A Case of Congenital Dyserythropoeitic Anemia Type IV Caused by E325K Mutation in Erythroid Transcription Factor KLF1.

Congenital dyserythropoetic anemias (CDA) represent a heterogeneous group of inherited red cell disorders resulting in ineffective erythropoiesis. Several CDA variants have been identified. KLF1 is a transcription factor required for cell division in erythroid differentiation and maturation, and the switch from fetal to adult hemoglobin. Mutations in KLF1 gene can result in a wide range of phenotypes. This case illustrates the E325K mutation in KLF1 presenting with severe anemia in infancy, persistently elevated fetal hemoglobin, and progressive improvement with age. This case of CDA because of KLF1 mutation highlights the common features and expected disease course of CDA type IV.

Hb Grifton [α87(F8)His→Pro; HBA1: C.263A > C (or HBA2)] Causes Abnormal Pulse Oximetry Measurements.

An asymptomatic toddler and his mother consistently demonstrated low transcutaneous pulse oximetry (SpO2) measurements, discordant with normal arterial blood gas analyses while breathing room air. Previous evaluations by medical teams were unable to identify an etiology of their perceived hypoxia. Further investigation revealed that the boy carried an abnormal variant, Hb Grifton or α87(F8)His→Pro; HBA1: c.263A > C (or HBA2), discovered on newborn screening, which was not suspected as the underlying cause of his abnormal pulse oximetry readings until an inpatient admission to our hospital for asymptomatic "hypoxia," where he was found to share these same characteristics with his mother. We showed that a difference in light absorption between the oxygenated Hb Grifton variant and oxygenated Hb A resulted in erroneous pulse oximetry values. This phenomenon has previously been reported in a handful of other variant Hbs. Astute clinical suspicion, in conjunction with laboratory testing leading to correct diagnoses of variant Hbs, may prevent expensive work-ups and unnecessary medical treatments for asymptomatic patients falsely presumed to be hypoxemic based on low pulse oximetry measurements.

Multisystem Inflammatory Syndrome in a Previously Vaccinated Adolescent Female With Sickle Cell Disease.

Multisystem inflammatory syndrome in children (MIS-C) is a serious complication that is observed most commonly in pediatric patients following severe acute respiratory syndrome coronavirus 2 infections. However, the mechanism and predictors of disease are poorly understood. There are no prior reports of MIS-C among patients who have been fully vaccinated, and only a single case of MIS in an adult patient who had received his second shot just 4 days prior to symptom onset. Here, we present an adolescent with sickle cell disease who was fully vaccinated against severe acute respiratory syndrome coronavirus 2 and had no prior history of known or suspected infection, who presented in shock and was ultimately diagnosed with MIS-C. This case highlights the importance of clinical suspicion for MIS-C even when patients are fully vaccinated.

Small cell ovarian carcinoma: a rare, aggressive tumor masquerading as constipation in a teenager with a fatal outcome.

SUMMARY: A 16-year-old female presented with symptoms consistent with constipation with no constitutional symptoms. Multiple different laxatives were attempted over 4 months and were unsuccessful. This thin female developed an impressively distended, nonacute abdomen within a 2-week period. Histology demonstrated a stage IV small cell carcinoma of the ovary. Her disease initially responded to treatment, but ultimately she relapsed and failed to respond to 2 other chemotherapy combinations, which were based on limited success found in the literature. She ultimately passed away 13 months after the diagnosis, demonstrating the poor prognosis and rapid spread of this rare disease.

Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy.

We report germline missense mutations in ETV6 segregating with the dominant transmission of thrombocytopenia and hematologic malignancy in three unrelated kindreds, defining a new hereditary syndrome featuring thrombocytopenia with susceptibility to diverse hematologic neoplasms. Two variants, p.Arg369Gln and p.Arg399Cys, reside in the highly conserved ETS DNA-binding domain. The third variant, p.Pro214Leu, lies within the internal linker domain, which regulates DNA binding. These three amino acid sites correspond to hotspots for recurrent somatic mutation in malignancies. Functional studies show that the mutations abrogate DNA binding, alter subcellular localization, decrease transcriptional repression in a dominant-negative fashion and impair hematopoiesis. These familial genetic studies identify a central role for ETV6 in hematopoiesis and malignant transformation. The identification of germline predisposition to cytopenias and cancer informs the diagnosis and medical management of at-risk individuals.

Ewing's sarcoma family tumors mimicking primary central nervous system neoplasms.

Ewing's sarcoma family tumors (ESFTs) and embyronal tumors of the central nervous system are malignant primitive neuroectodermal tumors (PNETs) that can arise in the central nervous system, bones, or soft tissues. When ESFTs involve the central nervous system or nearby structures the diagnosis depends on cytogenetics and immunohistochemistry as these tumors can appear otherwise histologically identical to central PNETs. Correct diagnosis is essential as the treatment paradigms for both entities differ. We present two cases of isolated central nervous system presentations of ESFTs mimicking primary central nervous system neoplasms.