Clinical insights from Wolman disease: Evaluating infantile hepatosplenomegaly.

There is a broad differential diagnosis of infantile hepatosplenomegaly, with some etiologies being debilitating and treatable. A structured approach to history, examination, and laboratory and radiographic findings is important in diagnosis. Herein, we present a case of Wolman disease presenting as hepatosplenomegaly in an infant. This case details important learning points to help distinguish the diagnosis of Wolman disease from other conditions with overlapping clinical features, such as hemophagocytic lymphohistiocytosis (HLH). The advent of enzyme replacement therapy has dramatically changed the natural history of Wolman disease, and this child showed remarkable improvement with treatment. This child was later found to have extensive adenopathy with retroperitoneal lymph node biopsy demonstrating diffuse infiltration by lipid-laden macrophages, fatty deposits, cholesterol crystals, and calcifications. Similar to the collection of characteristic cells in other lysosomal storage disorders, we postulate that this is characteristic of underlying Wolman disease. We conclude with a summary of learning points from this presentation on infantile hepatosplenomegaly, pertinent to the geneticist, pediatrician, and pediatric subspecialists.

Severe Acute Respiratory Syndrome Coronavirus-2 Lambda Variant Collected from a Child from Arkansas and Sequenced.

An eleven-year-old tested positive for SARS-CoV-2 Lambda variant. Sequencing was performed on the Oxford Nanopore and the Illumina NextSeq 500. Both platforms identified all 7 of the synonymous mutations in the sample, while all 28 nonsynonymous mutations were identified from Oxford Nanopore and 20 nonsynonymous mutations were identified from Illumina.

A Synoptic Reporting System to Monitor Bone Marrow Aspirate and Biopsy Quality.

OBJECTIVES: Bone marrow evaluation plays a critical role in the diagnosis, staging, and monitoring of many diseases. Although there are standardized guidelines for assessing bone marrow specimen quality, there is a lack of evidence-based tools to perform such assessments. The objective was to monitor bone marrow sample quality in real time by standardizing the basic components of a synoptic report and incorporating it into a bone marrow report template. MATERIALS AND METHODS: A relational database of bone marrow quality parameters was developed and incorporated into our laboratory information system bone marrow report template, with data entry completed during specimen sign out. Data from multiple reports created within a date range were extracted by Structured Query Language query, and summarized in tabular form. Reports generated from these data were utilized in quality improvement efforts. RESULTS: The synoptic reporting system was routinely used to record the quality of bone marrow specimens from adult patients. Data from 3189 bone marrow aspirates, 3302 biopsies, and 3183 biopsy touch imprints identified hemodilution as the principal issue affecting bone marrow aspirate quality, whereas aspiration artifact and fragmentation affected bone marrow biopsy quality. CONCLUSIONS: The bone marrow synoptic reporting process was easy to use, readily adaptable, and has proved a useful component of the overall quality assurance process to optimize bone marrow quality.

Assessing acquired resistance to IDH1 inhibitor therapy by full-exon IDH1 sequencing and structural modeling.

Somatic mutations in hotspot regions of the cytosolic or mitochondrial isoforms of the isocitrate dehydrogenase gene (IDH1 and IDH2, respectively) contribute to the pathogenesis of acute myeloid leukemia (AML) by producing the oncometabolite 2-hydroxyglutarate (2-HG). The allosteric IDH1 inhibitor, ivosidenib, suppresses 2-HG production and induces clinical responses in relapsed/refractory IDH1-mutant AML. Herein, we describe a clinical case of AML in which we detected the neomorphic IDH1 p.R132C mutation in consecutive patient samples with a mutational hotspot targeted next-generation sequencing (NGS) assay. The patient had a clinical response to ivosidenib, followed by relapse and disease progression. Subsequent sequencing of the relapsed sample using a newly developed all-exon, hybrid-capture-based NGS panel identified an additional IDH1 p.S280F mutation known to cause renewed 2-HG production and drug resistance. Structural modeling confirmed that serine-to-phenylalanine substitution at this codon sterically hinders ivosidenib from binding to the mutant IDH1 dimer interface and predicted a similar effect on the pan-IDH inhibitor AG-881. Joint full-exon NGS and structural modeling enables monitoring IDH1 inhibitor-treated AML patients for acquired drug resistance and choosing follow-up therapy.