ALBERT

Description: Background: Iron deficiency, even without a diagnosis of anemia, can be neurodevelopmentally dangerous in pediatric populations. Oral iron supplementation has been the treatment of choice but is associated with poor adherence for several reasons including metallic taste of the tablets, gastric irritation, severe constipation, and daily dosing for several weeks. Intravenous iron has been safely used in adult populations for iron supplementation, but has less commonly been used in pediatric populations. It is hypothesized that pediatric patients with iron deficiency anemia (IDA) who receive intravenous iron infusions will show normalization of hematologic parameters. Methods: EMR of patients aged 1-21 who received at least one intravenous iron infusion at Cooper University Hospital between 2016 and January 2019 were reviewed for retrospective data collection. Pre-infusion lab values including Hgb, MCV, RBCs and RDW were compared to post-infusion values to determine if values normalized after intravenous iron infusion. Patient demographics including ethnicity, cause of IDA, prior oral iron treatments, and adverse effects of oral and IV iron were analyzed. Results: There were 33 subjects in this study. The average age of the subjects was 12.8 (+/- 5.1) years of age and 79% were female. The most prevalent indication for IV iron was menorrhagia (55%), while GI issues were 18% and insufficient diet accounted for 27%. The mean baseline HGB was 8.3 (+/- 1.7) while the mean final HGB increased to 11.5 (+/- 1.4) (p

Description: Introduction: Hereditary Spherocytosis (HS) is the most common red cell membrane disorder. 25-30% of cases involve the SPTB gene which encodes for β-Spectrin, a protein that maintains red blood cell shape. Heterozygous variants in SPTB are associated with autosomal dominant HS and elliptocytosis. While genetic testing is not routinely done to confirm HS, it is useful in atypical presentations. Case Description: A 1 week old male presented to the pediatric hematology/oncology clinic for anemia. He was born late preterm and had a history of hyperbilirubinemia requiring phototherapy, failure to thrive, and developmental delay. On examination, he was noted to have hypotonia. There was no known family history of hematologic problems. Based on this constellation of signs and symptoms, he had a comprehensive hematologic and genetic workup. On lab evaluation, his peripheral blood smear showed normocytic normochromic red blood cells with some spherocytes, significant polychromasia, normal WBC and normal platelet morphology. His newborn screen was normal, direct coombs' negative, osmotic fragility test was positive, and protein band 3 reduction was abnormal. His abdominal ultrasound was normal. Whole exome sequencing with variant segregation analysis was significant for heterozygosity of the p.Q1034X variant of the SPTB gene. This variant in the SPTB gene has not been previously reported. Discussion: We found a novel, de novo variant in an infant with HS through whole exome sequencing. This variant is predicted to cause loss of normal protein function either through protein truncation or non-mediated mRNA decay resulting in fragile red blood cells. While neither parent was found to carry this mutation, germline mosaicism should not be excluded. Physicians should be aware that prenatal diagnosis is available to address the risk of recurrence in future pregnancies. References: 1. Ankyrin-1 mutations are a major cause of dominant and recessive hereditary spherocytosis Stefan Eber-Jennifer Gonzalez-Marcia Lux-Alphonse Scarpa-William Tse-Marion Dornwell-Jutta Herbers-Wilfried Kugler-Refik Ozcan-Arnulf Pekrun-Patrick Gallagher-Werner Schroter-Bernard Forget-Samuel Lux - Nature Genetics - 1996 2. Characterization of the underlying molecular defect in hereditary spherocytosis associated with spectrin deficiency. H Hassoun-JN Vassiliadis-J Murray-PR Njolstad-JJ Rogus-SK Ballas-F Schaffer-P Jarolim-V Brabec-J Palek - Blood - 1997 3. The Complexity of Genotype-Phenotype Correlations in Hereditary Spherocytosis: A Cohort of 95 Patients Vuren-Annelies & Zwaag-Bert & Huisjes-Rick & Lak-Nathalie & Bierings-M.B. & Gerritsen-Egbert & van Beers-Eduard & Bartels-Marije & Van Wijk-Richard - HemaSphere - 2019 4. Hereditary spherocytosis with spectrin deficiency due to an unstable truncated beta spectrin. H Hassoun-JN Vassiliadis-J Murray-SJ Yi-M Hanspal-CA Johnson CA-J Palek - Blood - 1996 5. LL Peters- Semin Hematol-2018 6. Red cell membrane: past, present, and future Narla Mohandas-Patrick Gallagher - Blood - 2008 7. Spectrum of Ankyrin Mutations in Hereditary Spherocytosis: A Case Report and Review of the Literature Yeping Luo-Zhuoying Li-Lihua Huang-Jing Tian-Menglong Xiong-Zuocheng Yang - Acta Haematologica - 2018 Figure: A map of all the pathogenic mutations found on the protein structures of ankyrin-1, a-spectrin, b-spectrin and band 3. Figure Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Gestational Alloimmune Liver Disease (GALD) is a rare disease characterized by subacute fetal liver injury and often accompanied by hepatic and extrahepatic iron deposition. Findings include hypoglycemia, coagulopathy, hypoalbuminemia, elevated serum ferritin, elevated alpha-fetoprotein, and ascites. Extrahepatic hemosiderin deposition is often seen in salivary glands. Previously, the mortality rate was close to 80% with all patients needing liver transplantation. With maternal IVIG treatment and changes in neonatal treatment, there is now less than 20% mortality with infrequent need for liver transplantation. Diagnosis of GALD is typically done on a postmortem analysis. Case Description: A term female infant was born via scheduled c-section to a 32 year old G2P1000 mother who had been receiving weekly IVIG during this pregnancy due to the death of her first child at 4 days of life. Autopsy of that female baby demonstrated extensive neuropathological changes, liver steatosis, iron depletion, and ascites, consistent with GALD. Following delivery of our current patient, there was an elevated alpha-fetoprotein (greater than 80,000), decreased fibrinogen, and coagulopathy with peak international normalized ratio of 1.6. The patient received fresh frozen plasma and IVIG on day of life 1 with improvement of these levels. Complete blood count, liver function tests, and ammonia were within normal limits. An MRI of the liver demonstrated normal size, morphology, and normal iron levels based on T2 relaxometry. A buccal biopsy did not demonstrate extrahepatic iron deposition. MRI of the brain showed significant stenosis of the right transverse and sigmoid sinus relating to dural venous sinus thrombosis. There was no evidence of parenchymal infarction and no evidence of iron deposition. At this time, enoxaparin was initiated. The patient was discharged home on day of life nine on enoxaparin therapy. Discussion: There are few reported cases of patients with GALD, especially after maternal IVIG treatment. This case report exemplifies the effect of antenatal IVIG infusions during subsequent pregnancies in women with a history of GALD in prior children. This effect is protective, evidenced by lack of liver injury noted in this patient. This supports the use of immunotherapy during pregnancy to prevent recurrence of alloimmune injury. References: 1. Is exchange transfusion a possible treatment for neonatal hemochromatosis? Giuseppina Timpani-Francesca Foti-Antonino Nicolò-Pier Nicotina-Emanuele Nicastro-Raffaele Iorio - Journal of Hepatology - 2007 2. Medical and surgical treatment of neonatal hemochromatosis: Single center experience-Thomas Heffron-Todd Pillen-David Welch-Massimo Asolati-Gregory Smallwood-Phil Hagedorn-Carlos Fasola-David Solis-John Rodrigues-Jill Depaolo-James Spivey-Enrique Martinez-Stuart Henry-Rene Romero - Pediatric Transplantation - 2007 3. Neonatal Hemochromatosis: A Congenital Alloimmune Hepatitis - Peter Whitington - Seminars in Liver Disease - 2007 4. Neonatal hemochromatosis: The importance of early recognition of liver failure Pankaj Vohra-Cindy Haller-Sukru Emre-Margret Magid-Ian Holzman-Ming Ye-Elizaveta Iofel-Benjamin Shneider - The Journal of Pediatrics - 2000 5. Neonatal Liver Cirrhosis Without Iron Overload Caused by Gestational Alloimmune Liver Disease. Debray-François Guillaume de Halleux- Virginie Guidi-Ornella Detrembleur-Nancy Gaillez-Stéphanie Rausin-Léon Goyens-Philippe Pan-Xiaomin Whitington Peter-Pediatrics-2012 6. Neonatal Liver Failure and Congenital Cirrhosis due to Gestational Alloimmune Liver Disease: A Case Report and Literature Review Oscar Roos Mariano da Rocha Carolina-Renata Rostirola Guedes- Carlos Oscar Kieling- Marina Rossato Adami- Carlos Thadeu Schmidt Cerski- Sandra Maria Conçalvez Vieria - Hindawi - 2017 Image: (A) MRI liver showing normal appearance without evidence of hemochromatosis (B) MRI brain showing no evidence of iron deposition within the brain parenchyma (C) MRV head showing right transverse and sigmoid venous sinus thrombosis Figure Disclosures No relevant conflicts of interest to declare.