.

Aims: Antithrombin is increasingly used in paediatric patients, yet there are few age-specific pharmacokinetic data to guide dosing. We aimed to describe the pharmacokinetic profile of human (plasma-derived) antithrombin concentrate in paediatric patients.

Methods: A 5-year retrospective review was performed of patients <19 years of age admitted to our institution who received antithrombin concentrate, were not on mechanical circulatory support and had baseline (predose) and postdose plasma antithrombin activity levels available for analysis.

Pediatric Acquired von Willebrand Syndrome in Cardiopulmonary Disorders: Do Laboratory Abnormalities Predict Bleeding Risk?

There are conflicting reports on whether or not laboratory abnormalities in pediatric acquired von Willebrand syndrome (AVWS) predict bleeding manifestations in patients with cardiopulmonary disorders (CPD). We retrospectively reviewed charts of patients with AVWS and CPD (n=16) seen at Texas Children's Hospital from 2003 to 2012. The most common CPD were valve stenoses, ventricular septal defects, and pulmonary hypertension.

Assessment of an Electronic Intervention in Young Women with Heavy Menstrual Bleeding.

Unlabelled: STUDY OBJECTIVE, DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Bleeding disorders (BD) occur in up to 50% of adolescents with heavy menstrual bleeding (HMB). This presents unique challenges to health care providers because of the complexity of treating the condition and such complexity can result in difficulty with patients understanding basic information about their condition, limit communication with medical providers, and patient compliance. The aim of the study was to use an electronic approach to enhance patient compliance with medications used to treat their HMB, and to provide educational access to adolescents with BD.

Profound Vitamin B12 Deficiency in a 1-Year-Old Child in Botswana: A Call to Initiate Early Empiric Therapy.

Vitamin B12 deficiency is a rare diagnosis in young children. We present the case of a 1-year-old Zimbabwean child with profound anemia. Further testing revealed undetectable levels of vitamin B12 and positive intrinsic factor antibodies that were drawn after the initiation of empiric treatment with parenteral vitamin B12.

Thrombopoietin Measurement as a Key Component in the Evaluation of Pediatric Thrombocytosis.

JAK2, MPL, and CALR mutations, which underlie essential thrombocythemia (ET) in most adults, are infrequent in children. Consequently, additional tests are needed to confirm pediatric ET diagnoses. We report a child with suspected ET and normal JAK2, MPL, and CALR analyses.

The genomic landscape of juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 or CBL occur in 85% of patients, yet there are currently no risk stratification algorithms capable of predicting which patients will be refractory to conventional treatment and could therefore be candidates for experimental therapies. In addition, few molecular pathways aside from the RAS-MAPK pathway have been identified that could serve as the basis for such novel therapeutic strategies.

Antithrombin Concentrate Use in Children Receiving Unfractionated Heparin for Acute Thrombosis.

Objective: To characterize features of antithrombin concentrate (ATC) use in children receiving unfractionated heparin (UFH) therapy for acute thrombosis.

Study Design: All pediatric patients at Texas Children's Hospital who received ATC in the context of UFH therapy for acute thrombosis during February 2011 to May 2013 were analyzed.

Results: Fifty-one children received ATC during UFH therapy for acute thrombosis.

Oral Tranexamic Acid versus Combined Oral Contraceptives for Adolescent Heavy Menstrual Bleeding: A Pilot Study.

Study Objective: To compare the efficacy of oral tranexamic acid (TA) with combined oral contraceptives (COC) in reducing menstrual blood loss (MBL) and improving quality of life in adolescent heavy menstrual bleeding (HMB).

Design, Setting, And Participants: A prospective randomized crossover trial with 17 postmenarchal girls aged 21 years and younger with HMB who were seen at our institution.

Interventions: Patients were randomized to group A (TA arm) or group B (COC arm), each for 3 cycles, with crossover to the second arm after 1-month washout.

Hemostatic abnormalities in young females with heavy menstrual bleeding.

Objective: To study the prevalence of hemostatic abnormalities, including bleeding disorders and risk factors, in young females referred to a multidisciplinary clinic for evaluation of heavy menstrual bleeding (HMB).

Methods: Retrospective chart review was undertaken for 131 post-menarchal girls with HMB, 7 to 17 years of age, enrolled in the institutional 'Menorrhagia Data Registry' protocol. The diagnostic approach included: (1) complete blood count, prothrombin time, partial thromboplastin time, fibrinogen, von Willebrand panel (2) platelet aggregometry, specific clotting factor assay, fibrinolytic pathway analysis, and factor XIII level as needed.