ABSTRACT
INTRODUCTION: In the era of next-generation sequencing, clinicians frequently encounter variants of unknown significance (VUS) in genetic testing. VUS may be reclassified over time as genetic knowledge grows. We know little about how best to approach VUS in the maturity-onset diabetes of the young (MODY). Therefore, our study aimed to determine the utility of reanalysis of previous VUS results in genetic confirmation of MODY. METHODS: A single-center retrospective chart review identified 85 subjects with a MODY clinical diagnosis. We reanalyzed genetic testing in 10 subjects with 14 unique VUS on MODY genes that was performed >3 years before the study. Demographic, clinical, and biochemical data was collected for those individuals. RESULTS: After reanalysis, 43% (6/14) of the gene variants were reclassified to a different category: 7% (1/14) were "likely pathogenic" and 36% (5/14) were "benign" or "likely benign." The reclassified pathogenic variant was in HNF1A and all reclassified benign variants were in HNF1A, HNF1B and PDX1. The median time between MODY testing and reclassification was 8 years (range: 4-10 years). CONCLUSION: In sum, iterative reanalyzing the genetic data from VUS found during MODY testing may provide high-yield diagnostic information. Further studies are warranted to identify the optimal time and frequency for such analyses.
ABSTRACT
OBJECTIVES: Thyroid storm (TS) is an uncommon but severe manifestation of hyperthyroidism and an endocrine emergency, as it is fatal if it goes unrecognized. In pediatrics, the current literature is limited to case reports and case series. Current knowledge is extrapolated from adult data. This systematic review aims to present the epidemiology, most common etiologies, clinical presentation, and most accepted standard of care of TS in children. We aim to raise awareness of hyperthyroidism in the pediatric community. CONTENT: The databases used were PubMed, google scholar, and LILACS, with the search terms "thyroid storm" AND "pediatrics". Studies included case reports and case series in English and Spanish from patients between the ages of 0-21 years with clinical features consistent with a diagnosis of TS based on ATA 2016, with or without reported scale scores, published between 2000 and 2022. Variables such as ethnicity, etiology, possible triggers, clinical features, and management components were analyzed and presented. SUMMARY: We analyzed data from 45 patients. Their mean age was 11.25 years. The majority of them were from Asia (26%). The most common clinical features were sinus tachycardia (86.7%) and fever (64%), followed by altered mental status (46%) and diarrhea (31%). Graves' disease was the most common underlying condition, and infection the most common precipitant. Thirty one percent of patients received treatment with four components; however morbidity and mortality were not clinically significant with those who did not. TS has a heterogeneous presentation with multisystemic involvement. The most common symptoms in this review were fever, tachycardia, diarrhea, and altered mental status. OUTLOOK: Further studies may be needed to best standardize the diagnosis and management of TS in children. Qualitative studies are needed to best assess the delay in diagnosis of hyperthyroidism and how this may impact prognosis in case patients were to develop TS.
