Hematologic presentation and the role of untargeted metabolomics analysis in monitoring treatment for riboflavin transporter deficiency.

Riboflavin transporter deficiency (RTD) (MIM #614707) is a neurogenetic disorder with its most common manifestations including sensorineural hearing loss, peripheral neuropathy, respiratory insufficiency, and bulbar palsy. Here, we present a 2-year-old boy whose initial presentation was severe macrocytic anemia necessitating multiple blood transfusions and intermittent neutropenia; he subsequently developed ataxia and dysarthria. Trio-exome sequencing detected compound heterozygous variants in SLC52A2 that were classified as pathogenic and a variant of uncertain significance. Bone marrow evaluation demonstrated megaloblastic changes. Notably, his anemia and neutropenia resolved after treatment with oral riboflavin, thus expanding the clinical phenotype of this disorder. We reiterate the importance of starting riboflavin supplementation in a young child who presents with macrocytic anemia and neurological features while awaiting biochemical and genetic work up. We detected multiple biochemical abnormalities with the help of untargeted metabolomics analysis associated with abnormal flavin adenine nucleotide function which normalized after treatment, emphasizing the reversible pathomechanisms involved in this disorder. The utility of untargeted metabolomics analysis to monitor the effects of riboflavin supplementation in RTD has not been previously reported.

Clinical performance of a semi-quantitative assay for SARS-CoV2 IgG and SARS-CoV2 IgM antibodies.

BACKGROUND: While the diagnosis of SARS-CoV-2 infection is primarily based on detection of viral RNA, the detection of SARS-CoV-2 antibodies is useful for assessing past prevalence of the disease, and in corroborating a current infection in challenging cases. Sensitive and specific immunoassays provide the ability to identify exposure to SARS-CoV-2, to determine seroconversion, to confirm eligibility for donation of convalescent plasma as well as play an essential part in epidemiological studies. We report on the validation of the Ansh Laboratories SARS-CoV-2 IgG and SARS-CoV-2 IgM ELISA immunoassays. These assays were evaluated for detection of anti-SARS-CoV-2 IgG and IgM antibodies for clinical use in our hospital as part of an orthogonal testing algorithm recommended by the CDC. METHODS: Diagnostic specificity and sensitivity of the IgG and IgM ELISA assays were tested using samples confirmed to be negative or positive for COVID-19 by RT-PCR. We also evaluated precision, analytical interference, and cross-reactivity with known cases of infection with other viruses. Additionally, we validated concordance with molecular and other serological testing and evaluated seroconversion in our patient population. RESULTS: The IgG and IgM ELISA assays showed acceptable precision, were robust to analytical interference and did not exhibit cross reactivity with specimens positive for common respiratory viruses. Both assays exhibited 95% agreement with a primary screening serological assay utilized at our institution as well as with a reference laboratory semi-quantitative method. Concordance with RT-PCR was excellent > 6 days after symptom onset (100%). CONCLUSIONS: The Ansh SARS-CoV-2 ELISA assays have good analytical performance suitable for clinical use.

A Rare Case of Pediatric Chronic Myelogenous Leukemia Presenting With Severe Thrombocytosis Without Leukocytosis.

Pediatric chronic myelogenous leukemia is uncommon. We report a pediatric patient with chronic myelogenous leukemia presenting with a normal white blood cell count and no circulating immature myeloid cells. The patient presented with extreme thrombocytosis (platelet count range: 2175-3064 × 109/L) noted incidentally. No splenomegaly was found. Examination of the bone marrow aspirate revealed normal cellularity and normal myeloid: erythroid ratio with marked megakaryocytic hyperplasia. Molecular studies on the bone marrow aspirate detected both the major BCR/ABL1 p210 fusion transcript (9280 copies; p210/ ABL1 ratio: 38.2%) and the minor p190 transcript (below limit of quantitation). The platelet count normalized within 2 weeks after treatment with the second-generation tyrosine kinase inhibitor dasatinib. Follow-up after 3 months revealed a 1.87 log reduction in p210 transcripts compared to diagnosis and no detectable p190 transcripts. This case highlights the need to include BCR/ABL1 fusion testing to accurately diagnose pediatric patients presenting with isolated thrombocytosis.